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Protein Tyrosine Kinase

Screening of epidermal growth factor receptor inhibitors in natural products by capillary electrophoresis combined with high performance liquid chromatography-tandem mass spectrometry

1 | Oct 09 2019

Li F et al. demonstrated a significant merit of our method in the identification of the bioactive compounds in natural products. [Read the Full Post]

Multicellular gene network analysis identifies a macrophage-related gene signature predictive of therapeutic response and prognosis of gliomas

2 | Oct 08 2019

Sun X et al. identified macrophage-related gene signature has good prognostic value for predicting resistance to targeted therapeutics and survival of glioma patients, implying that combining current targeted therapies with new macrophage-targeted therapy may be beneficial for the long-term treatment outcomes of glioma patients. [Read the Full Post]

BIBW2992, an irreversible EGFR/HER2 inhibitor highly effective in preclinical lung cancer models

41 | Oct 05 2019

Li D et al. showed that BIBW2992, an anilino-quinazoline designed to irreversibly bind EGFR and HER2, potently suppresses the kinase activity of wild-type and activated EGFR and HER2 mutants, including erlotinib-resistant isoforms. Consistent with this activity, BIBW2992 suppresses transformation in isogenic cell-based assays, inhibits survival of cancer cell lines and induces tumor regression in xenograft and transgenic lung cancer models, with superior activity over erlotinib. These findings encourage further testing of BIBW2992 in lung cancer patients harboring EGFR or HER2 oncogenes. [Read the Full Post]

Lapatinib Resistance in Breast Cancer Cells Is Accompanied by Phosphorylation-Mediated Reprogramming of Glycolysis

16 | Oct 01 2019

Ruprecht B et al. offered deeper perspectives on cancer drug resistance and suggests new biomarkers and treatment options for lapatinib-resistant cancers. [Read the Full Post]

Discovery of OSI-906: a selective and orally efficacious dual inhibitor of the IGF-1 receptor and insulin receptor

7 | Sep 29 2019

Mulvihill MJ et al. showed that OSI-906 is a novel, potent, selective and orally bioavailable dual IGF-1R/IR kinase inhibitor with favorable preclinical drug-like properties, which has demonstrated in vivo efficacy in tumor models and is currently in clinical testing. [Read the Full Post]

Overcoming Linsitinib intrinsic resistance through inhibition of nuclear factor-κB signaling in esophageal squamous cell carcinoma

8 | Sep 26 2019

Wu J et al. demonstrated that the intrinsic resistance to Linsitinib was predominantly mediated by NF-κB activation in ESCC. Moreover, combination of Linsitinib and JSH-23 as therapy provides a novel strategy to overcome resistance to Linsitinib in ESCC. [Read the Full Post]

Ponatinib (AP24534), a multitargeted pan-FGFR inhibitor with activity in multiple FGFR-amplified or mutated cancer models

35 | Sep 23 2019

Gozgit JM et al. showed that ponatinib is a potent pan-FGFR inhibitor and provide strong rationale for its evaluation in patients with FGFR-driven cancers. [Read the Full Post]

E7080 (lenvatinib), a multi-targeted tyrosine kinase inhibitor, demonstrates antitumor activities against colorectal cancer xenografts

0 | Sep 22 2019

Wiegering A et al. suggested antiangiogenic activity of E7080 at a dosage that was well tolerated by nude mice. E7080 may provide therapeutic benefits in the treatment of CRC with mutated KRAS. [Read the Full Post]

Cabozantinib (XL184), a novel MET and VEGFR2 inhibitor, simultaneously suppresses metastasis, angiogenesis, and tumor growth

17 | Sep 15 2019

Yakes FM et al. suggested that cabozantinib is a promising agent for inhibiting tumor angiogenesis and metastasis in cancers with dysregulated MET and VEGFR signaling. [Read the Full Post]

Effective combinatorial immunotherapy for castration-resistant prostate cancer

0 | Sep 15 2019

Lu X et al. illuminated a clinical path hypothesis for combining immune checkpoint blockade with MDSC-targeted therapies in the treatment of mCRPC. [Read the Full Post]

Axl Blockade by BGB324 Inhibits BCR-ABL Tyrosine Kinase Inhibitor-Sensitive and -Resistant Chronic Myeloid Leukemia

9 | Sep 14 2019

Erdmann R et al. showed that Axl inhibition has therapeutic potential in BCR-ABL TKI-sensitive as well as -resistant CML and support the need for clinical trials. [Read the Full Post]

ZD1839 (Iressa): an orally active inhibitor of epidermal growth factor signaling with potential for cancer therapy

27 | Sep 03 2019

Wakeling AE et al. indicated the potential utility of ZD1839 in the treatment of many human tumors and indicate that continuous once-a-day p.o. dosing might be a suitable therapeutic regimen. [Read the Full Post]

Brief Report: Rapid Acquisition of Alectinib Resistance in ALK-positive Lung Cancer with High Tumor Mutation Burden

26 | Aug 16 2019

Makimoto G et al. found that high TMB and heterogeneous tumor evolution might be responsible for rapid acquisition of alectinib resistance. [Read the Full Post]

Gefitinib Versus Gefitinib Plus Pemetrexed and Carboplatin Chemotherapy in EGFR-Mutated Lung Cancer

30 | Aug 15 2019

Noronha V et al. found that adding pemetrexed and carboplatin chemotherapy to gefitinib significantly prolonged PFS and OS but increased toxicity in patients with NSCLC. [Read the Full Post]

Yiqi Chutan Tang Reduces Gefitinib-Induced Drug Resistance in Non-Small-Cell Lung Cancer by Targeting Apoptosis and Autophagy

29 | Aug 15 2019

Zhang J et al. provided a new treatment strategy for patients with EGFR-TKI resistance in NSCLC. [Read the Full Post]

Treatment Patterns in Patients with Chronic-Phase Chronic Myeloid Leukaemia in Routine Clinical Practice: the SIMPLICITY Italian Population

126 | Aug 10 2019

Abruzzese E et al. provided valuable insights into management and treatment patterns in Italian patients with CML within routine clinical practice. [Read the Full Post]

PF-06463922 is a potent and selective next-generation ROS1/ALK inhibitor capable of blocking crizotinib-resistant ROS1 mutations

60 | Aug 05 2019

Zou HY et al. indicated that PF-06463922 has potential for treating ROS1 fusion-positive cancers, including those requiring agents with CNS-penetrating properties, as well as for overcoming crizotinib resistance driven by ROS1 mutation. [Read the Full Post]

Phase Ib study of the combination of pexidartinib (PLX3397), a CSF-1R inhibitor, and paclitaxel in patients with advanced solid tumors

31 | Aug 03 2019

Wesolowski R et al. showed the combination of pexidartinib and paclitaxel was generally well tolerated. RP2D for pexidartinib was 1600 mg/day. Pexidartinib blocked CSF-1R signaling, indicating potential for mitigating macrophage tumor infiltration. [Read the Full Post]

Overcoming Acquired Resistance to AZD9291, A Third-Generation EGFR Inhibitor, through Modulation of MEK/ERK-Dependent Bim and Mcl-1 Degradation

43 | Jul 25 2019

Shi P et al. showed that modulation of MEK/ERK-dependent Bim and Mcl-1 degradation critically mediates sensitivity and resistance of EGFR-mutant NSCLC cells to AZD9291 and hence is an effective strategy to overcome acquired resistance to AZD9291. [Read the Full Post]

Sustained inhibition of receptor tyrosine kinases and macrophage depletion by PLX3397 and rapamycin as a potential new approach for the treatment of MPNSTs

27 | Jul 18 2019

Patwardhan PP et al. suggested that PLX3397 is superior to imatinib in the treatment of MPNSTs, and the combination of PLX3397 with a TORC1 inhibitor could provide a new therapeutic approach for the treatment of this disease. [Read the Full Post]

The Bruton tyrosine kinase inhibitor PCI-32765 blocks B-cell activation and is efficacious in models of autoimmune disease and B-cell malignancy

34 | Jul 16 2019

Honigberg LA et al. support Btk inhibition as a therapeutic approach for the treatment of human diseases associated with activation of the BCR pathway. [Read the Full Post]

A high-performance liquid chromatography-tandem mass spectrometry method for the determination of lifrafenib, a novel RAF kinase and EGFR inhibitor, in human plasma and urine and its application in clinical pharmacokinetic study

62 | Jul 01 2019

Yao X et al. showed robust and sensitive, it successfully fulfilled the requirement of clinical pharmacokinetic study of lifirafenib in Chinese patients with locally advanced or metastatic solid tumors. [Read the Full Post]

First-in-Human Phase I Study of the Selective MET Inhibitor, Savolitinib, in Patients with Advanced Solid Tumors: Safety, Pharmacokinetics, and Antitumor Activity

29 | Jun 30 2019

Gan HK et al. showed the tolerability profile of savolitinib was acceptable and the RP2D was established as 600 mg QD. Preliminary antitumor activity was demonstrated supporting further study in patients with PRCC. [Read the Full Post]

Fibroblast Growth Factor Receptor 4 Targeting in Cancer: New Insights into Mechanisms and Therapeutic Strategies

40 | Jun 28 2019

Lang L et al. indicated their aim is to pinpoint the potential of FGFR4 as a therapeutic target and identify new avenues for advancing future research in the field. [Read the Full Post]

TKI-Related Platelet Dysfunction Does Not Correlate With Bleeding in Patients With Chronic Phase-Chronic Myeloid Leukemia With Complete Hematological Response

107 | Jun 21 2019

Sener Y et al. concluded that TKIs may impair in vitro platelet aggregation but this impairment is not associated with bleeding diathesis. [Read the Full Post]

Simultaneous Inhibition of EGFR and HER2 via Afatinib Augments the Radiosensitivity of Nasopharyngeal Carcinoma Cells

98 | Jun 18 2019

Huang F et al. indicated the potential of repositioning afatinib or other ERBB-family-targeted agents for improving radiation response in NPC cells. [Read the Full Post]

Discovery of Brigatinib (AP26113), a Phosphine Oxide-Containing, Potent, Orally Active Inhibitor of Anaplastic Lymphoma Kinase

135 | Jun 12 2019

Huang WS et al. showed that brigatinib represents the most clinically advanced phosphine oxide-containing drug candidate to date and is currently being evaluated in a global phase 2 registration trial. [Read the Full Post]

NK92-CD16 cells are cytotoxic to non-small cell lung cancer cell lines that have acquired resistance to tyrosine kinase inhibitors

143 | Jun 08 2019

Park HR et al. suggested that combinational treatment with NK cell-based immunotherapy and cetuximab may be promising for patients with TKI-resistant NSCLC. [Read the Full Post]

Inhibition of colony-stimulating-factor-1 signaling in vivo with the orally bioavailable cFMS kinase inhibitor GW2580

39 | Jun 04 2019

Conway JG et al. showed that GW2580's selective inhibition of monocyte growth and bone degradation is consistent with cFMS kinase inhibition. The ability of GW2580 to chronically inhibit CSF-1 signaling through cFMS kinase in normal and tumor cells in vivo makes GW2580 a useful tool in assessing the role of cFMS kinase in normal and disease processes. [Read the Full Post]

ASP2215 in the treatment of relapsed/refractory acute myeloid leukemia with FLT3 mutation: background and design of the ADMIRAL trial

124 | Jun 02 2019

Gorcea CM et al. showed that ASP2215 (gilteritinib) is a novel, dual FLT3/AXL inhibitor with promising early phase trial data (NCT02014558). [Read the Full Post]

Lorlatinib in non-small-cell lung cancer with ALK or ROS1 rearrangement: an international, multicentre, open-label, single-arm first-in-man phase 1 trial

99 | May 07 2019

Shaw AT et al. indicated lorlatinib might be an effective therapeutic strategy for patients with ALK-positive NSCLC who have become resistant to currently available TKIs, including second-generation ALK TKIs, and is being investigated in a phase 3 randomised controlled trial comparing lorlatinib to crizotinib (ClinicalTrials.gov, NCT03052608). [Read the Full Post]

Integrated analysis of multiple receptor tyrosine kinases identifies Axl as a therapeutic target and mediator of resistance to sorafenib in hepatocellular carcinoma

66 | Apr 24 2019

Pinato DJ et al. found that suppression of Axl-dependent signalling influences the transformed phenotype in HCC cells and contributes to adaptive resistance to sorafenib, providing a pre-clinical rationale for the development of Axl inhibitors as a measure to overcome sorafenib resistance. [Read the Full Post]

Favorable predictors for survival in advanced ALK-positive non-small cell lung cancer patients beyond crizotinib resistance

144 | Apr 24 2019

Xu H et al. found that long PFS with crizotinib (≥10.4 months), intracranial progression, and use of next-generation ALK inhibitors might be favorable predictors for OS in advanced ALK-positive NSCLC patients. [Read the Full Post]

lncRNA MIR100HG-derived miR-100 and miR-125b mediate cetuximab resistance via Wnt/β-catenin signaling

0 | Apr 10 2019

Lu Y et al. described a double-negative feedback loop between MIR100HG and the transcription factor GATA6, whereby GATA6 represses MIR100HG, but this repression is relieved by miR-125b targeting of GATA6. These findings identify a clinically actionable, epigenetic cause of cetuximab resistance. [Read the Full Post]

Ibrutinib for the treatment of chronic lymphocytic leukemia

138 | Mar 30 2019

Novel, extremely promising, combination strategies, based on the association of ibrutinib with chemoimmunotherapy, antiCD20 monoclonal antibody or other targeted agents, are currently being investigated, with the goal of achieving greater depth of remission, especially MRD-negativity, and removing the need for indefinite treatment. [Read the Full Post]

Lenvatinib versus placebo in radioiodine-refractory thyroid cancer

145 | Mar 25 2019

Schlumberger M et al. indicated that Lenvatinib, as compared with placebo, was associated with significant improvements in progression-free survival and the response rate among patients with iodine-131-refractory thyroid cancer. Patients who received lenvatinib had more adverse effects. [Read the Full Post]

E7080 (lenvatinib), a multi-targeted tyrosine kinase inhibitor, demonstrates antitumor activities against colorectal cancer xenografts

134 | Mar 25 2019

Wiegering A et al. suggested antiangiogenic activity of E7080 at a dosage that was well tolerated by nude mice. E7080 may provide therapeutic benefits in the treatment of CRC with mutated KRAS. [Read the Full Post]

Safety and Efficacy Profile of Neratinib: A Systematic Review and Meta-Analysis of 23 Prospective Clinical Trials

200 | Mar 20 2019

Tao Z et al. demonstrated that neratinib provides a benefit in survival outcome. When combined with other anticancer agents, neratinib may hold promise for treating breast cancer with central nervous system metastases. [Read the Full Post]

Neratinib after trastuzumab-based adjuvant therapy in HER2-positive breast cancer (ExteNET): 5-year analysis of a randomised, double-blind, placebo-controlled, phase 3 trial

219 | Mar 19 2019

Martin M et al. showed that at the 5-year follow-up, 1 year of extended adjuvant therapy with neratinib, administered after chemotherapy and trastuzumab, significantly reduced the proportion of clinically relevant breast cancer relapses-ie, those that might lead to death, such as distant and locoregional relapses outside the preserved breast-without increasing the risk of long-term toxicity. An analysis of overall survival is planned after 248 events. [Read the Full Post]

A Genome-Wide CRISPR Screen Identifies Genes Critical for Resistance to FLT3 Inhibitor AC220

163 | Mar 07 2019

Hou P et al. identified novel genes whose loss of function conferred resistance to a selective FLT3 inhibitor, providing new insight into signaling pathways that contribute to acquired resistance in AML. [Read the Full Post]

Quizartinib (AC220) reverses ABCG2-mediated multidrug resistance: In vitro and in vivo studies

125 | Mar 05 2019

Li J et al. demonstrated that quizartinib potentiates the antineoplastic activity of wild-type and R482T mutant ABCG2 substrates. These findings may be useful in clinical practice for cancer combination therapy with quizartinib. [Read the Full Post]

Risk of anastomotic dehiscence in patients with pulmonary fibrosis transplanted while receiving anti-fibrotics: Experience of the Australian Lung Transplant Collaborative

213 | Mar 04 2019

Mackintosh JA et al. showed the incidence of bronchial dehiscence after transplantation for IPF is low and is not significantly higher in patients receiving anti-fibrotic therapy at the time of transplantation. [Read the Full Post]

Efficacy of BIBF 1120 or BIBF 1120 plus chemotherapy on nasopharyngeal carcinoma in vitro and in vivo

184 | Mar 04 2019

Xue C et al. indicated that BIBF 1120 administered in conjunction with chemotherapy might provide an effective treatment method for NPC. [Read the Full Post]

Microglial modulation through colony-stimulating factor-1 receptor inhibition attenuates demyelination

76 | Feb 25 2019

Wies Mancini VSB et al. showed that BLZ945 induced a significant reduction in the number of microglia. Preventive BLZ945 treatment attenuated demyelination in the acute CPZ model, mainly in cortex and external capsule. In contrast, BLZ945 treatment in the acute CPZ model failed to protect myelin or foster remyelination in myelin-rich areas, which may respond to a loss in microglial phagocytic capacity and the consequent impairment in oligodendroglial differentiation. Preventive and therapeutic BLZ945 treatment promoted remyelination and neuroprotection in the chronic model. These results could be potentially transferred to the treatment of progressive forms of MS. [Read the Full Post]

Design and molecular modeling of novel P38α MAPK inhibitors targeting breast cancer, synthesized from oxygen heterocyclic natural compounds

646 | Feb 24 2019

Abdelhafez OM et al. indicated these promising results of cytotoxic activity and significant inhibition of p38α MAP kinase, were confirmed by exploring the effect of benzofuran derivative (18) on the apoptotic induction and cell cycle progression of MCF-7 cell line. Compound 18 induced preG1 apoptosis and cell growth arrest at G2/M phase preventing the mitotic cycle. Moreover it activated the caspase-7 which executes apoptosis. Molecular docking study was carried out using GOLD program to predict the mode of binding interaction of the synthesized compounds into the target p38α MAPK. Additionally, the physicochemical properties and ADME parameters of compound 18 were examined in silico to investigate its drug-likeness. [Read the Full Post]

Crenolanib is a selective type I pan-FLT3 inhibitor

151 | Feb 21 2019

Smith CC et al. showed that Crenolanib has significant promise for achieving deep and durable responses in FLT3-mutant AML, and may have a profound impact upon future medicinal chemistry efforts in oncology. [Read the Full Post]

Practice patterns and outcomes with the use of regorafenib in metastatic colorectal cancer: Results from the Regorafenib in Metastatic colorectal cancer - An Indian exploratory analysis study

239 | Feb 19 2019

Ramaswamy A et al. indicated duration of treatment with regorafenib as an efficacy end point in this study is similar to available data from other regions as it is the side effect profile. [Read the Full Post]

Regorafenib for patients with hepatocellular carcinoma who progressed on sorafenib treatment (RESORCE): a randomised, double-blind, placebo-controlled, phase 3 trial

231 | Feb 18 2019

Bruix J et al. indicated that regorafenib is the only systemic treatment shown to provide survival benefit in HCC patients progressing on sorafenib treatment. Future trials should explore combinations of regorafenib with other systemic agents and third-line treatments for patients who fail or who do not tolerate the sequence of sorafenib and regorafenib. [Read the Full Post]

Vascular Endothelial Growth Factor-A Increases the Aqueous Humor Outflow Facility

0 | Feb 10 2019

Fujimoto T et al. suggested that VEGF-A may regulate the conventional aqueous outflow of SCE cells through VEGFR2. [Read the Full Post]

Fatty acid translocase promoted hepatitis B virus replication by upregulating the levels of hepatic cytosolic calcium

205 | Feb 06 2019

Huang J et al. identified a novel link between CD36 and HBV replication, which is associated with cytosolic calcium and the Src kinase pathway. [Read the Full Post]

The energy sensing LKB1-AMPKα1 pathway regulates IGF1 secretion and consequent activation of the IGF1R-PKB pathway in primary hepatocytes

96 | Feb 06 2019

Chen L et al. demonstrated that the energy-sensing LKB1-AMPK pathway regulates IGF1 secretion in mouse primary hepatocytes, which in turn regulates activation of the IGF1R-PKB pathway. [Read the Full Post]

Pharmacology and pharmacokinetics of imatinib in pediatric patients

399 | Jan 22 2019

Suttorp M et al. indicated that adherence to imatinib intake may be the most prominent factor influencing treatment outcome in teenagers thus pointing towards the potential benefits of regular drug monitoring. [Read the Full Post]

Pharmacology and pharmacokinetics of imatinib in pediatric patients

0 | Jan 22 2019

Suttorp M et al. indicated taht pharmacokinetic variables (e.g. alpha 1-acid glycoprotein binding, drug-drug/food-drug interactions via cytochrome P450 3A4/5, cellular uptake mediated via OCT-1-influx variations and P-glycoprotein-mediated drug efflux) still await to be addressed in pediatric patients systematically. [Read the Full Post]

A randomized, open-label study of the efficacy and safety of AZD4547 monotherapy versus paclitaxel for the treatment of advanced gastric adenocarcinoma with FGFR2 polysomy or gene amplification

260 | Jan 15 2019

Van Cutsem E et at. indicated that AZD4547 did not significantly improve PFS versus paclitaxel in gastric cancer FGFR2 amplification/polysomy patients. Considerable intratumor heterogeneity for FGFR2 gene amplification and poor concordance between FGFR2 amplification/polysomy and FGFR2 expression indicates the need for alternative predictive biomarker testing. AZD4547 was generally well tolerated. [Read the Full Post]

The c.1085A>G Genetic Variant of CSF1R Gene Regulates Tumor Immunity by Altering the Proliferation, Polarization, and Function of Macrophages

142 | Nov 26 2018

Yeh YM et al. indicated that CSF1R c.1085A>G genetic variant regulates tumor immunity by altering the polarization and function of macrophages. This genetic variant confers the sensitivity to CSF-1R inhibitors, implying as a biomarker in targeting CSF-1R signaling for cancer treatment. [Read the Full Post]

Host Serine/Threonine Kinases mTOR and Protein Kinase C-α Promote InlB-Mediated Entry of Listeria monocytogenes

1904 | Nov 21 2018

Bhalla M et al. identified mTOR and PKC-α to be host factors exploited by Listeria to promote infection. PKC-α controls Listeria entry, at least in part, by regulating the actin cytoskeleton downstream of the Met receptor. [Read the Full Post]

The Aryl Hydrocarbon Receptor Governs Epithelial Cell Invasion during Oropharyngeal Candidiasis

243 | Nov 16 2018

Solis NV et al. indicated that AhR plays a central role in governing the pathogenic interactions of C. albicans with oral epithelial cells during OPC and suggested that this receptor is a potential therapeutic target [Read the Full Post]

The radiosensitizing effect of the aurora kinase inhibitors, ENMD-2076, on canine mast cell tumours in vitro

553 | Nov 13 2018

Shiomitsu K et al. suggested the potential usefulness of treating canine mast cell tumours with aurora kinase inhibitors alone or in conjunction with radiation therapy. [Read the Full Post]

Cell-based assay system for high-throughput screening of anti-photo-aging agents in fibroblast transfectants

567 | Nov 11 2018

Lee S et al indicated that sclareol attenuated UVB-induced photo-aging by an increase in collagen synthesis and decrease in MMP-1 activity. [Read the Full Post]

Interleukin 37 limits monosodium urate crystal-induced innate immune responses in human and murine models of gout

182 | Nov 09 2018

Liu L et al. revealed that IL-37 limits runaway inflammation initiated by MSU crystal-induced immune responses, partly in a Mertk-dependent fashion. Thus, rhIL-37 has both preventive and therapeutic effects in gouty arthritis. [Read the Full Post]

Dying glioma cells establish a proangiogenic microenvironment through a caspase 3 dependent mechanism

435 | Nov 07 2018

Feng X et al. illustrated that caspase 3 activation in dying glioma cells unfavorably supported post-irradiation angiogenesis. This double-edged role of caspase 3 suggested that taming caspase 3 from the opposite side, not always activating it, may provide novel therapeutic strategies due to restricted post-irradiation angiogenesis. [Read the Full Post]

The afatinib resistance of in vivo generated H1975 lung cancer cell clones is mediated by SRC/ERBB3/c-KIT/c-MET compensatory survival signaling

0 | Nov 07 2018

Booth L et al. indicated that inhibition of ERBB3 signaling via both blockade of SRC and ERBB1 results in tumor cell death. [Read the Full Post]

Pro-survival signal inhibition by CDK inhibitor dinaciclib in Chronic Lymphocytic Leukaemia

0 | Nov 06 2018

Chen Y et al. showed that dinaciclib targets multiple pro-survival signalling pathways in CLL, which provides a mechanistic explanation for its potent induction of apoptosis. They also support a therapeutic application of cyclin-dependent kinase inhibitors in CLL in combination with other relevant targeted therapies. [Read the Full Post]

Vascular Endothelial Growth Factor-A Increases the Aqueous Humor Outflow Facility

467 | Nov 06 2018

Fujimoto T et al. suggested that VEGF-A may regulate the conventional aqueous outflow of SCE cells through VEGFR2. [Read the Full Post]

No preclinical rationale for IGF1R directed therapy in chondrosarcoma of bone

0 | Nov 04 2018

Peterse EF et al. indicated that the IGF pathway is not essential for chondrosarcoma growth, migration or chemoresistance. Furthermore, IGF1R is only minimally expressed in chondrosarcoma primary tumours. Therefore, the IGF pathway is not expected to be an effective therapeutic target for chondrosarcoma of bone. [Read the Full Post]

Steroid hormone 20-hydroxyecdysone promotes higher calcium mobilization to induce apoptosis

290 | Oct 31 2018

Wang D et al. suggested that 20E and JH via different pathways regulate calcium mobilization and homeostasis at different levels, thus inform different gene expression and cellular responses. [Read the Full Post]

Relaxing Effect of TSU-68, an Antiangiogenic Agent, on Mouse Airway Smooth Muscle

268 | Oct 30 2018

Tan H et al. indicated that TSU-68 relaxes tense ASM by reducing the intracellular Ca2+ concentration through blocking VDCCs and NSCCs, which suggested that this small molecule might be useful in the treatment of abnormal smooth muscle. [Read the Full Post]

MET amplification and epithelial-to-mesenchymal transition exist as parallel resistance mechanisms in erlotinib-resistant, EGFR-mutated, NSCLC HCC827 cells

181 | Oct 27 2018

Jakobsen KR et al. showed that parallel resistance mechanisms appear during erlotinib-resistance development in EGFR-mutated NSCLC cells and highlight a role for FGFR1 expression changes as an early response to erlotinib as well as a bypass-signaling mechanism. [Read the Full Post]

Construction of a novel cell-based assay for the evaluation of anti-EGFR drug efficacy against EGFR mutation

0 | Oct 25 2018

Hoshi H et al. successfully developed a novel cell-based assay for evaluating the efficacy of anti-EGFR drugs against EGFR mutation. [Read the Full Post]

Diverse drug-resistance mechanisms can emerge from drug-tolerant cancer persister cells

404 | Oct 25 2018

Ramirez M et al. found that the drug-tolerant persister state does not limit--and may even provide a latent reservoir of cells for--the emergence of heterogeneous drug-resistance mechanisms. [Read the Full Post]

Three-dimensional biomimetic model to reconstitute sprouting lymphangiogenesis in vitro

257 | Oct 23 2018

Kim S et al. not only revealed critical but unappreciated role of mechanical cue that regulates lymphangiogenic sprouting, but also provides a novel biomimetic model that may leverage further biological studies as well as phenotypic drug screening. [Read the Full Post]

Construction of a novel cell-based assay for the evaluation of anti-EGFR drug efficacy against EGFR mutation

681 | Oct 20 2018

Hoshi H et al. successfully developed a novel cell-based assay for evaluating the efficacy of anti-EGFR drugs against EGFR mutation. [Read the Full Post]

PDE5 inhibitors enhance the lethality of [pemetrexed + sorafenib]

519 | Oct 19 2018

Booth L et al. argued that additional clinical studies combining pemetrexed, sorafenib and sildenafil are warranted. [Read the Full Post]

Tumor-secreted anterior gradient-2 binds to VEGF and FGF2 and enhances their activities by promoting their homodimerization.

418 | Oct 18 2018

Guo H et al. proposed that the secreted AGR2 is a blockable molecular target, which acts as a chaperon-like enhancer to VEGF and FGF2. [Read the Full Post]

Resistance to RET-Inhibition in RET-Rearranged NSCLC Is Mediated By Reactivation of RAS/MAPK Signaling

841 | Oct 12 2018

Nelson-Taylor SK et al. demonstrated that resistance to ponatinib in RET-rearranged lung adenocarcinoma is mediated by bypass signaling mechanisms that result in restored RAS/MAPK activation. [Read the Full Post]

Targeting Hsp90 with FS-108 circumvents gefitinib resistance in EGFR mutant non-small cell lung cancer cells

220 | Oct 10 2018

Wang YQ et al. indicated that FS-108 is a powerful agent that impacts the survival of gefitinib-resistant cells in vitro and in vivo through targeting Hsp90. [Read the Full Post]

Cyclic tensile strain promotes the osteogenic differentiation of a bone marrow stromal cell and vascular endothelial cell co-culture system

469 | Oct 08 2018

Jiang Y et al. demonstrated that cyclic tensile strain promotes osteogenic differentiation in BMSC/VEC co-culture systems, possibly via a VEC-mediated paracrine effect of VEGF on BMSCs. [Read the Full Post]

Efficient extravasation of tumor-repopulating cells depends on cell deformability

282 | Sep 30 2018

Chen J et al. suggested that tumor cell deformability is a key factor in controlling extravasation dynamics during metastasis. [Read the Full Post]

Pre-Osteoblasts Stimulate Migration of Breast Cancer Cells via the HGF/MET Pathway

235 | Sep 28 2018

Vallet S et al. demonstrated for the first time a role for pre-OBs in mediating HGF/MET- dependent migration of BC cells and strongly support the clinical evaluation of INCB28060 and other MET inhibitors to limit and/or prevent BC-associated bone metastases. [Read the Full Post]

Anti-Invasive and Anti-Proliferative Synergism between Docetaxel and a Polynuclear Pd-Spermine Agent

395 | Sep 27 2018

Batista de Carvalho AL et al. aimed at the application of these combined strategies towards metastatic breast cancer (or other type of resistant cancers), justifying further studies that include pre-clinical trials. [Read the Full Post]

RAD51 inhibition in triple negative breast cancer cells is challenged by compensatory survival signaling and requires rational combination therapy

0 | Sep 25 2018

Wiegmans AP et al. highlight a potential compensatory mechanism via p38 that limits DNA targeted therapy. [Read the Full Post]

Lassa Virus Cell Entry via Dystroglycan Involves an Unusual Pathway of Macropinocytosis

0 | Sep 25 2018

Oppliger J et al. revealed novel fundamental aspects of the LASV-host cell interaction and highlights a possible candidate drug target for therapeutic intervention. [Read the Full Post]

Cholesterol Synthetase DHCR24 Induced by Insulin Aggravates Cancer Invasion and Progesterone Resistance in Endometrial Carcinoma

0 | Sep 24 2018

Dai M et al. demonstrated for the first time the crucial role of the insulin/STAT3/DHCR24/PGR axis in the progression of EC by modulating the metastasis and progesterone response, which could serve as potential therapeutic targets for the treatment of EC with progesterone receptor loss. [Read the Full Post]

Antibiotic drug tigecycline reduces neuroblastoma cells proliferation by inhibiting Akt activation in vitro and in vivo

364 | Aug 24 2018

Zhong X et al. supported by previous studies concerning the application of tigecycline in human tumors treatment, suggesting that tigecycline might act as a potential candidate agent for neuroblastoma treatment. [Read the Full Post]

Activation of the IGF1R pathway potentially mediates acquired resistance to mutant-selective 3rd-generation EGF receptor tyrosine kinase inhibitors in advanced non-small cell lung cancer

291 | Aug 23 2018

Park JH et al. suggested that activation of the IGF1R pathway associated with IGFBP3 loss can induce an acquired resistance to the mutant-selective EGFR-TKI, WZ4002. Therefore, a combined therapy of IGF1R inhibitors and mutant-selective EGFR-TKIs might be a viable treatment strategy for overcoming acquired resistance. [Read the Full Post]

FYN promotes breast cancer progression through epithelial-mesenchymal transition

0 | Aug 20 2018

Xie YG et al. found that FYN was overexpressed in breast cancer and overexpression of FYN promoted cell proliferation, migration and invasion in the MCF10A cells, whereas depletion of FYN suppressed cell proliferation, migration and invasion in the MDA-MB-231 cells. Moreover, FYN upregulated the expression of mesenchymal markers and epithelial-mesenchymal transition (EMT)-related transcription factors, and downregulated the expression of epithelial markers, suggesting that FYN induces EMT in breast cancer cells. Furthermore, FYN was transcriptionally regulated by FOXO1 and mediated FGF2-induced EMT through both the PI3K/AKT and ERK/MAPK pathways. [Read the Full Post]

Cotargeting MNK and MEK kinases induces the regression of NF1-mutant cancers

268 | Aug 15 2018

Lock R et al. demonstrated that combined MNK and MEK suppression represents a promising therapeutic strategy for these incurable Ras-driven tumors and highlight the utility of developing selective MNK inhibitors for these and possibly other malignancies. [Read the Full Post]

The cKit Inhibitor, Masitinib, Prevents Diabetes-Induced Retinal Vascular Leakage

579 | Aug 10 2018

Kim SR et al. provided the first demonstration that cKit inhibitors, such as masitinib, might be promising therapeutics for prevention of diabetes-induced breakdown of the BRB. [Read the Full Post]

Proliferation Markers Are Associated with MET Expression in Hepatocellular Carcinoma and Predict Tivantinib Sensitivity In Vitro

0 | Aug 10 2018

Rebouissou S et al. indicated that Tivantinib acts as an antimitotic compound, and cell proliferation markers are the best predictors of its antitumor efficacy in cell lines. Ki67 expression should be tested in clinical trials to predict tivantinib response. [Read the Full Post]

Local release of masitinib alters in vivo implantable continuous glucose sensor performance

424 | Aug 09 2018

Avula M et al. showed that the mast cell-targeting tyrosine kinase inhibitor, masitinib, was released from degradable polymer microspheres delivered from the surfaces of FDA-approved human commercial CGM needle-type implanted sensors in a rodent subcutaneous test bed. By targeting the mast cell c-Kit receptor and inhibiting mast cell activation and degranulation, local masitinib penetration around the CGM to several hundred microns sought to reduce sensor fibrosis to extend CGM functional lifetimes in subcutaneous sites. Drug-releasing and control CGM implants were compared in murine percutaneous implant sites for 21 days using direct-wire continuous glucose reporting. Drug-releasing implants exhibited no significant difference in CGM fibrosis at implant sites but showed relatively stable continuous sensor responses over the study period compared to blank microsphere control CGM implants. [Read the Full Post]

Metallothionein-1G facilitates sorafenib resistance through inhibition of ferroptosis

0 | Aug 09 2018

Sun X et al. showed that metallothionein (MT)-1G is a critical regulator and promising therapeutic target of sorafenib resistance in human HCC cells. [Read the Full Post]

JAK2 inhibition sensitizes resistant EGFR-mutant lung adenocarcinoma to tyrosine kinase inhibitors

651 | Aug 02 2018

Gao SP et al. revealed a mechanism whereby JAK2 inhibition overcomes acquired resistance to EGFR inhibitors and support the use of combination therapy with JAK and EGFR inhibitors for the treatment of EGFR-dependent NSCLC. [Read the Full Post]

Activation of the IGF1R pathway potentially mediates acquired resistance to mutant-selective 3rd-generation EGF receptor tyrosine kinase inhibitors in advanced non-small cell lung cancer

756 | Aug 01 2018

Park JH et al. suggested that activation of the IGF1R pathway associated with IGFBP3 loss can induce an acquired resistance to the mutant-selective EGFR-TKI, WZ4002. Therefore, a combined therapy of IGF1R inhibitors and mutant-selective EGFR-TKIs might be a viable treatment strategy for overcoming acquired resistance. [Read the Full Post]

A novel oncogenic BTK isoform is overexpressed in colon cancers and required for RAS-mediated transformation

531 | Jul 20 2018

Grassilli E et al. revealed that BTK, via p65BTK expression, is a novel and powerful oncogene acting downstream of the RAS/MAPK pathway and suggest that its targeting may be a promising therapeutic approach. [Read the Full Post]

BTK inhibition is a potent approach to block IgE-mediated histamine release in human basophils

395 | Jul 19 2018

Smiljkovic D et al. indicated that BTK-targeting drugs are potent inhibitors of IgE-dependent histamine release in human basophils. The clinical value of BTK inhibition in the context of allergic diseases remains to be determined. [Read the Full Post]

Src family kinases promote silencing of ATR-Chk1 signaling in termination of DNA damage checkpoint.

468 | Jul 07 2018

Fukumoto Y, et al. suggested a model according to which Src family kinases send a termination signal between the completion of DNA repair and the initiation of checkpoint termination. [Read the Full Post]

Genome-Wide Gene Expression Analysis Identifies the Proto-oncogene Tyrosine-Protein Kinase Src as a Crucial Virulence Determinant of Infectious Laryngotracheitis Virus in Chicken Cells

442 | Jul 01 2018

Li H et al. indicated that the results from our study advance our understanding of host-ILTV interactions on a molecular level and provide experimental evidence that it is possible to control ILT via the manipulation of host-virus interactions. [Read the Full Post]

Targeting Suppressive Myeloid Cells Potentiates Checkpoint Inhibitors to Control Spontaneous Neuroblastoma

0 | Jun 30 2018

Mao Y et al. demonstrated the essential role of CSF-1R signaling during the induction of suppressive myeloid cells and emphasize its clinical potential as an immunotherapy for human cancers. [Read the Full Post]

FcγRIIB mediates antigen-independent inhibition on human B lymphocytes through Btk and p38 MAPK

492 | Jun 29 2018

Tzeng SJ et al. found the importance of antigen-independent inhibition by FcγRIIB in the prevention from antibody-mediated autoimmune diseases and in the regulation of B cell homeostasis. [Read the Full Post]

EGF-mediated EGFR/ERK signaling pathway promotes germinative cell proliferation in Echinococcus multilocularis that contributes to larval growth and development

941 | Jun 08 2018

Cheng Z et al. demonstrated the contribution of EGF-mediated EGFR/ERK signaling to the regulation of germinative cells in E. multilocularis, and suggest the EGFR/ERK signaling as a potential therapeutic target for AE and perhaps other human cestodiasis. [Read the Full Post]

Cancer Cell-derived Exosomes Induce Mitogen-activated Protein Kinase-dependent Monocyte Survival by Transport of Functional Receptor Tyrosine Kinases

990 | May 28 2018

Song X et al. provided insights into the long sought question on monocyte survival prior to formation of plentiful TAMs in the tumor microenvironment. [Read the Full Post]

Cell-based approach for 3D reconstruction of lymphatic capillaries in vitro reveals distinct functions of HGF and VEGF-C in lymphangiogenesis

454 | May 14 2018

Gibot L et al. showed that fibroblast-derived VEGF-C and HGF cooperate in the formation of lymphatic vasculature by activating ERK1/2 signaling, and demonstrate distinct functions of HGF/c-Met and VEGF-C/VEGFR-3 in lymphangiogenesis. This lymphatic vascular construct is expected to facilitate studies of lymphangiogenesis in vitro and it holds promise as a strategy for regeneration of lymphatic vessels and treatment of lymphatic disorders in various conditions. [Read the Full Post]

miR-206 regulates cisplatin resistance and EMT in human lung adenocarcinoma cells partly by targeting MET

431 | May 14 2018

Chen QY et al. found that miR-206 could also sensitize A549/DDP cells to cisplatin in mice model. Taken together, our study implied that activation of miR-206 or inactivation of its target gene pathway could serve as a novel approach to reverse cisplatin resistance in lung adenocarcinomas cells. [Read the Full Post]

Therapeutic implication of HER2 in advanced biliary tract cancer

812 | May 10 2018

Nam AR et al. suggested that HER2 could be a therapeutic target, and that a HER2-targeting strategy should be developed further in patients with HER2-positive advanced BTC. [Read the Full Post]

Identification of different ALK mutations in a pair of neuroblastoma cell lines established at diagnosis and relapse

612 | May 02 2018

Chen L et al. showed that use both Sanger and targeted deep sequencing, this study describes the identification of distinct ALK mutations in these paired cell lines, including the rare R1275L mutation, which has not previously been reported in a neuroblastoma cell line. Analysis of the sensitivity of NBLW and NBLW-R cells to a panel of ALK inhibitors (TAE-684, Crizotinib, Alectinib and Lorlatinib) revealed differences between the paired cell lines, and overall NBLW-R cells with the F1174L mutation were more resistant to ALK inhibitor induced apoptosis compared with NBLW cells. This pair of cell lines represents a valuable pre-clinical model of clonal evolution of ALK mutations associated with neuroblastoma progression. [Read the Full Post]

A Receptor Tyrosine Kinase Inhibitor, Dovitinib (TKI-258), Enhances BMP-2-Induced Osteoblast Differentiation In Vitro

1677 | Apr 29 2018

Lee Y et al. suggested that dovitinib has a potent stimulating effect on BMP-2-induced osteoblast differentiation and this existing drug has potential for repositioning in the treatment of bone-related disorders. [Read the Full Post]

Traf2- and Nck-interacting kinase (TNIK) is involved in the anti-cancer mechanism of dovitinib in human multiple myeloma IM-9 cells

1251 | Apr 29 2018

Chon HJ et al. provided new evidence that TNIK may be involved in the proliferation of multiple myeloma IM-9 cells and in the anti-cancer activity of dovitinib via inhibition of the endogenous Wnt signaling pathway. [Read the Full Post]

Targeting Suppressive Myeloid Cells Potentiates Checkpoint Inhibitors to Control Spontaneous Neuroblastoma

448 | Apr 28 2018

Mao Y et al. demonstrated the essential role of CSF-1R signaling during the induction of suppressive myeloid cells and emphasize its [Read the Full Post]

PQ401, an IGF-1R inhibitor, induces apoptosis and inhibits growth, proliferation and migration of glioma cells

399 | Apr 26 2018

Zhou X et al. suggested that PQ401 may serve as a promising leading drug for treating glioma patients with elevated IGF-1R signalling. [Read the Full Post]

Mechanism for neurotropic action of vorinostat, a pan histone deacetylase inhibitor.

450 | Apr 24 2018

Shukla S et al. suggested that vorinostat exerts a positive effect on the neuritogenesis via activation of MEK1/2 & PI3K pathways involving an upstream kinase, TrkA. Bioactive small molecules with neurotrophic and neuritogenic actions, like vorinostat identified in the present study, hold great promise as therapeutic agents for treatment of neurodegenerative diseases and neuronal injuries by virtue of their ability to stimulate neuritic outgrowth. [Read the Full Post]

Targeting synthetic lethality between the SRC kinase and the EPHB6 receptor may benefit cancer treatment

593 | Apr 22 2018

Paul JM et al. indicated the observations are of potential practical importance, since TNBC is an aggressive heterogeneous malignancy with a very high rate of patient mortality due to the lack of targeted therapies, and our work indicates that FDA-approved SRC inhibitors may potentially be used in a personalized manner for treating patients with EPHB6-deficient TNBC. Our findings are also of a general interest, as EPHB6 is downregulated in multiple malignancies and our data serve as a proof of principle that EPHB6 deficiency may be targeted by small molecule inhibitors in the SL approach. [Read the Full Post]

Abl2 kinase phosphorylates Bi-organellar regulator MNRR1 in mitochondria, stimulating respiration

756 | Apr 19 2018

Aras S et al. showed that binding of MNRR1 to COX is promoted by phosphorylation at tyrosine-99 and that this interaction stimulates respiration. We show that phosphorylation of MNRR1 takes place in mitochondria and is mediated by Abl2 kinase (ARG). A family with Charcot-Marie-Tooth disease type 1A with an exaggerated phenotype harbors a Q112H mutation in MNRR1, located in a domain that is necessary for transcriptional activation by MNRR1. Furthermore, the mutation causes the protein to function suboptimally in the mitochondria in response to cellular stress. The Q112H mutation hinders the ability of the protein to interact with Abl kinase, leading to defective tyrosine phosphorylation and a resultant defect in respiration. [Read the Full Post]

Crystal Structure of the FGFR4/LY2874455 Complex Reveals Insights into the Pan-FGFR Selectivity of LY2874455

821 | Apr 16 2018

Wu D et al. revealed that the interactions of LY2874455 to FGFR4 are largely conserved in 4 FGFRs, explaining at least partly, the broad inhibitory activity of LY2874455 toward 4 FGFRs. Consequently, our studies reveal new insights into the pan-FGFR selectivity of LY2874455 and provide a structural basis for developing novel FGFR inhibitors that target FGFR1-4 broadly. [Read the Full Post]

Proliferation Markers Are Associated with MET Expression in Hepatocellular Carcinoma and Predict Tivantinib Sensitivity In Vitro

0 | Apr 15 2018

Rebouissou S et al. indicated that tivantinib acts as an antimitotic compound, and cell proliferation markers are the best predictors of its antitumor efficacy in cell lines. Ki67 expression should be tested in clinical trials to predict tivantinib response. [Read the Full Post]

The HER2 inhibitor TAK165 Sensitizes Human Acute Myeloid Leukemia Cells to Retinoic Acid-Induced Myeloid Differentiation by activating MEK/ERK mediated RARα/STAT1 axis

1100 | Apr 11 2018

Shao X et al. indicated that our study is the first to evaluate the synergy of TAK165 and ATRA in AML cell differentiation and to assess new opportunities for the combination of TAK165 and ATRA as a promising approach for future differentiation therapy. [Read the Full Post]

Anaplastic lymphoma kinase regulates binge-like drinking and dopamine receptor sensitivity in the ventral tegmental area

656 | Apr 10 2018

Dutton JW 3rd et al. supported the possibility that ALK might be a novel target of pharmacotherapy for reducing excessive alcohol consumption. [Read the Full Post]

In situ electrochemical evaluation of dsDNA interaction with the anticancer drug danusertib nitrenium radical product using the DNA-electrochemical biosensor

1947 | Apr 05 2018

Diculescu VC et al. indicated the danusertib nitrenium cation radical redox metabolite was covalently attached to the C8 of guanine residues preventing their oxidation. An interaction mechanism of dsDNA-danusertib is proposed and the formation of the danusertib redox nitrenium radical metabolite-guanine adduct explained. [Read the Full Post]

HER Family Receptors are Important Theranostic Biomarkers for Cervical Cancer: Blocking Glucose Metabolism Enhances the Therapeutic Effect of HER Inhibitors

714 | Apr 02 2018

Martinho O et al. proposed that the use of HER inhibitors in association with glycolysis blockers can be a potentially effective treatment option for HER-positive cervical cancer patients. [Read the Full Post]

Establishment and antitumor effects of dasatinib and PKI-587 in BD-138T, a patient-derived muscle invasive bladder cancer preclinical platform with concomitant EGFR amplification and PTEN deletion

433 | Apr 01 2018

Chang N et al. demonstrated that dasatinib and PKI-587 might serve as promising anticancer drug candidates for treating MIBC with combined EGFR gene amplification and PTEN deletion. [Read the Full Post]

The Novel PIM1 Inhibitor NMS-P645 Reverses PIM1-Dependent Effects on TMPRSS2/ERG Positive Prostate Cancer Cells And Shows Anti-Proliferative Activity in Combination with PI3K Inhibition

891 | Mar 31 2018

Mologni L et al. supported the use of combination strategies with PIM and PI3K inhibitors as effective treatment for PCa cases. [Read the Full Post]

FYN promotes breast cancer progression through epithelial-mesenchymal transition

1254 | Mar 29 2018

Xie YG et al. found that FYN was overexpressed in breast cancer and overexpression of FYN promoted cell proliferation, migration and invasion in the MCF10A cells, whereas depletion of FYN suppressed cell proliferation, migration and invasion in the MDA-MB-231 cells. Moreover, FYN upregulated the expression of mesenchymal markers and epithelial-mesenchymal transition (EMT)-related transcription factors, and downregulated the expression of epithelial markers, suggesting that FYN induces EMT in breast cancer cells. Furthermore, FYN was transcriptionally regulated by FOXO1 and mediated FGF2-induced EMT through both the PI3K/AKT and ERK/MAPK pathways. [Read the Full Post]

A Cross-Species Study of PI3K Protein-Protein Interactions Reveals the Direct Interaction of P85 and SHP2

494 | Mar 26 2018

Breitkopf SB et al. indicated a disruption of the SHP2-p85 complex took place after insulin/IGF1 stimulation or imatinib treatment, suggesting that the direct SHP2-p85 interaction was both independent of AKT activation and positively regulates the ERK signaling pathway. [Read the Full Post]

Co-Targeting IGF-1R and Autophagy Enhances the Effects of Cell Growth Suppression and Apoptosis Induced by the IGF-1R Inhibitor NVP-AEW541 in Triple-Negative Breast Cancer Cells

409 | Mar 25 2018

Wu W et al. revealed that combined use autophagy-disrupting agents can enhance the therapeutic efficacy of IGF-1R inhibitors in TNBC cells and may provide a valuable treatment strategy for IGF-1R inhibitor-based therapies for TNBC and other IGF-1 signaling-associated tumors. [Read the Full Post]

Co-inhibition of EGFR and IGF1R synergistically impacts therapeutically on adrenocortical carcinoma

405 | Mar 25 2018

Xu L et al. showed a significant over-expression of EGFR (66.67%) and IGF1R (80.0%) in ACC. Besides, the co-overexpression of EGFR and IGF1R was seen in 8/15 ACCs, as compared with ACAs (P<0.05). Erlotinib and NVP-AEW541 significantly inhibited cell viability and induced apoptosis by blocking phosphorylation of MEK/ERK and AKT, respectively. Meanwhile, we found that single inhibition of IGF1R induced compensatory activation of MEK/ERK, leading to sustained activation of mTOR, which represent as aggregation of EGFR and IGF1R downstream components. More importantly, the combination of Erlotinib and NVP-AEW541 enhances anti-tumour efficacy compared to treatment with either agent alone or to untreated control in vitro and vivo. [Read the Full Post]

Nordihydroguaiaretic acid impairs prostate cancer cell migration and tumor metastasis by suppressing neuropilin 1

432 | Mar 03 2018

Li X et al. revealed a novel mechanism underlying the anti-metastasis function of NDGA and indicate the potential value of NDGA in NRP1 targeting therapy for selected subtypes of cancer. [Read the Full Post]

Ginsenoside Rg3 inhibits epithelial-mesenchymal transition (EMT) and invasion of lung cancer by down-regulating FUT4

841 | Feb 17 2018

Tian L et al. indicated Rg3 inhibits EMT and invasion of lung cancer by down-regulating FUT4 mediated EGFR inactivation and blocking MAPK and NF-κB signal pathways. Rg3 may be a potentially effective agent for the treatment of lung cancer. [Read the Full Post]

FOXM1 confers resistance to gefitinib in lung adenocarcinoma via a MET/AKT-dependent positive feedback loop

446 | Feb 16 2018

Wang Y et al. indicate that FOXM1 promotes acquired resistance to gefitinib of lung adenocarcinoma cells, and FOXM1 crosstalks with MET/AKT signaling to form a positive feedback loop to promote lung adenocarcinoma development. [Read the Full Post]

Dihydroartemisin inhibits glioma invasiveness via a ROS to P53 to β-catenin signaling

2242 | Feb 16 2018

Que Z et al. indicated that DHA inhibited the migration and invasion of human glioma cells with different types of p53 via different pathways. [Read the Full Post]

Proliferation Markers Are Associated with MET Expression in Hepatocellular Carcinoma and Predict Tivantinib Sensitivity In Vitro

446 | Feb 15 2018

Rebouissou S et al. showed that Tivantinib acts as an antimitotic compound, and cell proliferation markers are the best predictors of its antitumor efficacy in cell lines. Ki67 expression should be tested in clinical trials to predict tivantinib response. [Read the Full Post]

Development of Novel Patient-Derived Preclinical Models from Malignant Effusions in Patients with Tyrosine Kinase Inhibitor-Resistant Clear Cell Renal Cell Carcinoma

1020 | Feb 02 2018

Jang J et al. suggested that the PDC-PDX preclinical model we developed using malignant effusions can be a useful preclinical model to interrogate sensitivity to targeted agents based on genomic alterations. [Read the Full Post]

3D microtumors in vitro supported by perfused vascular networks

1221 | Feb 02 2018

Sobrino A et al. indicated that tumors in the VMT show strong metabolic heterogeneity when imaged using NADH Fluorescent Lifetime Imaging Microscopy and, compared to their surrounding stroma, many show a higher free/bound NADH ratio consistent with their known preference for aerobic glycolysis. The VMT platform provides a unique model for studying vascularized solid tumors in vitro. [Read the Full Post]

BEZ235 (PIK3/mTOR inhibitor) Overcomes Pazopanib Resistance in Patient-Derived Refractory Soft Tissue Sarcoma Cells

0 | Feb 01 2018

Kim HK et al. considered as treatment option in STS patient who have failed to pazopanib in the context of clinical trials. [Read the Full Post]

Inhibition of spleen tyrosine kinase activation ameliorates inflammation, cell death, and steatosis in alcoholic liver disease

1182 | Jan 24 2018

Bukong TN et al. demonstrated a novel, functional, and multicellular role for SYK phosphorylation in modulating immune cell-driven liver inflammation, hepatocyte cell death, and steatosis at different stages of ALD. [Read the Full Post]

Arsenic trioxide and all-trans-retinoic acid selectively exert synergistic cytotoxicity against FLT3-ITD AML cells via co-inhibition of FLT3 signaling pathways

860 | Jan 13 2018

Wang LN et al. provided experimental evidence that supports further exploration of ATO/ATRA in FLT3-ITD AML in vivo and warrants a clinical evaluation of regimens comprising an ATO/ATRA combination. [Read the Full Post]

Epigallocatechin gallate reverses cTnI-low expression-induced age-related heart diastolic dysfunction through histone acetylation modification

1581 | Jan 11 2018

Pan B et al. provided new insights into histone acetylation mechanisms of EGCG treatment that may contribute to the prevention of CDD in ageing populations. [Read the Full Post]

No preclinical rationale for IGF1R directed therapy in chondrosarcoma of bone

696 | Jan 06 2018

Peterse EF et al. indicated that the IGF pathway is not essential for chondrosarcoma growth, migration or chemoresistance. [Read the Full Post]

Sunitinib Treatment Enhances Metastasis of Innately Drug-Resistant Breast Tumors

0 | Jan 02 2018

Wragg JW et al. unravel specific features of antiangiogenic resistance, with potential therapeutic implications. [Read the Full Post]

Adaptive and Acquired Resistance to EGFR Inhibitors Converge on the MAPK Pathway

958 | Jan 01 2018

Ma P et al. demonstrated that adaptive and acquired resistance to EGFR inhibitors can converge on the same pathway and credential cotargeting EGFR and MAPK as a promising therapeutic approach in EGFR mutant tumors. [Read the Full Post]

Ethacrynic acid improves the antitumor effects of irreversible epidermal growth factor receptor tyrosine kinase inhibitors in breast cancer

0 | Dec 24 2017

Liu B et al. concluded that EA synergistically enhances the antitumor effects of irreversible EGFR TKIs in breast cancer. [Read the Full Post]

Neratinib induces ErbB2 ubiquitylation and endocytic degradation via HSP90 dissociation in breast cancer cells

1241 | Dec 24 2017

Zhang Y et al. provided novel insights into the mechanism of ErbB2 inhibition by neratinib. [Read the Full Post]

Dasatinib inhibits actin fiber reorganization and promotes endothelial cell permeability through RhoA-ROCK pathway

1731 | Dec 21 2017

Dasgupta SK et al. suggested that ROCK inhibitors could serve as therapeutic modalities to ameliorate the dasatinib-induced pulmonary changes. [Read the Full Post]

Induction of Neuroendocrine Differentiation in Prostate Cancer Cells by Dovitinib (TKI-258) and its Therapeutic Implications

1583 | Dec 16 2017

Yadav SS et al. observed that both androgen receptor (AR) positive and AR-negative PCa cells differentiate into a NE phenotype upon treatment with Dovitinib. [Read the Full Post]

The AXL receptor tyrosine kinase is associated with adverse prognosis and distant metastasis in esophageal squamous cell carcinoma

1336 | Dec 15 2017

Hsieh MS et al. concluded that AXL is a strong adverse prognostic factor for ESCC. Therapeutic agents targeting AXL have great potential to improve prognosis of ESCC patients. [Read the Full Post]

Dual targeting of p53 and c-MYC selectively eliminates leukaemic stem cells

3277 | Dec 10 2017

Abraham SA et al. found that LSCs can be eradicated. [Read the Full Post]

MET Copy Number Gain Is Associated with Gefitinib Resistance in Leptomeningeal Carcinomatosis of EGFR-mutant Lung Cancer

1491 | Dec 10 2017

Nanjo S et al. suggested that combination therapy with MET inhibitors may be promising for controlling leptomeningeal carcinomatosis that acquires resistance to EGFR-TKIs [Read the Full Post]

EMT is associated with, but does not drive resistance to ALK inhibitors among EML4-ALK non-small cell lung cancer

0 | Dec 06 2017

Gower A et al. showed that EMT does not drive resistance to ALK inhibitors and HSP90 inhibition demonstrates more efficacy when further ALK inhibition may not. This study warrants more exploration of HSP90 inhibitors for ALK-positive patients who progress on 1st and 2nd line ALK inhibitor therapy. [Read the Full Post]

An Oncogenic ALK Fusion and an RRAS Mutation in KRAS Mutation-Negative Pancreatic Ductal Adenocarcinoma

996 | Dec 06 2017

Shimada Y et al. showed that rare oncogenic aberrations, such as the ALK fusion and RRAS mutation, may drive pancreatic carcinogenesis independent of the KRAS mutation. [Read the Full Post]

Gremlin inhibits UV-induced skin cell damages via activating VEGFR2-Nrf2 signaling

705 | Dec 05 2017

Ji C et al. concluded that gremlin protects skin cells from UV damages via activating VEGFR2-Nrf2 signaling. Gremlin could be further tested as a novel anti-UV skin protectant. [Read the Full Post]

Arsenite suppresses angiogenesis of vascular endothelial cells mediated by Platelet Derived Growth Factor Receptor-beta

837 | Dec 03 2017

Wang X et al. concluded that arsenite suppressed the angiogenesis of the vascular endothelial cells, that this effect is mediated by PDGFR-beta, and postulate that it might contribute to the injuries of blood vessel in arsenism. [Read the Full Post]

Complex Roles of Annexin A2 in Host Blood-Brain Barrier Invasion by Cryptococcus neoformans

797 | Nov 27 2017

Fang W et al. indicated that AnxA2 played complex roles in traversal of C. neoformans across host BMECs, which might be dependent on downstream cofilin to inhibit fungal adhesion but rely on its partner S100A10 to promote cryptococcal transcytosis. [Read the Full Post]

Amplification of EGFR Wild-Type Alleles in Non-Small Cell Lung Cancer Cells Confers Acquired Resistance to Mutation-Selective EGFR Tyrosine Kinase Inhibitors

0 | Nov 21 2017

Nukaga S et al. provided evidence of wild-type allele-mediated resistance, a novel concept of acquired resistance in response to mutation-selective inhibitor therapy in cancer treatment. [Read the Full Post]

The platelet-derived growth factor receptor/STAT3 signaling pathway regulates the phenotypic transition of corpus cavernosum smooth muscle in rats

767 | Nov 09 2017

Yan JF et al. indicated that through activation of the PDGFR/STAT3 signaling pathway, PDGF promoted the synthetic phenotype transition; thus, regulation of this pathway might contribute to ED therapy. [Read the Full Post]

Spleen Tyrosine Kinase Mediates EGFR Signaling to Regulate Keratinocyte Terminal Differentiation

965 | Nov 09 2017

Wu NL et al. unraveled the role of Syk in EGFR-mediated signaling and reveals regulatory roles of Syk in keratinocyte differentiation, suggesting the clinical potential of topical or systemic Syk inhibitors in the treatment of skin diseases with aberrant differentiation. [Read the Full Post]

Quantitative proteomics of breast tumors: Tissue quality assessment to clinical biomarkers

1395 | Nov 06 2017

Chen Y, et al. showed that combined with biomarkers for tissue quality and histological content are implemented in a three-tier multiplexed assay platform, which is translated from cell line models into frozen tumor tissues banked from breast cancer patients. [Read the Full Post]

Platelet-derived growth factor BB enhances osteoclast formation and osteoclast precursor cell chemotaxis

1222 | Nov 05 2017

Li DQ et al. showed that PDGF-BB enhanced RAW264.7 cell migration and gene expression of osteoclastogenic signaling molecules (i.e., nuclear factor of activated T cells 1, dendrocyte-expressed seven transmembrane protein, and B-cell lymphoma 2), and treatment with AG-1295, AG-490, or S3I-201 (a STAT3 inhibitor) reduced this effect. PDGF-BB enhanced osteoclast formation, osteoclast precursor cell chemotaxis, and phosphorylation of STAT3, Akt, and ERK1/2. but AG-1295 and AG-490 reduced this effect. These findings reflect the complexity of PDGF-BB in bone biology. [Read the Full Post]

Regulated intramembrane proteolysis of the AXL receptor kinase generates an intracellular domain that localizes in the nucleus of cancer cells

728 | Nov 04 2017

Lu Y et al. suggested that AXL can undergo sequential processing mediated by various proteases kept in a homeostatic balance. [Read the Full Post]

IGF-II-mediated downregulation of peroxisome proliferator-activated receptor-γ coactivator-1α in myoblast cells involves PI3K/Akt/FoxO1 signaling pathway

539 | Nov 03 2017

Mu X et al. indicated that IGF-II reduces PGC-1α expression in skeletal muscle cells through a mechanism involving PI3K-Akt-FoxO1 but not p38 MAPK or Erk1/2 MAPK pathways. [Read the Full Post]

Antitumor effect of FGFR inhibitors on a novel cholangiocarcinoma patient derived xenograft mouse model endogenously expressing an FGFR2-CCDC6 fusion protein

0 | Nov 01 2017

Wang Y et al. provided a strong rationale for the investigation of FGFR inhibitors, particularly BGJ398, as a therapeutic option for cholangiocarcinoma patients harboring FGFR2 fusions. [Read the Full Post]

S100B impairs glycolysis via enhanced poly(ADP-ribosyl)ation of glyceraldehyde-3-phosphate dehydrogenase in rodent muscle cells

1090 | Oct 30 2017

Hosokawa K et al. concluded that S100B as a humoral factor may impair glycolysis in muscle cells independent of insulin action, and the effect may be attributed to the inhibition of GAPDH activity from enhanced poly(ADP-ribosyl)ation of the enzyme. conclude that S100B as a humoral factor may impair glycolysis in muscle cells independent of insulin action, and the effect may be attributed to the inhibition of GAPDH activity from enhanced poly(ADP-ribosyl)ation of the enzyme. [Read the Full Post]

EMT is associated with, but does not drive resistance to ALK inhibitors among EML4-ALK non-small cell lung cancer

0 | Oct 25 2017

Gower A et al. showed that EMT does not drive resistance to ALK inhibitors and HSP90 inhibition demonstrates more efficacy when further ALK inhibition may not. This study warrants more exploration of HSP90 inhibitors for ALK-positive patients who progress on 1st and 2nd line ALK inhibitor therapy. [Read the Full Post]

Novel Mechanisms for the Antifibrotic Action of Nintedanib

1270 | Oct 22 2017

Rangarajan S et al. showed that Nintedanib down-regulated protein and mRNA expression of extracellular matrix (ECM) proteins, fibronectin, and collagen 1a1 while inhibiting transforming growth factor (TGF)-β1-induced myofibroblast differentiation. Nintedanib also induced beclin-1-dependent, ATG7-independent autophagy. Nintedanib's ECM-suppressive actions were not mediated by canonical autophagy. Nintedanib inhibited early events in TGF-β signaling, specifically tyrosine phosphorylation of the type II TGF-β receptor, activation of SMAD3, and p38 mitogen-activated protein kinase. Nintedanib down-regulates ECM production and induces noncanonical autophagy in IPF fibroblasts while inhibiting TGF-β signaling. [Read the Full Post]

Crosstalk between the IGF-1R/AKT/mTORC1 pathway and the tumor suppressors p53 and p27 determines cisplatin sensitivity and limits the effectiveness of an IGF-1R pathway inhibitor

486 | Oct 19 2017

Davaadelger B, et al. demonstrated 1) p53 expression determines the effect of IGF-1R inhibition on cancer cell CP response, and 2) crosstalk between the IGF-1R/AKT/mTORC1 pathway and p53 and p27 can reduce cancer cell responsiveness to chemotherapy and may ultimately limit the effectiveness of IGF-1R pathway inhibitors in the clinic. [Read the Full Post]

Resistance Mechanism against Trastuzumab in HER2-Positive Cancer Cells and Its Negation by Src Inhibition

1026 | Oct 16 2017

Jin MH et al. suggested that Src inhibition may be an effective measure to overcome trastuzumab resistance in HER2-positive cancer. [Read the Full Post]

Isocitrate Dehydrogenase Mutations Confer Dasatinib Hypersensitivity and SRC Dependence in Intrahepatic Cholangiocarcinoma

0 | Oct 12 2017

Saha SK et al. provided a systematic and broadly applicable approach to define targets of kinase inhibitors underlying drug responsiveness. [Read the Full Post]

Diverse, Biologically Relevant, and Targetable Gene Rearrangements in Triple-Negative Breast Cancer and Other Malignancies

1140 | Oct 08 2017

Shaver TM et al. identified a diverse array of novel and known hybrid transcripts, including rearrangements between noncoding regions and clinically relevant genes such as ALK, CSF1R, and CD274/PD-L1 The over 1,000 genetic alterations we identified highlight the importance of considering noncoding gene rearrangement partners, and the targetable gene fusions identified in TNBC demonstrate the need to advance gene fusion detection for molecularly heterogeneous cancers. [Read the Full Post]

Cabozantinib is selectively cytotoxic in acute myeloid leukemia cells with FLT3-internal tandem duplication (FLT3-ITD)

1034 | Oct 03 2017

Lu JW et al. showed that Clinical trials evaluating the efficacy of cabozantinib in acute myeloid leukemia (AML) with FLT3-ITD are warranted. [Read the Full Post]

In Vivo Visualization and Characterization of Epithelial-Mesenchymal Transition in Breast Tumors

935 | Oct 03 2017

Zhao Z et al. provided a novel opportunity for visualizing tumor EMT at the single-cell level and may help to reveal the intricacies underlying tumor dynamics and treatment responses. [Read the Full Post]

An FGFR inhibitor converts the tumor promoting effect of TGF-β by the induction of fibroblast-associated genes of hepatoma cells

0 | Oct 02 2017

Zhang HR et al. indicated that FGFR inhibitor treatment converts the effect of TGF-β on the hepatocellular carcinoma cells from tumor promotion into tumor inhibition by enhancing the induction effect of TGF-β on some fibroblast-associated genes. Converting human liver cancer cells into less malignant fibroblast-like cells and inducing tumor parenchyma cell fibrosis provides an alternative strategy for limiting tumor progression. [Read the Full Post]

Heterogeneity of macrophage infiltration and therapeutic response in lung carcinoma revealed by 3D organ imaging

850 | Sep 30 2017

Cuccarese MF et al. revealed that TAM density was heterogeneous across tumours in the same animal, overall TAM density is different among separate pulmonary tumour models, nanotherapeutic drug delivery correlated with TAM heterogeneity, and successful response to CSF-1R blockade is characterized by enhanced TAM penetration throughout and within tumours. [Read the Full Post]

Basic FGF and PDGF-BB synergistically stimulate hyaluronan and IL-6 production by orbital fibroblasts

0 | Sep 27 2017

Virakul S et al. found that multi-target therapy directed at the bFGF and PDGF pathways may potentially be of interest for the treatment of GO. [Read the Full Post]

Neurotoxic reactive astrocytes are induced by activated microglia

877 | Sep 26 2017

Liddelow SA et al. help to explain why CNS neurons die after axotomy, strongly suggest that A1 astrocytes contribute to the death of neurons and oligodendrocytes in neurodegenerative disorders, and provide opportunities for the development of new treatments for these diseases. [Read the Full Post]

Involvement of PARK2-Mediated Mitophagy in Idiopathic Pulmonary Fibrosis Pathogenesis

0 | Sep 14 2017

Kobayashi K et al. suggested that insufficient mitophagy-mediated PDGFR/PI3K/AKT activation, which is mainly attributed to reduced PARK2 expression, is a potent underlying mechanism for myofibroblast differentiation and proliferation in fibroblastic foci formation during IPF pathogenesis. [Read the Full Post]

IGF/STAT3/NANOG/Slug Signaling Axis Simultaneously Controls Epithelial-Mesenchymal Transition and Stemness Maintenance in Colorectal Cancer

730 | Sep 01 2017

Yao C et al. defined the crucial functions of IGF/STAT3/NANOG/Slug signaling axis in the progression of CRC by operating EMT and CSCs properties, which make them served as potential therapeutic targets for treatment of CRC. [Read the Full Post]

Anticancer effects of the engineered stem cells transduced with therapeutic genes via a selective tumor tropism caused by vascular endothelial growth factor toward HeLa cervical cancer cells

999 | Aug 31 2017

Kim HS et al. showed that GESTECs transduced with CD gene and IFN-β may provide a potential of a novel gene therapy for anticervical cancer treatments via their selective tumor tropism derived from VEGF and VEGFR2 expressions between HeLa cells and the GESTECs. [Read the Full Post]

Oncogene swap as a novel mechanism of acquired resistance to epidermal growth factor receptor-tyrosine kinase inhibitor in lung cancer

1353 | Aug 31 2017

Mizuuchi H et al. analyzed multiple lesions from a patient who died of acquired resistance to gefitinib, then found a clinical example of an oncogene swap in which the EGFR mutation was lost and a MET gene copy was gained. In conclusion, an "oncogene swap" from EGFR to MET is a novel resistant mechanism to the EGFR-TKI. This novel mechanism should be considered in order to avoid futile inhibition of the original oncogene. [Read the Full Post]

Fisetin, a dietary phytochemical, overcomes Erlotinib-resistance of lung adenocarcinoma cells through inhibition of MAPK and AKT pathways

759 | Aug 21 2017

Zhang L et al. showed that Fisetin effectively increased sensitivity of Erlotinib-resistant lung cancer cells to Erlotinib, possibly by inhibiting aberrant activation of MAPK and AKT signaling pathways resulted from AXL suppression. [Read the Full Post]

An FGFR inhibitor converts the tumor promoting effect of TGF-β by the induction of fibroblast-associated genes of hepatoma cells

2257 | Aug 16 2017

Zhang HR et al. indicated that FGFR inhibitor treatment converts the effect of TGF-β on the hepatocellular carcinoma cells from tumor promotion into tumor inhibition by enhancing the induction effect of TGF-β on some fibroblast-associated genes. Converting human liver cancer cells into less malignant fibroblast-like cells and inducing tumor parenchyma cell fibrosis provides an alternative strategy for limiting tumor progression. [Read the Full Post]

Akt Activation Mediates Acquired Resistance to Fibroblast Growth Factor Receptor Inhibitor BGJ398

1116 | Aug 15 2017

Datta J et al. suggested a role for Akt pathway in mediating acquired resistance to FGFR inhibition. [Read the Full Post]

Preclinical evaluation of potential therapeutic targets in dedifferentiated liposarcoma

957 | Aug 13 2017

Hanes R et al. indicated that FGFR inhibitors have therapeutic potential in the treatment of DDLPS with amplified FRS2. [Read the Full Post]

ZFX Facilitates Cell Proliferation and Imatinib Resistance in Chronic Myeloid Leukemia Cells

1050 | Aug 10 2017

Jingjing Wu et al. suggested that ZFX is a novel oncogene promoting cell proliferation and inducing imatinib resistance via PI3K/Akt signaling pathway. ZFX may represent a potential therapeutic target in CML. [Read the Full Post]

Substitution scanning identifies a novel, catalytically active ibrutinib-resistant BTK cysteine 481 to threonine (C481T) variant

0 | Aug 04 2017

Hamasy A et al. identified three potential ibrutinib resistance scenarios for cysteine 481 replacement. [Read the Full Post]

Image-Guided Radiotherapy Targets Macromolecules through Altering the Tumor Microenvironment

2152 | Aug 01 2017

Appelbe OK et al. suggest repurposing image-guided radiotherapy as a tool to guide cancer nanomedicine delivery, enhancing local control for primary tumors and metastatic disease while limiting systemic toxicity. [Read the Full Post]

Y-632 inhibits heat shock protein 90 (Hsp90) function by disrupting the interaction between Hsp90 and Hsp70/Hsp90 organizing protein, and exerts antitumor activity in vitro and in vivo

2137 | Aug 01 2017

Wang W et al. believe that Y-632, acting as a novel small-molecule inhibitor of the Hsp90-Hsp70/Hsp90 organizing protein complex, has great potential to be a promising Hsp90 inhibitor for cancer therapy, such as for imatinib-resistant leukemia. [Read the Full Post]

Sunitinib Treatment Enhances Metastasis of Innately Drug-Resistant Breast Tumors

1863 | Jul 31 2017

Wragg JW et al. unraveled specific features of antiangiogenic resistance, with potential therapeutic implications. [Read the Full Post]

Long-term treatment with EGFR inhibitor erlotinib attenuates renal inflammatory cytokines but not nephropathy in Alport syndrome mouse model

1637 | Jul 28 2017

Omachi K et al. suggested that EGFR signaling is upregulated in kidney, but although inhibiting this signaling pathway suppressed renal inflammatory cytokines, it did not ameliorate renal dysfunction in AS mouse model. [Read the Full Post]

miR-17-5p down-regulation contributes to erlotinib resistance in non-small cell lung cancer cells

1581 | Jul 28 2017

Zhang W et al. indicated that miR-17-5p down-regulation contributes to erlotinib resistance of NSCLC by modulating its target genes such as EZH1 and plasma miR-17-5p might be a potential biomarker of erlotinib response in NSCLC patients. [Read the Full Post]

PI3 Kinase Pathway and MET Inhibition is Efficacious in Malignant Pleural Mesothelioma

1323 | Jul 27 2017

Kanteti R et al. showed that a combination of crizotinib with BKM120 was highly synergetic in inhibiting MPM tumor growth. In conclusion our findings suggest that dual inhibition of PI3K and MET pathway is an effective strategy in treating MPM as compared to a single agent. [Read the Full Post]

Green tea polyphenol EGCG suppresses osteosarcoma cell growth through upregulating miR-1

1399 | Jul 27 2017

Zhu K et al. suggested that EGCG has an anticancer effect on OS cells, at least partially, through regulating miR-1/c-MET interaction. [Read the Full Post]

17β-estradiol-induced growth of triple-negative breast cancer cells is prevented by the reduction of GPER expression after treatment with gefitinib

3366 | Jul 26 2017

Girgert R et al. showed that reduction of GPER expression is a promising therapeutic approach for TNBC. [Read the Full Post]

cMET inhibitor crizotinib impairs angiogenesis and reduces tumor burden in the C3(1)-Tag model of basal-like breast cancer

1432 | Jul 26 2017

Cozzo AJ et al. showed cMET inhibition by crizotinib limited tumor development and microvascular density in basal-like tumor-bearing mice but did not appear to be an effective preventive agent for BBC. [Read the Full Post]

Metalloproteinase-9 contributes to endothelial dysfunction in atherosclerosis via protease activated receptor-1

823 | Jul 13 2017

Florence JM et al. demonstrated that metalloproteinase-9 could activate endothelial cells and induce their apoptosis via cleavage of protease activated receptor-1. In summary, better understanding of metalloproteinase-9's pathogenic capabilities as well as novel signaling pathways involved may lead to development of treatments which may provide additional benefits to atherosclerosis patients with a history of second hand smoke exposure. [Read the Full Post]

MET Inhibition in Clear Cell Renal Cell Carcinoma

0 | Jul 01 2017

Xie Z et al. provided further preclinical rationale for dual MET/VEGFR2 inhibition in ccRCC. [Read the Full Post]

miR-17-5p down-regulation contributes to erlotinib resistance in non-small cell lung cancer cells

1973 | Jun 29 2017

Zhang W et al. indicated that miR-17-5p down-regulation contributes to erlotinib resistance of NSCLC by modulating its target genes such as EZH1 and plasma miR-17-5p might be a potential biomarker of erlotinib response in NSCLC patients [Read the Full Post]

Amplification of EGFR Wild-Type Alleles in Non-Small Cell Lung Cancer Cells Confers Acquired Resistance to Mutation-Selective EGFR Tyrosine Kinase Inhibitors

2349 | Jun 27 2017

Nukaga S et al. provided evidence of wild-type allele-mediated resistance, a novel concept of acquired resistance in response to mutation-selective inhibitor therapy in cancer treatment. [Read the Full Post]

Exploiting Temporal Collateral Sensitivity in Tumor Clonal Evolution.

1186 | Jun 17 2017

Zhao B, et al. identified new strategies to treat dynamic tumor vulnerabilities. [Read the Full Post]

Ethacrynic acid improves the antitumor effects of irreversible epidermal growth factor receptor tyrosine kinase inhibitors in breast cancer

2232 | Jun 16 2017

Liu B et al. concluded that EA synergistically enhances the antitumor effects of irreversible EGFR TKIs in breast cancer. [Read the Full Post]

Functionalized gold nanoparticles improve afatinib delivery into cancer cells

2020 | Jun 16 2017

Coelho SC et al. found that PEGAuNPs with afatinib is a promising antitumor delivery system for cancer therapy as it improves drug efficacy, allowing a reduction in drug dose used and minimizing possible toxicity-related side effects. [Read the Full Post]

Platelet-derived growth factor (PDGF)-induced activation of Erk5 MAP-kinase is dependent on Mekk2, Mek1/2, PKC and PI3-kinase, and affects BMP signaling

4709 | Jun 14 2017

Tsioumpekou M et al. found that PDGF-BB-induced Erk5 activation involves parallel stimulatory and inhibitory pathways and promotes Smad1/5/8 signaling. [Read the Full Post]

Metformin and gefitinib cooperate to inhibit bladder cancer growth via both AMPK and EGFR pathways joining at Akt and Erk

1461 | Jun 11 2017

Peng M, et al. found these two drugs may be an excellent combination for the treatment of bladder cancer through intravesical instillation. [Read the Full Post]

The new and recurrent FLT3 juxtamembrane deletion mutation shows a dominant negative effect on the wild-type FLT3 receptor

1299 | May 31 2017

Sandhöfer N et al. that FLT3 p.Q569Vfs*2 is the first FLT3 mutation with a dominant negative effect on the WT receptor. [Read the Full Post]

Synergistic effect of pacritinib with erlotinib on JAK2-mediated resistance in epidermal gowth factor receptor mutation-positive non-small cell lung Cancer

0 | May 28 2017

Ochi N et al. found that pacritinib combined with EGFR-TKI might be a potent strategy against JAK2-mediated EGFR-TKI resistance. [Read the Full Post]

Epidermal growth factor receptor inhibitor cancer drug gefitinib modulates cell growth and differentiation of acute myeloid leukemia cells via histamine receptors

1313 | May 28 2017

Yadav M et al. found that HRs play critical roles in anti-cancer effects of gefitinib in both EGFR-deficient and EGFR-rich environments. [Read the Full Post]

FGFR3-TACC3 fusion proteins act as naturally occurring drivers of tumor resistance by functionally substituting for EGFR/ERK signaling

1345 | May 21 2017

Daly C, et al. found that FGFR3-TACC3 fusion proteins may represent a novel mechanism of acquired resistance in EGFR-dependent cancers of multiple cell lineages. [Read the Full Post]

ErbB2-dependent downregulation of a pro-apoptotic protein Perp is required for oncogenic transformation of breast epithelial cells.

0 | May 18 2017

Khan IA et al. have identified a novel mechanism of ErbB2-mediated mechanism of anoikis resistance of ErbB2-overproducing breast epithelial cells. [Read the Full Post]

Synthetic Lethal Targeting of ARID1A-Mutant Ovarian Clear Cell Tumors with Dasatinib

2910 | May 17 2017

Miller RE et al. suggested that dasatinib merits investigation for the treatment of patients with ARID1A-mutant OCCC. [Read the Full Post]

Constructing and Validating High-Performance MIEC-SVM Models in Virtual Screening for Kinases: A Better Way for Actives Discovery

0 | May 16 2017

Sun H et al. showed that the optimized MIEC-SVM model, which identified 7 actives with IC50 < 10 μM from 50 purchased compounds (namely hit rate of 14%, and 4 in nM level) and performed much better than Autodock (3 actives with IC50 < 10 μM from 50 purchased compounds, namely hit rate of 6%, and 2 in nM level), suggesting that the proposed strategy is a powerful tool in structure-based virtual screening [Read the Full Post]

Hiding inside? Intracellular expression of non-glycosylated c-kit protein in cardiac progenitor cells

2682 | May 15 2017

Shi H et al. demonstrated for the first time that c-kit is not only expressed in CDCs but may also directly participate in CDC differentiation into an endothelial lineage. [Read the Full Post]

EGFR Activation Leads to Cell Death Independent of PI3K/AKT/mTOR in an AD293 Cell Line

0 | May 14 2017

Treda C et al. showed another EGFR function, dependent on environmental factors, which could be employed in therapy and drug design. [Read the Full Post]

A Platform for Rapid, Quantitative Assessment of Multiple Drug Combinations Simultaneously in Solid Tumors In Vivo

1711 | May 12 2017

Dey J et al. found a platform for rapid, quantitative assessment of multiple drug combinations simultaneously in solid tumors In vivo. [Read the Full Post]

Src as a Therapeutic Target in Biliary Tract Cancer.

0 | May 11 2017

Nam AR et al. suggested that Src might be a potential therapeutic target in BTC. [Read the Full Post]

Utilising the EGFR interactome to identify mechanisms of drug resistance in non-small cell lung cancer - Proof of concept towards a systems pharmacology approach.

0 | May 09 2017

Saafan H et al.found that knowledge of these mechanisms is a pivotal step to build an integrative model of drug resistance in a systems pharmacology manner and to be able to investigate the interplay of these mechanisms and ultimately recommend combinatorial treatment strategies to overcome drug resistance. [Read the Full Post]

Utilising the EGFR interactome to identify mechanisms of drug resistance in non-small cell lung cancer - Proof of concept towards a systems pharmacology approach.

0 | May 08 2017

Saafan H et al. found that knowledge of these mechanisms is a pivotal step to build an integrative model of drug resistance in a systems pharmacology manner and to be able to investigate the interplay of these mechanisms and ultimately recommend combinatorial treatment strategies to overcome drug resistance. [Read the Full Post]

Neuritin Mediates Activity-Dependent Axonal Branch Formation in Part via FGF Signaling.

3056 | May 07 2017

Shimada T et al suggested that neuritin and FGF cooperate in inducing mossy fiber sprouting through FGF signaling. Together, these results suggest that FGF and neuritin-mediated axonal branch induction are involved in the aggravation of epilepsy. [Read the Full Post]

EGFR inhibitors identified as a potential treatment for chordoma in a focused compound screen

0 | May 07 2017

Scheipl S et al provided evidence for exploring the efficacy of EGFR inhibitors in the treatment of patients with chordoma and studying possible resistance mechanisms to these compounds in vitro and in vivo. [Read the Full Post]

The role of PDGF-B/TGF-β1/neprilysin network in regulating endothelial-to-mesenchymal transition in pulmonary artery remodeling

0 | May 06 2017

Song S et al. identified a novel mechanism to reveal the formation of EndoMT in PAH, and implied that imatinib may serve as a new therapeutic approach for treatment of the third cardiovascular disease. [Read the Full Post]

The role of PDGF-B/TGF-β1/neprilysin network in regulating endothelial-to-mesenchymal transition in pulmonary artery remodeling

1175 | Apr 29 2017

Song S et al. identified a novel mechanism to reveal the formation of EndoMT in PAH, and imply that imatinib may serve as a new therapeutic approach for treatment of the third cardiovascular disease. [Read the Full Post]

MAP3K19-Is-a-Novel-Regulator-of-TGF-B-Signaling-That-Impacts-Bleomycin-Induced-Lung-Injury-and-Pulmonary-Fibrosis

5077 | Apr 23 2017

Boehme SA et al suggested that inhibition of MAP3K19 may have a beneficial therapeutic effect in the treatment of IPF and represents a novel strategy to target this disease. [Read the Full Post]

Lassa virus cell entry via dystroglycan involves an unusual pathway of macropinocytosis.

0 | Apr 23 2017

Oppliger J et al revealed that DG can link LASV to an unusual pathway of macropinocytosis that causes only minimal perturbation of the host cell and identifies cellular kinases to be possible novel targets for therapeutic intervention. [Read the Full Post]

BAG3-mediated Mcl-1 stabilization contributes to drug resistance via interaction with USP9X in ovarian cancer

0 | Apr 20 2017

Habata S et al. suggested that inhibiting BAG3 in addition to anti-apoptotic Bcl-2 family proteins may be a useful therapeutic strategy for the treatment of chemoresistant ovarian cancers. [Read the Full Post]

EWS-FLI1-mediated suppression of the RAS-antagonist Sprouty 1 (SPRY1) confers aggressiveness to Ewing sarcoma

1314 | Apr 15 2017

Cidre-Aranaz F et al. suggested that targeting the FGFR/MAPK pathway can constitute a promising therapeutic approach for this devastating disease. [Read the Full Post]

Phosphatidylinositol 3-Kinase/Akt Mediates Integrin Signaling To Control RNA Polymerase I Transcriptional Activity

5999 | Apr 09 2017

Collectively, Wu C et al revealed, for the first time, a pivotal role of integrin signaling in regulation of RNA polymerase I transcriptional activity and shed light on the downstream signaling axis that participates in regulation of this key aspect of cell growth. [Read the Full Post]

Internal Tandem Duplication in FLT3 Attenuates Proliferation and Regulates Resistance to the FLT3 Inhibitor AC220 by Modulating p21Cdkn1a and Pbx1 in Hematopoietic Cells

1214 | Apr 07 2017

Abe M et al. found that FLT3-ITD is capable of inhibiting FLT3-ITD+ cell proliferation through the p21/Pbx1 axis and that treatments that antagonize FLT3-ITD contribute to the subsequent development of cells that are refractory to a FLT3-ITD inhibitor by disrupting p21 expression. [Read the Full Post]

Targeting FGFR2 with alofanib (RPT835) shows potent activity in tumour models

1449 | Apr 05 2017

Tsimafeyeu I et al showed that alofanib is a potent FGFR2 inhibitor and provide strong rationale for its evaluation in patients with FGFR2-driven cancers. [Read the Full Post]

Metabolic alterations and drug sensitivity of tyrosine kinase inhibitor resistant leukemia cells with a FLT3/ITD mutation

2371 | Apr 03 2017

Huang A et al revealed a metabolic signature of sorafenib-resistant cells and suggests that glycolytic inhibition may override such resistance and warrant further clinical investigation. [Read the Full Post]

iRGD-Decorated Polymeric Nanoparticles for the Efficient Delivery of Vandetanib to Hepatocellular Carcinoma: Preparation and in Vitro and in Vivo Evaluation

1165 | Apr 01 2017

Wang J et al. demonstrated that reformulating targeted therapeutic agents in NPs permits their systemic administration and thus significantly improves the potency of currently available, orally delivered agents. [Read the Full Post]

Overexpression of GAB2 in ovarian cancer cells promotes tumor growth and angiogenesis by upregulating chemokine expression

1371 | Mar 22 2017

Duckworth C et al suggestec that overexpression of GAB2 in ovarian cancer cells promotes tumor growth and angiogenesis by upregulating expression of CXCL1, CXCL2 and CXCL8 that is IKKβ-dependent. Co-targeting IKKβ and PI3K pathways downstream of GAB2 might be a promising therapeutic strategy for ovarian cancer that overexpresses GAB2. [Read the Full Post]

Tivantinib induces G2/M arrest and apoptosis by disrupting tubulin polymerization in hepatocellular carcinoma

0 | Mar 21 2017

Xiang Q et al suggested that the potent anti-tumor activity of tivantinib in HCC was achieved by targeting microtubule. Tivantinib treatment for patients with HCC should not be selected based on MET status. [Read the Full Post]

Treatment Efficacy and Resistance Mechanisms Using the Second-Generation ALK Inhibitor AP26113 in Human NPM-ALK–Positive Anaplastic Large Cell Lymphoma

0 | Mar 15 2017

Ceccon M et al. found the knowledge of the possible appearance of new clinically relevant mechanisms of drug resistance is a useful tool for the management of new TKI-resistant cases. [Read the Full Post]

Vorinostat Enhances Cytotoxicity of SN-38 and Temozolomide in Ewing Sarcoma Cells and Activates STAT3/AKT/MAPK Pathways

0 | Mar 13 2017

Sampson VB et al suggested that potent antiproliferative and proapoptotic activity were demonstrated for ST induced DNA damage before or simultaneous with HDAC inhibition and cell death was mediated through the p53 pathway. These observations may aid in designing new protocols for treating pediatric patients with high-risk EWS. [Read the Full Post]

GRP78 confers the resistance to 5-FU by activating the c-Src/LSF/TS Axis in hepatocellular carcinoma

1329 | Mar 11 2017

Gu YJ, et al. further identified that GRP78 interacts physically with c-Src through its ATPase domain and promotes the phosphorylation of c-Src, which in turn increases the expression of LSF in the nucleus. Together, GRP78 confers the resistance to 5-FU by up-regulating the c-Src/LSF/TS axis via its ATPase domain. [Read the Full Post]

Hydrogen sulfide suppresses endoplasmic reticulum stress-induced endothelial-to-mesenchymal transition through Src pathway

0 | Mar 08 2017

Ying R et al. revealed that H2S could protect against ER stress-induced EndMT through Src pathway, which may be a novel role for the cardioprotection of H2S. [Read the Full Post]

Insulin-like growth factor I promotes oocyte maturation through increasing the expression and phosphorylation of epidermal growth factor receptor in the zebrafish ovary

0 | Mar 04 2017

Xie L et al. lighted on the cross-talk between two important growth factors in the zebrafish ovary and the mechanism underlying the IGF-I induction on oocyte maturation. [Read the Full Post]

Targeting Non-Small Cell Lung Cancer Cells by Dual Inhibition of the Insulin Receptor and the Insulin-Like Growth Factor-1 Receptor

0 | Mar 02 2017

Vincent EE et al. concluded that small molecule inhibitors targeting both the IR and IGF1R more effectively reduce NSCLC cell proliferation in a manner independent of the IR:IGF1R expression ratio, providing a therapeutic rationale for the treatment of this disease. [Read the Full Post]

EMT is associated with, but does not drive resistance to ALK inhibitors among EML4-ALK non-small cell lung cancer

1563 | Feb 08 2017

This study warrants more exploration of HSP90 inhibitors for ALK-positive patients who progress on 1st and 2nd line ALK inhibitor therapy. [Read the Full Post]

Mechanisms of Acquired Resistance to AZD9291 A Mutation-Selective, Irreversible EGFR Inhibitor

2164 | Feb 06 2017

Kim TM, et al.'s result shows that Acquired resistance mechanisms of AZD9291 in patients with EGFR-mutant NSCLC who failed treatment with first-generation EGFR TKIs include the loss of EGFR-mutant clones plus alternative pathway activation or histologic transformation and EGFR ligand-dependent activation. [Read the Full Post]

EGFR Exon 18 Mutations in Lung Cancer: Molecular Predictors of Augmented Sensitivity to Afatinib or Neratinib as Compared with First- or Third-Generation TKIs

2042 | Feb 05 2017

Kobayashi Y, et al.’‘s result shows that’Lung cancers harboring exon 18 mutations should not be overlooked in clinical practice. These cases can be best treated with afatinib or neratinib, although the currently available in vitro diagnostic kits cannot detect all exon 18 mutations [Read the Full Post]

Signaling through the Phosphatidylinositol 3-Kinase (PI3K)/ Mammalian Target of Rapamycin (mTOR) Axis is Responsible for Aerobic Glycolysis mediated by Glucose Transporter in Epidermal Growth Factor Receptor (EGFR)-mutated Lung Adenocarcinoma

1492 | Feb 04 2017

Makinoshima H, et al.‘s results suggest that PI3K/AKT/mTOR signaling is indispensable for the regulation of aerobic glycolysis in EGFR-mutated LAD cells. [Read the Full Post]

Tivantinib induces G2/M arrest and apoptosis by disrupting tubulin polymerization in hepatocellular carcinoma

1109 | Jan 24 2017

Xiang Q, et al.'s conclusion shows that the potent anti-tumor activity of tivantinib in HCC was achieved by targeting microtubule. Tivantinib treatment for patients with HCC should not be selected based on MET status. [Read the Full Post]

Treatment Efficacy and Resistance Mechanisms Using the Second-Generation ALK Inhibitor AP26113 in Human NPM-ALK–Positive Anaplastic Large Cell Lymphoma

2364 | Jan 23 2017

Ceccon M, et al.'s knowledge of the possible appearance of new clinically relevant mechanisms of drug resistance is a useful tool for the management of new TKI-resistant cases. [Read the Full Post]

Vorinostat Enhances Cytotoxicity of SN-38 and Temozolomide in Ewing Sarcoma Cells and Activates STAT3/AKT/MAPK Pathways

0 | Jan 21 2017

In Sampson VB, et al.'s summary, potent antiproliferative and proapoptotic activity were demonstrated for ST induced DNA damage before or simultaneous with HDAC inhibition and cell death was mediated through the p53 pathway. These observations may aid in designing new protocols for treating pediatric patients with high-risk EWS. [Read the Full Post]

Targeting non-small cell lung cancer cells by dual inhibition of the insulin receptor and the insulin-like growth factor-1 receptor

1712 | Jan 16 2017

Vincent EE et al. concluded that small molecule inhibitors targeting both the IR and IGF1R more effectively reduce NSCLC cell proliferation in a manner independent of the IR:IGF1R expression ratio, providing a therapeutic rationale for the treatment of this disease. [Read the Full Post]

EMT is associated with, but does not drive resistance to ALK inhibitors among EML4-ALK non-small cell lung cancer

1366 | Jan 03 2017

The study of Mol Oncol's warrants more exploration of HSP90 inhibitors for ALK-positive patients who progress on 1st and 2nd line ALK inhibitor therapy. [Read the Full Post]

Signaling through the Phosphatidylinositol 3-Kinase (PI3K)/Mammalian Target of Rapamycin (mTOR) Axis Is Responsible for Aerobic Glycolysis mediated by Glucose Transporter in Epidermal Growth Factor Receptor (EGFR)-mutated Lung Adenocarcinoma

1585 | Jan 02 2017

Makinoshima H et al. suggested that PI3K/AKT/mTOR signaling is indispensable for the regulation of aerobic glycolysis in EGFR-mutated LAD cells. [Read the Full Post]

EGFR Exon 18 Mutations in Lung Cancer: Molecular Predictors of Augmented Sensitivity to Afatinib or Neratinib as Compared with First- or Third-Generation TKIs

1786 | Jan 02 2017

Lung cancers harboring exon 18 mutations should not be overlooked in clinical practice. These cases can be best treated with afatinib or neratinib, although the currently available in vitro diagnostic kits cannot detect all exon 18 mutations. [Read the Full Post]

Mechanisms of Acquired Resistance to AZD9291 A Mutation-Selective, Irreversible EGFR Inhibitor

2338 | Dec 30 2016

Acquired resistance mechanisms of AZD9291 in patients with EGFR-mutant NSCLC who failed treatment with first-generation EGFR TKIs include the loss of EGFR-mutant clones plus alternative pathway activation or histologic transformation and EGFR ligand-dependent activation. [Read the Full Post]

MET Inhibition in Clear Cell Renal Cell Carcinoma

1956 | Dec 23 2016

Xie Z et al. provide further preclinical rationale for dual MET/VEGFR2 inhibition in ccRCC. [Read the Full Post]

Inhibition of spleen tyrosine kinase activation ameliorates inflammation, cell death, and steatosis in alcoholic liver disease

1658 | Dec 17 2016

Bukong TN et al. demonstrated a novel, functional, and multicellular role for SYK phosphorylation in modulating immune cell-driven liver inflammation, hepatocyte cell death, and steatosis at different stages of ALD. [Read the Full Post]

Reconstructing the temporal progression of HIV-1 immune response pathways

2048 | Dec 13 2016

Jain S et al. experimentally validated several of TimePaths' predictions highlighting the usefulness of temporal models. [Read the Full Post]

Substitution scanning identifies a novel, catalytically active ibrutinib-resistant BTK cysteine 481 to threonine (C481T) variant

1156 | Dec 11 2016

Hamasy A et al. identified three potential ibrutinib resistance scenarios for cysteine 481 replacement: (1) Serine, being catalytically active and therefore predominating among patients. (2) Threonine, also being catalytically active, but predicted to be scarce, because two nucleotide changes are needed. (3) As BTK variants replaced with other residues are catalytically inactive, they presumably need compensatory mutations, therefore being very scarce. [Read the Full Post]

Involvement of PARK2-Mediated Mitophagy in Idiopathic Pulmonary Fibrosis Pathogenesis

2547 | Dec 02 2016

Kobayashi K et al. suggested that insufficient mitophagy-mediated PDGFR/PI3K/AKT activation, which is mainly attributed to reduced PARK2 expression, is a potent underlying mechanism for myofibroblast differentiation and proliferation in fibroblastic foci formation during IPF pathogenesis. [Read the Full Post]

Basic FGF and PDGF-BB synergistically stimulate hyaluronan and IL-6 production by orbital fibroblasts

4417 | Nov 26 2016

Multi-target therapy directed at the bFGF and PDGF pathways may potentially be of interest for the treatment of GO. [Read the Full Post]

Diverse, Biologically Relevant, and Targetable Gene Rearrangements in Triple-Negative Breast Cancer and Other Malignancies

2088 | Nov 21 2016

Shaver TM et al. identified highlight the importance of considering noncoding gene rearrangement partners, and the targetable gene fusions identified in TNBC demonstrate the need to advance gene fusion detection for molecularly heterogeneous cancers. [Read the Full Post]

Isocitrate Dehydrogenase Mutations Confer Dasatinib Hypersensitivity and SRC Dependence in Intrahepatic Cholangiocarcinoma

3716 | Nov 16 2016

Saha SK et al. showed that IDHm ICC cells have a unique dependency on SRC and suggested that dasatinib may have therapeutic benefit against IDHm ICC. [Read the Full Post]

Antitumor effect of FGFR inhibitors on a novel cholangiocarcinoma patient derived xenograft mouse model endogenously expressing an FGFR2-CCDC6 fusion protein

1816 | Nov 09 2016

Wang Y et al. provides a strong rationale for the investigation of FGFR inhibitors, particularly BGJ398, as a therapeutic option for cholangiocarcinoma patients harboring FGFR2 fusions. [Read the Full Post]

Synergistic effect of pacritinib with erlotinib on JAK2-mediated resistance in epidermal gowth factor receptor mutation-positive non-small cell lung Cancer

2192 | Oct 25 2016

Ochi N et al. found that pacritinib combined with EGFR-TKI might be a potent strategy against JAK2-mediated EGFR-TKI resistance. [Read the Full Post]

Epidermal growth factor receptor inhibitor cancer drug gefitinib modulates cell growth and differentiation of acute myeloid leukemia cells via histamine receptors

1528 | Oct 25 2016

Yadav M et al. found that HRs play critical roles in anti-cancer effects of gefitinib in both EGFR-deficient and EGFR-rich environments. [Read the Full Post]

ErbB2-dependent downregulation of a pro-apoptotic protein Perp is required for oncogenic transformation of breast epithelial cells

2714 | Oct 14 2016

Khan IA et al. identified a novel mechanism of ErbB2-mediated mechanism of anoikis resistance of ErbB2-overproducing breast epithelial cells. [Read the Full Post]

EGFR Activation Leads to Cell Death Independent of PI3K/AKT/mTOR in an AD293 Cell Line

2750 | Oct 14 2016

Treda C et al. showed another EGFR function, dependent on environmental factors, which could be employed in therapy and drug design. [Read the Full Post]

Hiding inside? Intracellular expression of non-glycosylated c-kit protein in cardiac progenitor cells

3509 | Oct 13 2016

Shi H et al. demonstrated for the first time that c-kit is not only expressed in CDCs but may also directly participate in CDC differentiation into an endothelial lineage. [Read the Full Post]

BAG3-mediated Mcl-1 stabilization contributes to drug resistance via interaction with USP9X in ovarian cancer

1687 | Oct 11 2016

Habata S et al. suggested that inhibiting BAG3 in addition to anti-apoptotic Bcl-2 family proteins may be a useful therapeutic strategy for the treatment of chemoresistant ovarian cancers. [Read the Full Post]

Src as a Therapeutic Target in Biliary Tract Cancer

1697 | Oct 10 2016

Nam AR et al. suggested that Src might be a potential therapeutic target in BTC. [Read the Full Post]

Constructing and Validating High-Performance MIEC-SVM Models in Virtual Screening for Kinases: A Better Way for Actives Discovery

2245 | Oct 10 2016

Sun H et al. showed that the optimized MIEC-SVM model, which identified 7 actives with IC50 < 10 μM from 50 purchased compounds and performed much better than Autodock, suggesting that the proposed strategy is a powerful tool in structure-based virtual screening. [Read the Full Post]

Utilising the EGFR interactome to identify mechanisms of drug resistance in non-small cell lung cancer - Proof of concept towards a systems pharmacology approach

2259 | Oct 08 2016

Saafan H et al. identified that differential proteins in the EGFR interactome of HCC4006rERLO0.5 cells could be related to multiple resistance mechanisms including alterations in growth factor receptor expression, cellular remodelling processes suggesting epithelial-to-mesenchymal transition as well as alterations in downstream signalling. [Read the Full Post]

EGFR inhibitors identified as a potential treatment for chordoma in a focused compound screen

2565 | Sep 30 2016

Scheipl S et al. provided evidence for exploring the efficacy of EGFR inhibitors in the treatment of patients with chordoma and studying possible resistance mechanisms to these compounds in vitro and in vivo. [Read the Full Post]

Neuritin Mediates Activity-Dependent Axonal Branch Formation in Part via FGF Signaling

2095 | Sep 29 2016

Shimada T, et al. revealed the molecular mechanism underlying mossy fiber sprouting. [Read the Full Post]

Lassa Virus Cell Entry via Dystroglycan Involves an Unusual Pathway of Macropinocytosis

2037 | Sep 22 2016

Oppliger J et al. revealed novel fundamental aspects of the LASV-host cell interaction and highlights a possible candidate drug target for therapeutic intervention. [Read the Full Post]

Phosphatidylinositol 3-Kinase/Akt Mediates Integrin Signaling To Control RNA Polymerase I Transcriptional Activity

2649 | Sep 12 2016

Wu C et al. revealed that a pivotal role of integrin signaling in regulation of RNA polymerase I transcriptional activity and shed light on the downstream signaling axis that participates in regulation of this key aspect of cell growth. [Read the Full Post]

Metabolic alterations and drug sensitivity of tyrosine kinase inhibitor resistant leukemia cells with a FLT3/ITD mutation

0 | Sep 08 2016

Huang A, et al. revealed a metabolic signature of sorafenib-resistant cells and suggests that glycolytic inhibition may override such resistance and warrant further clinical investigation. [Read the Full Post]

Targeting FGFR2 with alofanib (RPT835) shows potent activity in tumour models

1617 | Sep 08 2016

Tsimafeyeu I, et al. found that alofanib is a potent FGFR2 inhibitor and provide strong rationale for its evaluation in patients with FGFR2-driven cancers. [Read the Full Post]

Hydrogen sulfide suppresses endoplasmic reticulum stress-induced endothelial-to-mesenchymal transition through Src pathway

1536 | Sep 02 2016

Ying R, et al. revealed that H2S could protect against ER stress-induced EndMT through Src pathway, which may be a novel role for the cardioprotection of H2S. [Read the Full Post]

Insulin-like growth factor I promotes oocyte maturation through increasing the expression and phosphorylation of epidermal growth factor receptor in the zebrafish ovary

1194 | Sep 01 2016

Xie L, et al. sheded light on the cross-talk between two important growth factors in the zebrafish ovary and the mechanism underlying the IGF-I induction on oocyte maturation. [Read the Full Post]

Tcfap2c acts as a key factor in mammary tumorigenesis

4042 | Mar 27 2015

Park et al. conducted a serious experiments to gain greater insight into functions of TFAP2C on mammary tumorigeneisis in MMTV-Neu transgenic female mice. [Read the Full Post]

GPRC5A directly inhibits EGFR signaling to suppress lung tumorigenesis

5164 | Mar 20 2015

Zhong et al. revealed that GPRC5A negatively regulates EGFR signaling and its downstream signaling STAT3. [Read the Full Post]

The anti-inflammatory effect of IL-37-IL-1R8-IL-18Rα complex

2178 | Mar 17 2015

Nold-Petry et al. identified the endogenous ligand-receptor complex IL-37-IL-1R8-IL-18Rα. [Read the Full Post]

Molecular changes of the transformation of NSCLC to SCLC TKI-resistant EGFR mutant cancers

4018 | Mar 16 2015

Niederst et al. demonstrated the molecular changes occur in NSCLC to small-cell lung cancer (SCLC) transformed TKI-resistant EGFR mutant cancers. [Read the Full Post]

AXL regulates cetuximab resistance in HNSCC and NSCLC

5488 | Mar 13 2015

Brand et al. demonstrated that AXL-EGFR signaling positive feedback loop is one of the mechanism of developing cetuximab resistance. [Read the Full Post]

αB-crystallin induces by matrix detachment via ERK is critical in inhibition of anoikis

6486 | Mar 05 2015

Malin et al. identified an matrix detachment-induced antiapoptotic molecular chaperone, αB-crystallin, confers anoikis resistance. [Read the Full Post]

Inactivating mutations of SMARCE1 promotes EGFR expression and suppress the responses to MET and ALK inhibitors in lung cancer

5615 | Feb 26 2015

The study conducted by Papadakis et al. showed inactivating mutations in SMARCE1 gene, which encodes SWI/SNF subunit, upregulate EGFR expression and induce resistance to MET and ALK inhibitors in non-small cell lung cancers (NSCLCs). [Read the Full Post]

A novel role of Semaphorin3A on the increase of vascular permeability

5298 | Jan 28 2015

Hou et al. identified Semaphorin3A (Sema3A) as a critical factor mediates vascular permeability and contributes to ischemic brain damage. [Read the Full Post]

ESKM, a novel therapeutic agent for sensitive and resistant PH+ leukemias

12285 | Jan 23 2015

Dubrovsky et al. developed an antibody, ESKM, which is therapeutically effective on acute and chronic leukemias in murine models. [Read the Full Post]

The new finding of PI3K signaling regulation provides a novel therapeutic strategy for luminal breast cancer

7086 | Jan 15 2015

Costa et al. found the high efficiency of p110α inhibition by BYL719 is attenuated due to p110β accumulation. [Read the Full Post]

The mechanism of kinase independent AKT in promoting cancer development

5024 | Jan 12 2015

Vivanco et al. revealed the mechanism and emphasized a kinase-independent function of AKT in regulating cancer cell survival. [Read the Full Post]

An unusual mechanism of ERBB4 in regulating tumor related gene expression

7966 | Jan 06 2015

Haskins et al. found ERBB4 activated the transcriptional coactivator YAP by binding to its ligand neuregulin 1 (NRG1), to regulate gene expression of cancer cells. [Read the Full Post]

Two states of BRAFV600 mutant melanoma that related to MAPK inhibition resistance

6100 | Dec 31 2014

Konieczkowski et al. revealed the mechanism of MAPK inhibition on BRAFV600 mutant melanomas. [Read the Full Post]

ABL1, a new target of oxidative stress related rental cancer

4616 | Dec 19 2014

Sourbier et al. used hereditary kidney cancers as a model to investigate mechanism-based therapeutic interventions by metabolic adaptations. They found the activation of ABL1, an proto-oncogene, is critical in tumors that relate to glycolysis and oxidative stress. [Read the Full Post]

The HGF/cMET signaling promotes angiogenesis in bone marrow endothelial cells

2178 | Dec 10 2014

Ferrucci et al. demonstrated hepatocyte growth factor (HGF)/mesenchymal-epithelial transition factor (cMET) pathway plays an important role in regulation angiogenesis. [Read the Full Post]

VEFG/SphK pathway plays an important role in Niemann-Pick type C disease

3720 | Dec 03 2014

Lee et al. identified the defective of sphingosine kinase (SphK) and vascular endothelial growth factor (VEGF) activities are main signaling that promotes sphingosine storage. [Read the Full Post]

KIAA1199 provides a connection between oncogenic signaling of NF-κB and EGFR

5246 | Dec 01 2014

Shostak et al. showed the connection between the two oncogenic cascades by identifying a key factor, KIAA1199, that associated with human papillomavirus (HPV) infection. [Read the Full Post]

The mechanism of drug resistance in BRAF (V600E) mutant melanoma

8242 | Nov 19 2014

Sun et al. demonstrated the resistance of BRAF (V600E) is reversible and adaptive. The process involves several transduction factors, such as EGFR, PDGFRB, TGF-β, and SOX10. [Read the Full Post]

Combination of PI3K/mTOR and EGFR inhibitors suppresses KRAS-mutant colorectal cancer

5942 | Nov 14 2014

Belmont et al. demonstrated combination of PI3K/mTOR and EGFR inhibitors may become a novel therapy in patients with KRAS-mutant CRC. [Read the Full Post]

FGF21 is not required for CR-mediated IGF-1 reduction or cell proliferation inhibition

6825 | Nov 06 2014

Thompson et al. found that, in response to moderate CR, phosphorylated STAT5 may act as a key molecule, and FGF21 was not required for the down-regulation of IGF-1 expression level or cell proliferation rates. [Read the Full Post]

Targeting ALK and ERK5 is a new strategy for neuroblastoma treatment

3819 | Nov 04 2014

Umapathy et al. found kinase ERK5 regulates Anaplastic lymphoma kinase (ALK) induced MYCN transcription and proliferation of neuroblastoma. The results indicates that combination therapy of inhibiting ALK and ERK5 may be a novel strategy for ALK-positive neuroblastoma patients. [Read the Full Post]

Endocrine therapy has become the most important systemic treatment

4204 | Mar 10 2014

Imatinib is a multi-target inhibitor of v-Abl, c-Kit and PDGFR with IC50 of 0.6 μM, 0.1 μM and 0.1 μM, respectively. [Read the Full Post]

Afatinib is a drug approved in much of the world

3806 | Mar 07 2014

BIBW2992 shows potent activity against both wild-type and mutant forms of EGFR and HER2. [Read the Full Post]

Linifanib is a structurally novel potent inhibitor of RTK

3205 | Mar 03 2014

Linifanib shows inhibitory to Kit, PDGFRβ and Flt4 with IC50 of 14 nM, 66 nM and 190 nM in kinases assay. [Read the Full Post]

E7080 is a multi kinase inhibitor that is being investigated for the treatment of various

3482 | Feb 27 2014

E7080 (Lenvatinib) is a multi-target inhibitor, mostly for VEGFR2(KDR)/VEGFR3(Flt-4) with IC50 of 4 nM/5.2 nM, less potent against VEGFR1/Flt-1, ~10-fold more selective for VEGFR2/3 against FGFR1, PDGFRα/β. Phase 3. [Read the Full Post]

BGJ398 is a potent and selective FGFR inhibitor for FGFR

3574 | Feb 21 2014

BGJ398 also prevents VEGFR2 with low potency. [Read the Full Post]

Linifanib is a structurally novel potent inhibitor of receptor tyrosine kinases

3176 | Feb 20 2014

Linifanib shows inhibitory to Kit, PDGFRβ and Flt4 with IC50 of 14 nM, 66 nM and 190 nM in kinases assay. [Read the Full Post]

Dovitinib is currently under clinical investigation for hepatocellular carcinoma

3505 | Feb 19 2014

Dovitinib potently inhibits the FGF-stimulated growth of WT and F384L-FGFR3-expressing B9 cells with IC50 of 25 nM. [Read the Full Post]

Cediranib is currently in double blind studies for the treatment

3394 | Feb 18 2014

Cediranib (AZD2171) is a highly potent VEGFR(KDR) inhibitor with IC50 of <1 nM, also inhibits Flt1/4 with IC50 of 5 nM/≤3 nM [Read the Full Post]

ARQ197 is a staurosporine derivative that binds to the dephosphorylated MET kinase

2436 | Feb 18 2014

Tivantinib (ARQ 197) is the first non-ATP-competitive c-Met inhibitor with Ki of 0.355 μM, little activity to Ron, and no inhibition to EGFR. [Read the Full Post]

XL184 is a small molecule inhibitor of the tyrosine kinases

3126 | Feb 14 2014

XL184 has weak inhibitory activity against RON and PDGFRβ with IC50 of 124 nM and 234 nM [Read the Full Post]

Cediranib is a potent inhibitor of vascular endothelial growth factor

3464 | Feb 10 2014

Cediranib suppresses PDGF-AA with IC50 of 0.04 μM in MG63 cell lines. [Read the Full Post]

Bosutinib is a tyrosine kinase inhibitor undergoing research

3527 | Feb 10 2014

Bosutinib (SKI-606) is a novel, dual Src/Abl inhibitor with IC50 of 1.2 nM and 1 nM, respectively. [Read the Full Post]

Dasatinib is being evaluated for use in numerous other cancers

3447 | Feb 08 2014

Dasatinib is more effective than imatinib in inhibiting the proliferation of Ba/F3 cells expressing wild-type Bcr-Abl and Bcr-Abl mutants. [Read the Full Post]

We describe the mechanism of action of WP1130

0 | Feb 08 2014

WP1130 is a selective deubiquitinase inhibitor. [Read the Full Post]

MP 470 is a potent and multi targeted inhibitor

2091 | Jan 29 2014

Amuvatinib (MP-470) is a potent and multi-targeted inhibitor of c-Kit, PDGFRα and Flt3 with IC50 of 10 nM, 40 nM and 81 nM, respectively. [Read the Full Post]

E7080 is a multi kinase inhibitor that is being investigated

2657 | Jan 24 2014

E7080, as a potent inhibitor of in vitro angiogenesis, shows a significantly inhibitory effect on VEGF/KDR and SCF/Kit signaling. [Read the Full Post]

We describe the mechanism of action of WP1130

4674 | Jan 22 2014

WP1130 (Degrasyn) is a selective deubiquitinase (DUB: USP5, UCH-L1, USP9x, USP14, and UCH37) inhibitor and also suppresses Bcr/Abl, also a JAK2 transducer (without affecting 20S proteasome) and activator of transcription (STAT). [Read the Full Post]

XL184 is currently undergoing clinical trials for the treatment of prostate

2649 | Jan 21 2014

XL184 has weak inhibitory activity against RON and PDGFRβ with IC50 of 124 nM and 234 nM, respectivey, and has low activity against FGFR1 with IC50 of 5.294 μM. [Read the Full Post]

PCI 32765 is an anticancer drug targeting B cell malignancies

3456 | Jan 20 2014

PCI-32765 shows the potent and irreversible inhibitory effect and selectivity for Btk enzymatic activity. [Read the Full Post]

Bafetinib is a dual Bcr Abl and Lyn kinase inhibitor

3490 | Jan 15 2014

Bafetinib (INNO-406) is a potent and selective dual Bcr-Abl/Lyn inhibitor with IC50 of 5.8 nM/19 nM, does not inhibit the phosphorylation of the T315I mutant and is less potent to PDGFR and c-Kit. Phase 2. [Read the Full Post]

OSI 930 is a novel inhibitor of the receptor tyrosine kinases Kit

0 | Jan 13 2014

OSI-930 inhibits the cell proliferation in the HMC-1 cell line with IC50 of 14 nM without significant effect on growth of the COLO-205 cell line that does not express a constitutively active mutant receptor tyrosine kinase. [Read the Full Post]

AZD0530 is a dual specific inhibitor of Src and Abl

3382 | Jan 13 2014

Saracatinib also potently inhibits other Src tyrosine kinase family members including c-Yes, Fyn, Lyn, Blk, Fgr, and Lck with IC50 from 4-10 nM. [Read the Full Post]

Bafetinib is a second generation tyrosine kinase inhibitor

3385 | Jan 06 2014

Bafetinib blocks WT Bcr-Abl autophosphorylation and its downstream kinase activity with IC50 of 11 nM and 22 nM in K562 and 293T cells [Read the Full Post]

Dasatinib is a rescription medicine used to treat adults

3046 | Dec 25 2013

Dasatinib is a novel, potent and multi-targeted inhibitor that targets Abl, Src and c-Kit, with IC50 of <1 nM, 0.8 nM and 79 nM, respectively. [Read the Full Post]

Neratinib is a highly selective HER2 and EGFR inhibitor

2972 | Dec 25 2013

Neratinib weakly inhibits tyrosine kinases KDR and Src with IC50 of 0.8 μM and 1.4 μM, respectively, being 14- and 24-fold less active compared with HER2. [Read the Full Post]

Dasatinib is a cancer drug produced by Bristol Myers Squibb

3386 | Dec 23 2013

Dasatinib is a novel, potent and multi-targeted inhibitor that targets Abl, Src and c-Kit, with IC50 of <1 nM, 0.8 nM and 79 nM, respectively. [Read the Full Post]

AZD0530 is a dually active inhibitor of c Src and Bcr ABL

2834 | Dec 18 2013

Saracatinib (AZD0530) is a potent Src inhibitor with IC50 of 2.7 nM, and potent to c-Yes, Fyn, Lyn, Blk, Fgr and Lck; less active for Abl and EGFR (L858R and L861Q). [Read the Full Post]

OSI 930 is a novel inhibitor of the receptor tyrosine kinases Kit and kinase

2193 | Dec 12 2013

OSI-930 inhibits the cell proliferation in the HMC-1 cell line with IC50 of 14 nM without significant effect on growth of the COLO-205 cell line that does not express a constitutively active mutant receptor tyrosine kinase. [Read the Full Post]

Tandutinib is a small molecule inhibitor of the type

3400 | Dec 09 2013

Tandutinib has little activity against EGFR, FGFR, KDR, InsR, Src, Abl, PKC, PKA and MAPKs. [Read the Full Post]

MP 470 is a potent and multi targeted inhibitor of c Kit

2086 | Dec 06 2013

In mice xenograft models of HT-29, A549, and SB-CL2 cells, MP-470 (10 mg/kg–75 mg/kg via i.p. or 50 mg/kg–200 mg/kg via p.o.) inhibits tumor growth. [Read the Full Post]

BGB324 is a novel oral highly selective small molecule inhibitor

2992 | Dec 05 2013

R428 blocks the catalytic and procancerous activities of Axl. R428 inhibits Axl with low nanomolar activity and blocks Axl-dependent events [Read the Full Post]

Gefitinib is used to treat non small cell lung cancer in people

3891 | Dec 04 2013

Gefitinib (ZD-1839) is an EGFR inhibitor for Tyr1173, Tyr992, Tyr1173 and Tyr992 in the NR6wtEGFR and NR6W cells with IC50 of 37 nM, 37nM, 26 nM and 57 nM, respectively. [Read the Full Post]

Dovitinib is a small molecule multitargeted receptor tyrosine kinase inhibitor

3675 | Nov 27 2013

Dovitinib potently inhibits the FGF-stimulated growth of WT and F384L-FGFR3-expressing B9 cells with IC50 of 25 nM. [Read the Full Post]

Cediranib is a potent inhibitor of vascular endothelial growth factor receptor tyrosine kinases

2325 | Nov 25 2013

Cediranib inhibits VEGF-stimulated proliferation with IC50 of 0.4 nM. Cediranib suppresses PDGF-AA with IC50 of 0.04 μM in MG63 cell lines. [Read the Full Post]

NVP BHG712 is a specific EphB4 inhibitor with ED50 of 25 nM

2546 | Nov 18 2013

NVP-BHG712 is a specific EphB4 inhibitor with ED50 of 25 nM that discriminates between VEGFR and EphB4 inhibition . [Read the Full Post]

R428 inhibits angiogenesis in corneal micropocket and tumor models

3982 | Nov 13 2013

R428 is an inhibitor of Axl with IC50 of 14 nM, >100-fold selective for Axl versus Abl. Selectivty for Axl is also greater than Mer and Tyro3 and InsR, EGFR, HER2, and PDGFRβ. [Read the Full Post]

Dasatinib is a novel potent and multi targeted inhibitor

2517 | Nov 11 2013

Dasatinib is more effective than imatinib in inhibiting the proliferation of Ba/F3 cells expressing wild-type Bcr-Abl and Bcr-Abl mutants, with the exception of T315I. [Read the Full Post]

OSI 930 is an inhibitor of the receptor tyrosine kinases c Kit

2297 | Nov 08 2013

OSI-930 inhibits the cell proliferation in the HMC-1 cell line with IC50 of 14 nM without significant effect on growth of the COLO-205 cell line that does not express a constitutively active mutant receptor tyrosine kinase. [Read the Full Post]

Nilotinib is a tyrosine kinase inhibitor approved for the treatment of chronic myelogenous leukemia

2297 | Nov 07 2013

Nilotinib inhibits proliferation, migration, and actin filament formation, as well as the expression of α-SMA and collagen in activated HSCs. [Read the Full Post]

WP1130 is a novel selective small molecular deubiquitinase

2330 | Nov 06 2013

Administration of WP1130 inhibits the growth of K562 tumors as well as both wildtype Bcr/Abl and T315I mutant Bcr/Abl-expressing BaF/3 cells transplanted into nude mice. [Read the Full Post]

XL184 is a small molecule inhibitor of the tyrosine kinases c Met

2362 | Nov 01 2013

XL184 has weak inhibitory activity against RON and PDGFRβ with IC50 of 124 nM and 234 nM, respectivey, and has low activity against FGFR1 with IC50 of 5.294 μM. [Read the Full Post]

Nilotinib is indicated for the treatment of adult patients

2231 | Oct 31 2013

Nilotinib inhibits proliferation, migration, and actin filament formation, as well as the expression of α-SMA and collagen in activated HSCs. Nilotinib induces apoptosis of HSCs, which is correlated with reduced bcl-2 expression. [Read the Full Post]

OSI 930 is a novel inhibitor of the receptor tyrosine kinases Kit

2490 | Oct 22 2013

OSI-930 inhibits the cell proliferation in the HMC-1 cell line with IC50 of 14 nM without significant effect on growth of the COLO-205 cell line that does not express a constitutively active mutant receptor tyrosine kinase. [Read the Full Post]

Neratinib is a tyrosine kinase inhibitor under investigation

2487 | Oct 21 2013

Neratinib weakly inhibits tyrosine kinases KDR and Src with IC50 of 0.8 μM and 1.4 μM, respectively, being 14- and 24-fold less active compared with HER2. [Read the Full Post]

PHA 665752 is a potent selective and ATP competitive c Met inhibitor

2407 | Oct 17 2013

PHA-665752 significantly inhibits c-Met kinase activity with Ki of 4 nM, and exhibits >50-fold selectivity for c-Met compared with various tyrosine and serine-threonine kinases. [Read the Full Post]

ARQ197 has been shown to prevent HGF induced cellular responses

2510 | Aug 26 2013

ARQ-197 is the first non-ATP-competitive c-Met inhibitor withKi of 0.355 μM [Read the Full Post]

Sunitinib was the first cancer drug simultaneously

2637 | Aug 06 2013

Sunitinib inhibits VEGF-dependent VEGFR2 phosphorylation and PDGF-dependent PDGFRβ phosphorylation with IC50 of 10 nM and 10 nM, respectively. [Read the Full Post]

Masitinib is a tyrosine kinase inhibitor used in the treatment of mast cell tumors in animals

2655 | Jul 03 2013

Masitinib is a competitive inhibitor against ATP at concentrations ≤500 nM. Masitinib also potently inhibits recombinant PDGFR and the intracellular kinase Lyn, and to a lesser extent, fibroblast growth factor receptor 3. [Read the Full Post]

Tivantinib- is an oral triphosphate competitive cMET inhibitor

2589 | Jun 28 2013

ARQ-197 has been shown to prevent HGF/c-met induced cellular responses in vitro. ARQ-197 possesses antitumor activity; inhibiting proliferation of A549. [Read the Full Post]

XL-184 is a new chemical entity that inhibits VEGFR2

2521 | Jun 26 2013

XL184 has weak inhibitory activity against RON and PDGFRβ with IC50 of 124 nM and 234 nM, respectivey, and has low activity against FGFR1 with IC50 of 5.294 μM. [Read the Full Post]

Motesanib is an experimental drug candidate

2667 | May 16 2013

Motesanib Diphosphate has broad activity against the human VEGFR family, and displays >1000 selectivity against EGFR, Src, and p38 kinase. [Read the Full Post]

Nilotinib was approved as Tasigna in the America

2785 | Apr 24 2013

Nilotinib inhibits proliferation, migration, and actin filament formation, as well as the expression of α-SMA and collagen in activated HSCs. Nilotinib induces apoptosis of HSCs, which is correlated with reduced bcl-2 expression, increases p53 expression, cleavage of PARP, as well as increases expression of PPARγ and TRAIL-R. Nilotinib also induces cell cycle arrest, accompanied by increased expression of p27 and downregulation of cyclin D1. [Read the Full Post]

Sunitinib inhibits cellular signaling by targeting multiple receptor tyrosine kinases

2674 | Apr 08 2013

These include all receptors for platelet-derived growth factor (PDGF-Rs) and vascular endothelial growth factor receptors (VEGFRs), which play a role in both tumor angiogenesis and tumor cell proliferation. [Read the Full Post]

Quizartinib is currently under development for the treatment of acute myeloid leukaemia

3775 | Apr 03 2013

Quizartinib (AC220) is a small molecule receptor tyrosine kinase inhibitor that is currently under development for the treatment of acute myeloid leukaemia. Its molecular target is FLT3, also known as CD135 which is a proto-oncogene. [Read the Full Post]

Sunitinib was the first cancer drug simultaneously approved for two different indications

2500 | Apr 01 2013

Sunitinib Malate (Sutent, SU11248) is a multi-targeted RTK inhibitor targeting VEGFR2 (Flk-1) and PDGFRβ with IC50 of 80 nM and 2 nM, and also inhibits c-Kit. [Read the Full Post]

Src inhibitors are promising therapy molecules for human cervical carcinomas

2656 | Jan 22 2013

Candida albicans is responsible for approximately 50% of all human life-threatening nosocomial fungal infections . Completion of its diploid genome sequence now provides a foundation for studies on C. albicans biology and SRC Inhibitors pathogenesis, and offers new opportunities for therapeutic intervention. [Read the Full Post]

ALK inhibitors are potential anti cancer drugs that act on tumours with variations

2572 | Dec 19 2012

The ALK (anaplastic lymphoma kinase) gene encodes a tyrosine kinase belonging to the insulin receptor superfamily. ALK is abundantly expressed in neural tissue during embryogenesis, but levels fall during early development, so that in adults it is expressed only in rare scattered neural cells (Iwahara et al., 1997; Morris et al., 1997; Webb et al., 2009; Ardini et al., 2010). [Read the Full Post]

ALK Inhibitors has been recognized leading to the reorganization

3823 | Dec 05 2012

The significance of transition from preclinical to clinical studies has been recognized leading to the re-organization of research units into ALK Inhibitors translational groups bringing involved disciplines closer together. The intent is to leverage basic science to better support the translation of in vitro and in vivo preclinical data into clinical decisions [Read the Full Post]

Gefitinib were not considered clinically relevant

4651 | Nov 15 2012

There were no statistically significant differences in the mean percent baseline slopes over the 6 h of testing, and any Gefitinib differences were not considered clinically relevant [Read the Full Post]

Inhibition of KSP affects the formation of the bipolar spindle

4156 | Oct 30 2012

Inhibition of KSP affects the formation of the bipolar spindle for the separation and purification of chromosomes w During mitosis. This chromosome abnormality leads to programmed cell death in mitotic cells. Here we have shown that SB715992 cell death induced apoptosis significantly PC 3 prostate cancer cells [Read the Full Post]

EGFR INHIBITORS AGAINST THE CANCERS

4300 | Sep 12 2012

INHIBITION OF EGFR: Among those few cascades which play an important role in the functioning of cells, epidermal growth factor receptor or EGFR pathway is one that has a vital role in growth, survival and proliferation of cells. The importance of this cascade can only be observed and understood in case of development of tumors and fatal diseases related to the uncontrolled cell growth caused by the improper regulation of EGFR signaling pathway. Over or mutated expression of the EGFR is associated with different types of cancers like colon, lung and breast cancers and with multiform glioblastoma, anal and epithelial cancers. Therefore the treatment of these cancers by using the phenomenon of EGFR inhibition is found to be an attractive approach that led to magnify the importance of Erbb1 inhibitor. These inhibitors along with their use in clinical processes, are also concerned with the survival of patients and different EGFR antagonists and agonists are also in use for the revelation of various other cascades and the effects of EGFR pathway on them. EGFR inhibitors can be obtained from any relevant supplier at a very normal cost. [Read the Full Post]

PAZOPANIB: LATEST VEGFR INHIBITOR

3240 | Sep 11 2012

PAZOPANIB: A very famous pharmaceutical company named GlaxoSmithKline is the manufacturer of a very important anticancer drug Pazopanib Votrient also called Pazopanib VEGFR inhibitor and is selling it by the market name Votrient. Pazopanib is a quick source of anti-angiogenic activity that inhibits VEGF, R1, VEGFR2 and VEGFR3 in conjunction with the β subtypes and c-kit RTKs and PDGFR-a. Pazopanib is such a tiny structure that got fame only in previous years by showing its remarkable activity in various sorts of cancers. Pazopanib VEGFR-PDGFR inhibitor is indeed one amongst those necessary inhibitors that are currently approved for the utilization at clinical level [1]. Pazopanib structure reveals the presence of a sulfonamide group. One can purchase Pazopanib from supplier Pazopanib by paying Pazopanib price that is around $100 per a 25mg packing under the market name Votrient or GW786034. Its price might vary among the suppliers. Pazopanib solubility is ideally detected in DMSO however it is fully insoluble in water and ethanol. It is stability is increased for nearly 2 years if preserved at -20oC. The studies revealed that Pazopanib IC50 value for VEGF-R1 is 10nM, for VEGF-R2 is 30nM and for VEGF-R3 is 47 nM. Pazopanib IC50 values for few related kinases for example PDFGR-beta is 82 nM, c-fms is 146 nM, c-kit is 74 nM and FGFR1 is 140 nM. [Read the Full Post]

ERLOTINIB– INHIBITOR OF EGFR

517 | Sep 03 2012

CHARACTERISTICS OF ERLOTINIB Erlotinib is one of the tyrosine kinase inhibitors which is also referred OSI-420 EGFR inhibitor which is typically named as HCl salt. Epidermal growth factor tyrosine kinase receptor is sometimes seen abnormal in numerous kinds of cancers so that they are being utilized for the anti-cancer therapy. Plenty of new medicines are being created by using a similar approach [1]. Erlotinib structure revealed that it contained 2 quinazoline rings in its structures and it showed to inhibit the EGFR auto phosphorylation which eventually stops the pathway that is involved in the overexpression of genes. Around 18mg/ml in dimethyl sulfoxide (DMSO) is the Erlotinib solubility however it is scarcely soluble in water and ethanol. For inhibition of EGFR 20nM is Erlotinib IC50 [2]. It is readily oxidized therefore care should be taken to extend its shelf life. Approximately $65 per 1000mg is Erlotinib price and any one can get OSI-420 for any kind of purpose under this trade name. [Read the Full Post]

SORAFENIB-AS A MULTIKINASE INHIBITOR

2361 | Aug 30 2012

SORAFENIB: INTRODUCTION For receiving extracellular or intracellular stimulus numerous types of non-receptor and receptor tyrosine kinases are present in cells which are capable of conducting inhibitory and initiatory action on different signalling pathways. Defect of any type in these processes can cause cancer. The kinases which are involved in the over-expression or under expression of gene that are cause of cancer can be used as target for cancer therapy. Different types of kinases are being inhibited by employing only one inhibitor. Due to the involvement of abnormal tyrosine kinase in the development of cancer inhibitors of tyrosine kinases are being developed and studied to use it as for the treatment of cancer. Clinical trials of different inhibitors have shown outstanding results. Among these inhibitors one important inhibitor is Sorafenib inhibitor which has shown to inhibit kinases excluding respective VEGFR. Similarly Raf pathway/ERK/MEK pathway have been found inhibited by the administration of Sorafenib Raf inhibitor. [Read the Full Post]

IGF-1R INHIBITOR IN CANCER TREATMENT

3525 | Aug 27 2012

SIGNALING CASCADE AND DEVELOPMENT OF CANCER: Insulin like growth factor 1 is one of the signaling molecules in the human cells abbreviated as IGF-I also known as somatomedin or sulfation factor. As the name indicates, the structure of the protein resembles insulin and is responsible for stimulating a signaling cascade via a transmembrane receptor protein i.e., IGF-1 receptor. This receptor is very important due to its role in the process of insulin signaling and aging. This preceptor has also been connected with different types of cancers e.g., prostate cancer, breast cancer and lung cancer. This receptor has been found to provide resistance to the cells against radiotherapy and chemotherapy and hence shows anti-apoptotic characteristics. One example of such resistance is that of Erlotinib, EGFR inhibitors which is used against breast cancer and inhibits EGFR signaling pathway but IGF1-R in these cells produces resistance against the drug. It has been reported to form heterodimers that tend the EGFR pathway to continue rather than inhibiting it. This relationship between IGF-R and EGFR has been studied in breast cancer and the development of metastasis or tumor invasion by angiogenesis was reported. Therefore, inhibiting IGF1-R can be a way to prevent lots of signaling cascades towards malignancies. [Read the Full Post]

CANCER TREATMENT BY c-MET INHIBITORS

3387 | Aug 26 2012

c-MET INHIBITION: APPLICATIONS IN CANCERS: A proto-oncogene encoding the hepatocyte growth factor receptor or HGF-R is known as c-Met, and its hyperactivation causes certain changes like angiogenesis or formation of the new blood vessels leading to the invasive growth of tumor. The aberrant regulation of Met has reported to the leading cause of many types of cancer like liver cancer, stomach cancer, breast cancer, ovarian cancer, thyroid cancer and brain cancers. Due to this particular property of c-Met gene, its inhibition process has become an attractive target for the therapeutic use. That’s why huge research is being made for the synthesis of antagonist of c-Met or simply am7 inhibitor having clinical and therapeutic implications. Along with this application, the c-Met agonists and antagonists are being utilized for understanding of different cellular cascades and throwing light on interactions of c-Met with other molecules. Many of these commercial c-Met inhibitors like bayer kinase inhibitors are easily available from their suppliers and one has an easy access to them. [Read the Full Post]

c-MET INHIBITORS IN CANCER TREATMENT

4538 | Aug 20 2012

c-MET AND ITS INHIBITION: c-Met is encoded by a proto-oncogene and is also known as HGF-R or hepatocyte growth factor receptor. As it is a proto-oncogene, therefore, its hyperactivation is involved in development of different cancers. c-Met is known to form new blood vessels in growing tumors and hence help their invasion to other tissues. Different examples of cancers involving c-Met aberrant behavior are stomach cancer, liver cancer, breast cancer, thyroid cancer, ovarian cancer and brain cancer. Because of involvement of this particular oncoprotein in many cancers, it has remained target in lots of research related to anti-cancer therapy. Lots of c-Met antagonists have been developed and one of the examples is c-Met inhibitors that has been implicated clinically and therapeutically. Different other antagonists and agonists of c-Met are also being used in order to get an understanding about different functions of c-Met and the types of interactions that it has with other molecules in the signaling cascade. Many of the c-Met inhibitors are commercially available at reasonable prices for example tyrosine kinase inhibitor. These inhibitors can be easily bought from the suppliers for any purpose. [Read the Full Post]

EGFR INHIBITORS IN CANCER THERAPY

4535 | Aug 17 2012

EGFR AND DEVELOPMENT OF CANCER: Among a variety of signal transduction pathways vital for cell survival, growth, and proliferation etc. EGFR pathway is considered to be quite important. Its importance has been judged by analyzing the processes like tumor development and some other diseases occurring due to uncontrolled growth of cells. Mostly EGFR signaling pathway malfunctioning has been linked with the development of such types of diseases in the body for example; colon cancer, breast and lung cancer and with anal cancer, multiform Glioblastoma and epithelial cancer. Therefore targeting EGFR for cancer therapy is a feasible approach. This EGFR inhibiting strategy magnifies the HER-1inhibitor and its importance. These inhibitors have a very significant role in the patients’ survival from the disease. Different EGFR agonists and antagonists are used for the purpose of unveiling the role of this molecule in the cell as well as looking for a most efficient EGFR inhibitor. These inhibitors are available at a very reasonable price and can be bought for any purpose. [Read the Full Post]

IGF-1R INHIBITOR IN CANCER TREATMENT

3938 | Aug 12 2012

SIGNALING PATHWAY AND CANCER: One of the important signaling molecules in body of human cells is the Insulin like growth factor 1 and abbreviated as IGF-I and also known as sulfation factor or somatomedin. Structure of this protein, as indicated by the name, resembles insulin and responsible of stimulating a signaling pathway through transmembrane receptor protein i.e., receptor IGF-1. The receptor is very much important for its role in process of aging and signaling of insulin. IGF-1 receptor is also connected to different types of tumors like breast cancer, lung cancer and prostate cancer. It was observed that this receptor offers resistance against chemotherapy and radiotherapy in the cells hence showing the anti-apoptotic activity. An important example of such resistance is Erlotinib, HER-1 inhibitors that is used against breast cancer and causes inhibition of EGFR signaling pathway but IGF1 receptor in cells generates resistance against this drug. The formation of hetrodimers has been reported that stimulate the EGFR cascade to further continue rather than its inhibition. [Read the Full Post]

IGF-1R INHIBITION AND CANCER TREATMENT

3363 | Aug 05 2012

SIGNALING IN CANCER: In humans a gene IGF-I encodes a protein known as insulin like growth factor 1 or abbreviated as IGF-1, this is also known as sulfation factor or Somatomedin. The name related to insulin is due to the structural similarities with insulin. This protein is responsible for the activation of a signaling pathway downstream to it and this is done by triggering IGF receptor known as IGF-1 receptor which is a transmembrane receptor. This receptor plays important roles in aging and insulin signaling but many reports are also there which have proven the connection of IGF1-R with many cancers for example prostate cancer, lung cancer and breast cancer as well. This receptor also provides resistance against chemotherapy and radiotherapy, hence showing anti-apoptotic characteristics. To this statement one example is of breast cancer where EGFR inhibitors such as Erlotinib are used for the EGFR signaling pathway checking but here IGF1-R produces resistance against Erlotinib by the formation of a heterodimer which tends the EGFR pathway continue regardless the presence of inhibitor. The link between EGFR and IGF-R is also noted in the breast cancer where angiogenesis resulted in the tumor invasion or metastasis. So, inhibition to IGF1-R is a way to abrogate many signaling pathways leading to malignancies. [Read the Full Post]

EGFR INHIBITORS AGAINST TUMORS

4137 | Jul 29 2012

EGFR INHIBITION: There are few pathways which play important roles in the cellular functioning and among these EGFR (epidermal growth factor receptor) pathway is one which is vital for the cell growth, proliferation and survival. The significance of this pathway can only be understood by the formation of cancers and fatal diseases associated with uncontrolled growth of cells due to dysregulation of EGFR signaling pathway. Mutated or over expression of EGFR is linked with many types of cancers for example breast, colon and lung cancers and also with glioblastoma multiform, epithelial and anal cancers. Therefore an attractive strategy to treat cancers was EGFR inhibition by using EGFR inhibitors. In addition to this use in clinics these are also involved in patient survival and various EGFR agonists and antagonists are also being used for the elucidation of different other pathways and effects of EGFR signaling pathway on them. These inhibitors are available at normal prices from any of the relevant supplier. [Read the Full Post]

c-MET INHIBITORS IN CANCER TREATMENT

2769 | Jul 26 2012

APPLICATION OF c-MET INHIBITION IN CANCERS: c-Met is a proto-oncogene which encodes HGF-R or hepatocyte growth factor receptor, hyperactivation of this gene activates certain changes such as formation of new blood vessels or angiogenesis which leads to invasive tumor growth. Met aberrant regulation reported to be a cause of many cancers such as stomach cancer, liver cancer, ovarian cancer, breast cancer, brain and thyroid cancers. Due to this characteristic of c-Met gene inhibition has become an attractive approach for therapeutic use. Therefore a huge research is being done for the development of c-Met antagonists or c-Met inhibitors which have therapeutic or clinical implications. In addition to this application c-Met antagonists or agonists are also being utilized for the understanding of various cellular pathways and imparting light on the interaction of other molecules with c-Met. Commercially many of these like kinase inhibitors are available from any of the suppliers and one can easily access to them. [Read the Full Post]

PAZOPANIB: INTRODUCTION

3627 | Jul 19 2012

PAZOPANIB: INTRODUCTION One of the very important anti-tumor drugs Pazopanib VEGFR inhibitor also known as Pazopanib Votrient is being produced by the very popular pharmaceutical company which is GlaxoSmithKline. It is selling this drug with commercial name of Votrient. Pazopanib inhibits the angiogenesis by blocking VEGF R1, R2 and R3 with their β subtypes and also inhibits c-kit RTKs as well as PDGFR-a. Though Pazopanib is tiny molecule yet it gains popularity due to its extensive potential on various kinds of malignancies. Pazopanib VEGFR-PDGFR inhibitor has now been approved to enter the clinical trials. It was revealed by the Pazopanib structure that it contained a sulfonamide group. It is marketed in 25mg of packaging with Pazopanib price of approximately $100 as Votrient or GW786034 and anyone can purchase Pazopanib for research or experimental purposes from supplier Pazopanib. Prices are being varied from supplier to supplier. Pazopanib solubility revealed it is best soluble in DMSO while it is absolutely insoluble in water and ethanol. Storing at -20oC shows stability for approximately 2 years. [Read the Full Post]

SUNITINIB-AN RTK INHIBITOR

3297 | Jul 17 2012

SUNITINIB: INHIBITS MULTIPLE KINASES There are different cell signaling processes in metabolic resources which supervise other important cellular functions. One of the most vital types of cellular processes is tyrosine kinase pathways which control many other important pathways like cellular proliferation, growth, apoptosis and cell survival etc. When these tyrosine kinases are over expressed the abnormal cell growth has been noted, which is the reason of many lethal diseases such as cancer. The approach of designing inhibitors for tyrosine kinases is one of the leading fields in drug designing against cancers. It is possible that a single inhibitor can inhibit the functions of multiple tyrosine kinases. One of the examples of cancer associated with tyrosine kinase is breast cancer where VEGF pathway gets abnormal. Many carcinomas has been handled by using inhibitors of tyrosine kinases [2] and one example is gastrointestinal stromal cancer where such inhibitors are being used and one another example is ALL (acute Lymphoblastic Leukemia) treatment. [Read the Full Post]

GEFITINIB; A POTENT INHIBITOR OF EGFR

606 | Jul 11 2012

INTRODUCTION AND MECHANISM OF ACTION There are many inhibitors of tyrosine kinase inhibitors and amongst these Gefitinib is one of the potent inhibitor. It gently inhibits the functions of EGFR or epidermal growth factor receptor. Currently there are two companies are producing Gefitinib including Astra Zeneca Company and Teva Company. Gefitinib Iressa performs its functions by inhibiting EGFR due to its structural properties which contains a ring structure of anilinoquinazoline. Gefitinib EGFR inhibitor costs around 80$ for a vial of 1g and it is available for anyone desired to purchase Gefitinib including researchers, scientists and for laboratory uses. Gefitinib is not soluble in water however Gefitinib solubility can be attained in ethanol, dimethyl sulfoxide (DMSO) and DMF. As far Gefitinib stability is concerned it is stable for a period of 2 years if stored at -20oC. Gefitinib IC50 is 37nM and 57nM for Tyr 1173 and Try 992 respectively. There were many assays were performed for the pharmacokinetics and sensitivity evaluation of Gefitinib. These assays were based on the information of some presumptive markers such as mutated forms of K-Ras and EGFR and variable copy number. Enzyme linked immunosorbent assay (ELISA) is carried out to analyze human serum and study of tissues against a specific drugs or HDRA. This is a competitor inhibitor of EGFR which competes with ATP and binds with ATP binding site present in EGFR which ultimately results in the inhibition of ligand binding and therefore inhibits the signal transduction which is caused by ligand binding. [Read the Full Post]

DASATINIB; An inhibitor of Receptor Tyrosine Kinase

9768 | Jul 04 2012

CHARACTERISTICS OF DASATINIB The amplified death rate because of cancer and multidrug resistance development in cancer cells for existing drugs are the persuasive force for the researchers as well as scientists to explore new drugs that have better efficiency. Each cellular system is organized by a diversity of controllers called cell cycle regulatory proteins.Cancer cells have the capability to mutate themselves in a variety of ways which make them to detour the action of a specific drug. Another concern with the cancer is that it metastasizes. Other difficulty with the chemotherapy of cancerous cells is toxicity. So considering afore mentioned problems it is evident and compulsory to search for new drugs. Due to above mentioned problematic effects of Imatinib which has been administered for years induces scientists to search for a more mild and more active drug. In this matter a new drug called Dasatinib was discovered by Jagabandhu Das. In contrast to Imatinib, Dasatinib BMS 354825 became renowned due to its lesser harmful and more efficient nature. This drug was discovered by Squibb Company and it is sold as Sprycel. [Read the Full Post]

SORAFENIB- A MULTIKINASE TYROSINE INHIBITOR

3150 | Jun 27 2012

SORAFENIB: INTRODUCTION Various kinds of non-receptor tyrosine kinases or receptor tyrosine kinases (RTKs) are available in the cells which are employed in responding to intra or extracellular stimulusby carrying out either initiatory or inhibitory action on various signaling pathways. Any sort of problem in this process may cause cancer. Inhibition of kinase enzymes to prevent some mal-expressed or over-expressed gene causing cancer is found to be an effective tool. Inhibition of various kinases is being done by using single inhibitor. Since malfunctioned tyrosine kinases are involved in onset of cancer, research is being done on their inhibitors for cancer therapy.Many of them are giving promising results in their clinical trials.An important example of these inhibiting drugs is Sorafenib VEGFR inhibitor that has been found to inhibit the protein kinases except respective VEGFR. When SorafenibRaf inhibitor was given Raf/MEK/ERK pathway was found inhibited. [Read the Full Post]

DASATINIB; A Receptor Tyrosine Kinase inhibitor

3906 | Jun 25 2012

PROPERTIES OF DASATINIB Researchers and scientists are trying hard to find a better drug with good efficiency because cancer has become the cause of huge deaths all over the world and secondly resistance to the available drugs in cancer cells is increased. Cancer cells evade the action of particular medicine to become resistant by mutating themselves in a number of ways. Metastasis is also another problem related to cancer. For chemotherapy of cancer cell toxicity adds to the problem. To combat these afore mentioned difficulties it is necessary as well as mandatory to devise new medicines. Imatinib was given for years but due to its toxicity and other effects mentioned above it forced scientists to develop a less toxic and more efficient medicine. So in this regard Jagabandhu Das developed a new medicine called Dasatinib. Dasatinib BMS 354825 got very popular as compared to Imatinib because of its lesser toxicity and more efficiency.It is developed by a pharmaceutical company Squibb and marketed under the trade name of Sprycel. [Read the Full Post]

ERLOTINIB– THE HCL SALT

4877 | Jun 19 2012

ERLOTINIB AND ITS PROPERTIES Erlotinib comes under the category of tyrosine kinase inhibitorswhich is also called OSI-420 EGFR inhibitor and usually named as HCl salt. Epidermal growth factor tyrosine kinase receptor is usually seen abnormal in various types of cancers so they are being employed for the anti-cancer therapy. A lot of new medicines are being produced by using the same approach [1]. Erlotinib structure revealed that it contained two quinazoline rings in its structures and it showed to inhibit the EGFR auto phosphorylationwhich eventually stops the pathway which is involved in the overexpression of genes. Around 18mg/ml in dimethyl sulfoxide (DMSO) is the Erlotinib solubility however it is scarcely soluble in water and ethanol. For inhibition of EGFR 20nM is Erlotinib IC50 [2]. It is easily oxidize able so care must be taken to increase its shelf life. Approximately $65 per 1000mg is Erlotinib price and buy OSI-420 for any kind of purpose under this trade name. [Read the Full Post]

SUNITINIB-AN INHIBITOR OF RECEPTOR TYROSINE KINASE

2819 | Jun 18 2012

A CHEMOTHERAPEUTIC AS MULTIKINASE INHIBITOR Tyrosine kinases are the enzymes which act as mediators between different cells to facilitate variety of metabolic processes in cells. Since these tyrosine kinases play important role in processes e.g. division, survival, multiplication, differentiation, growth and death of cell, their inhibition have been found very promising target. Any type of modulation of these enzymes can cause the downstream regulation of the pathways controlled by them. This behaviour is being exploited as inhibitors of tyrosine kinases for chemotherapy. Many tyrosine kinase inhibitors are multi kinase inhibitors as they can inhibit more than one type of tyrosine kinase enzymes. VEGF pathway involvement in breast carcinoma and some other tyrosine kinases in other cancers made these enzymes a popular interest. Different types of carcinomas are being successfully treated by using inhibitors of tyrosine kinase. [Read the Full Post]

SUNITINIB-AN RTK INHIBITOR

2944 | Jun 17 2012

MULTIKINASE INHIBITORS AND CHEMOTHERAPY A variety of cell signalling pathways are there in the cellular systems of the body that govern different cellular processes in the cells. Tyrosine kinase pathways are one of these pathways that play role in growth, proliferation, survival and apoptosis etc. Overexpressed tyrosine kinases may hence lead to cancer and is amongst the major reasons in most of the cancer conditions. Inhibition of tyrosine kinases is hence being done by using different types of tyrosine kinase inhibitors. A single inhibitor may sometimes block multiple kinases in one time. The examples of cancers involving tyrosine kinase defects is breast cancer in which VEGF pathway is disturbed. Various kinds of carcinomas involving such defects are being treated using these tyrosine kinase inhibitors for example gastrointestinal stromal tumors and Acute Lymphoblastic Leukaemia (ALL).  [Read the Full Post]

SORAFENIB-AS A MULTIKINASE INHIBITOR

3162 | Jun 08 2012

SORAFENIB For receiving extracellular or intracellular stimulus numerous types of non-receptor and receptor tyrosine kinases are present in cells which are capable of conducting inhibitory and initiatory action on different signalling pathways. Defect of any type in these processes can cause cancer. The kinases which are involved in the over-expression or under expression of gene that are cause of cancer can be used as target for cancer therapy. Different types of kinases are being inhibited by employing only one inhibitor. Due to the involvement of abnormal tyrosine kinase in the development of cancer inhibitors of tyrosine kinases are being developed and studied to use it as for the treatment of cancer. Clinical trials of different inhibitors have shown outstanding results. Among these inhibitors one important inhibitor is Sorafenib inhibitor which has shown to inhibit kinases excluding respective VEGFR. Similarly Raf pathway/ERK/MEK pathway have been found inhibited by the administration of Sorafenib Raf inhibitor. [Read the Full Post]

PAZOPANIB: LATEST VEGFR INHIBITOR

3372 | Jun 06 2012

PAZOPANIB: INTRODUCTION One of the very important anti-tumor drugs Pazopanib VEGFR inhibitor also known as Pazopanib Votrient is being produced by the very popular pharmaceutical company which is GlaxoSmithKline. It is selling this drug with commercial name of Votrient. Pazopanib inhibits the angiogenesis by blocking VEGF R1, R2 and R3 with their β subtypes and also inhibits c-kit RTKs as well as PDGFR-a. Though Pazopanib is tiny molecule yet it gains popularity due to its extensive potential on various kinds of malignancies. PazopanibVEGFR-PDGFR inhibitor has now been approved to enter the clinical trials. It was revealed by the Pazopanib structure that it contained a sulfonamide group. It is marketed in 25mg of packaging with Pazopanib price of approximately $100 as Votrient or GW786034 and anyone can buy Pazopanib for research or experimental purposes from supplier Pazopanib. Prices are being varied from supplier to supplier. Pazopanib solubility revealed it is best soluble in DMSO while it is absolutely insoluble in water and ethanol. [Read the Full Post]

SUNITINIB: THE MULTI-TARGETED APPROACH

2824 | May 31 2012

MUTIKINASE INHIBITORS IN CHEMOTHERAPEUTICS:  Different types of metabolic systems that occur between varieties of cells are mediated through a class of enzymes called tyrosine kinases. Since these tyrosine kinases play important role in processes e.g. division, survival, multiplication, differentiation, growth and death of cell, their inhibition have been found very promising target. By doing any change in them the processes which they regulate can also be down regulated. This behaviour is being exploited as inhibitors of tyrosine kinases for chemotherapy. The inhibitors of tyrosine kinases block multiple kinases at the same time. The involvement of tyrosine kinases in the pathways which cause different cancers like it is involved in vascular endothelial growth factor pathway in case of breast cancer and many other types of cancer makes them interesting. [Read the Full Post]

GEFITINIB; AN EGFR INHIBITOR

3980 | May 28 2012

PROPERTIES AND MODE OF ACTION Gefitinib is one of several tyrosine kinase inhibitors that are quite efficient in their activity. Gefitinib is actually an EGFR inhibitor. It is marketed by the two companies i.e., Teva and AstraZeneca. Gefitinib EGFR inhibitor is a strong inhibitory compound and Gefitinib structure shows the presence of a ring in it i.e., anilinoquinazoline. One can buy Gefitinib in the form of a 1 gm vial in approximately $80. Scientists can purchase Gefitinib for research or treatment purposes. Gefitinib solubility can be achieved in organic solvents like ethanol, DMSO and DMF and Gefitinib stability for approximately 2 years can be achieved if it is stored at -20 oC. Gefitinib IC50 for EGFR inhibition against Tyr 992 and Tyr 1173 is 37 nM and 57 nM respectively. Different types of assays have been designed to clinically analyze the pharmacokinetics and sensitivity of the drug. These assays are based upon some predicting markers e.g., EGFR mutated genes, copy number or K-Ras mutations. [Read the Full Post]

SUNITINIB: A MULTI-KINASE ENZYME INHIBITOR

3450 | May 24 2012

TYROSINE KINASE INHIBITORS Tyrosine kinase enzymes are very important amongst the diversified world of proteins involving the signal transduction process for their role in various processes like inhibition or activation of genes expression responsible for cell growth, cell division, cell differentiation and cell death. Abnormalities in these tyrosine kinases are leading cause of in the disruption in above mentioned functions stimulating the tumor development. The inhibition of tyrosine kinase enzyme is an attractive target when there is the disruption in any cell cycle regulatory enzyme affected by the tyrosine kinase in case of any kind of cancer. So these enzymes are the attractive target for anti-tumor drugs as they are those that start the function. Tyrosine kinase inhibitors are having the ability of affecting different kinds of tyrosine kinase enzymes hence called as multikinase inhibitors and they may be non-receptor or receptor kinases. If the type of kinase involving in the cancer condition is known, like for VEGF involved in the breast cancer, the medicine for choice must be a TKI. [Read the Full Post]

SUNITINIB: THE MULTI-TARGETED APPROACH

3243 | May 23 2012

MUTIKINASE INHIBITORS IN CHEMOTHERAPEUTICS: Tyrosine kinases are the enzymes which act as mediators between different cells to facilitate variety of metabolic processes in the cells. The inhibition of these enzymes is found to be a very attractive target due to their prime role in various important processes in the cells for instance cellular growth, survival, proliferation, apoptosis and differentiation. Any type of modulation of these enzymes can cause the downstream regulation of the pathways controlled by them. This is why inhibitors to tyrosine kinases are getting very famous as chemotherapeutic agents. Many tyrosine kinase inhibitors are multikinase inhibitors as they can inhibit more than one type of tyrosine kinase enzymes. VEGF pathway involvement in breast carcinoma and some other tyrosine kinases in other cancers made these enzymes a popular interest. Tyrosine kinase inhibitors are used successfully against solid form tumors and various multi tyrosine kinase inhibitors are used for treating gastrointestinal stromal tumors. Tyrosine kinase inhibitors are also employed for the treatment against acute form of lymphoblastic leukemia. [Read the Full Post]

PAZOPANIB: LATEST VEGFR INHIBITOR

3061 | May 22 2012

PAZOPANIB: INTRODUCTION A very famous pharmaceutical company named GlaxoSmithKline is the manufacturer of an important anticancer drug Pazopanib Votrient known as Pazopanib VEGFR inhibitor and is selling it under the trade name Votrient. Pazopanib is a good source of anti-angiogenic activity that inhibits VEGF, R1, VEGFR2 and VEGFR3 along with the β subtypes and c-kit RTKs and PDGFR-a. Pazopanib is a very small molecule that got fame in just in recent years by exhibiting its potential activity in case of different types of cancers. PazopanibVEGFR-PDGFR inhibitor is indeed one of those important inhibitors which are now approved for the use at clinical level [1]. Pazopanib structure reveals the presence of a sulfonamide group. One can buy Pazopanib from supplier Pazopanib by paying Pazopanib price that is around $100 per a 25 mg packing under the trade name Votrient or GW786034. Its price may vary among the suppliers. Pazopanib solubility is best observed in DMSO but it is completely insoluble in ethanol and water. It is stable for almost two years if stored at -20oC. [Read the Full Post]

SORAFENIB-AS A MULTIKINASE INHIBITOR

2843 | May 21 2012

SORAFENIB Various kinds of receptor and non-receptor kinase enzymes are there in the cells that are responsible of carrying out the signaling pathways of initiation or inhibition of cascades after getting intra or extracellular stimulus. Any sort of defect in this process may cause cancer. Inhibition of kinase enzymes to prevent some mal-expressed or over-expressed gene causing tumor is found to be an effective approach. Many multiple kinases can be inhibited by using a single inhibitor. Various types of inhibitors against these kinase proteins are being discovered and studied in order to develop some effective anti-cancer therapy, as many of the tyrosine kinase abnormalities used to become the cause of development of cancer. Many of them are giving promising results in their clinical trials. An important example of these inhibiting drugs is Sorafenib VEGFR inhibitor that has been found to inhibit the protein kinases except respective VEGFR. In the same way Sorafenib Raf inhibitor also an important drug used for the inhibition of MEK/ERK/Raf pathway. [Read the Full Post]

DASATINIB; AN ANTI-RTK DRUG

3940 | May 16 2012

DASATINIB AND ITS PROPERTIES The high rate of deaths due to cancer and the development of resistance in the cancerous cells for existing drugs are encouraging the scientists and researchers to look for more efficient drugs. Occurrence of different types of mutations makes the cancerous cells to evade the drugs’ action against them. Metastasis is another problem in cancer that complicates the issue. Toxicity is another that is raised in cancer chemotherapy, therefore considering all of the developing complexities, new drugs are quite necessary to be discovered and developed. In case of leukemia, Imatinib had been used since long but due to the complexities associated with this drug, as mentioned above, led the scientists to look for another less toxic and more efficient drug. Jagabandhu Das was the discoverer of a drug in this regards i.e., Dasatinib named so after its discoverer. Dasatinib BMS 354825 got very popular because of lesser toxicity and more efficacies as compared to that of imatinib. It was developed by the company Squibb and is sold under the name of Sprycel. [Read the Full Post]

PAZOPANIB – THE LATEST CLINICAL VEGFR INHIBITOR

2617 | May 10 2012

PAZOPANIB: INTRODUCTION Pazopanib VEGFR inhibitor is compound manufactured by a famous pharmacuetical company GlaxoSmithKline under the trading name of Votrient, is a potential source of anti-angiogenic activity which inhibits R1, VEGF, VEGF R3 and VEGF R2 along with β subtypes and PDGFR-a and c-kit RTKs. Pazopanib is a small molecule which got famous in recent years when it showed potential activity in various types of tumors. PazopanibVEGFR-PDGFR inhibitor is actually one of those few inhibitor molecules that are approved for their use at clinical levels. Its structure revealed the presence of sulfonamide group in it. One can purchase Pazopanib to supplier Pazopanib under the trading name Votrient or GW786034 by paying the price around $100 for a 25 mg vial. Pazopanib price may vary from supplier to supplier. Pazopanib solubility is very good in DMSO but not in water and ethanol. Its stability is for almost 2 years when stored at -20oC. Pazopanib IC50 for efficient VEGF R1, VEGF -2, VEGF -3 inhibitions is actually 10 nM, 30nM and 47 nM respectively. For closely related kinase enzymes for example PDGFR-FGF R1, c-Kit and c-fms, Pazopanib IC50 was recorded as 85 nM, 140 nM, 74 nM and 146 nM, respectively. [Read the Full Post]

GEFITINIB – EGFR REGULATING DRUG FOR LUNG CANCER

3731 | May 02 2012

GEFITINIB: PROPERTIES AND MECHANISM OF ACTION There are two companies that are marketing Gefitinib named AstraZeneca and Teva. Gefitinib drug is actually Gefitinib EGFR inhibitor molecule that is an efficient and strong compound and has undergone clinical trials. Gefitinib structure reveals that a ring of anilinoquinazoline is present in it. Gefitinib price for a 1 gram vial is around $80 and due to its reasonable price one can purchase Gefitinib EGFR inhibitor very easily for laboratory or research purposes from any supplier Gefitinib. Gefitinib stability is for almost 2 years if stored at -20 degrees. To inhibit Tyr 1173 and Tyr 992 properly, the Gefitinib IC50 is found to be 57 nM and 37 nM respectively for inhibition of EGFR. Various Gefitinib assays were carried out to check the sensitivity and pharmacokinetic properties of this drug and those clinical assays were found to base upon some certain predictive markers like EGFR mutated genes, mutations in K-Ras and copy number. [Read the Full Post]

ERLOTINIB (OSI-420) –A SALT OF HCL

3193 | May 01 2012

INTRODUCTION: Erlotinib drug is commonly known as HCl salt. It is also called as OSI-420 EGFR inhibitor. It is a small molecule of tyrosine kinase inhibitor that works against the receptor for epidermal growth factor. This epidermal growth factor results usually very high levels of expression and mostly gets mutated in case of various types of tumors, hence a valuable and attractive target for anti-tumor therapy. One can order OSI-420 to any of the supplier OSI-420. So one can purchase OSI-420 by paying Erlotinib price to its supplier that is around $65 for 1000 mg vial. Erlotinib structure describes that it has 2 rings of quinazoline. OSI-420 has found to be inhibiting the autophosphorylation of epidermal growth factor to render downstreaming of already stopped signaling cascade by binding to ATP binding site of EGFR in the reversible manner leading to a permanat change in its conformation or structure. Erlotinib solubility is 18 mg/ml in DMSO while it is very poorly soluble in water and ethanol. To inhibit EGFR tyrosine kinase enzyme in human, Erlotinib IC50 was found to be almost 20 nM. OSI-420 EGFR inhibitor must be kept far away from different oxidizing agents so that it will remain stable and safe. [Read the Full Post]

DASATINIB: A DOUBLE-EDGED SWORD

2677 | Apr 25 2012

The demand for advance and innovative therapeutic tools has always been in high level for the efficient treatment of various kinds of cancers. The cancers that are highly proliferative and metastatic in nature have put an additional stress on the designing and discovery of a medicine or drug which promises better results. Mostly they adapt such mutations which tend them to remain unaffected to further treatment as a result evading the effects of drugs targeting them. High level toxicity is another big problem related to chemotherapy. For the treatment of blood cancer, Imatanib is found to be the best example of above mentioned statement. The reason that lead to the discovery of a better, less toxic and an efficient drug for treating white blood cell cancer is actually the resistance developed against Imatinib in the leukemic cell lines and its higher level of toxicity. [Read the Full Post]

SORAFENIB-A MULTIKINASE INHIBITOR

2202 | Apr 24 2012

SORAFENB Different types of receptor or non-receptor kinases are there in the cells that are involved in the signaling process in order initiate or inhibit a process after getting extra/intracellular stimulus. Any defect in this system may lead to cancer. Inhibition of Kinases in order to prevent any over-expressed or mal-expressed gene causing cancer is a very effective strategy. There are multiple types of kinases which can be inhibited by a single type of inhibitor. As various Tyrosine kinase aberrations become the reason for developing cancers, many inhibitors against these proteins are being researched in search of developing an effective anti-cancer therapy. Any of them are undergoing clinical trials and are giving promising results. One of the examples of such inhibitors is Sorafenib VEGFR inhibitor that has also been seen to inhibit protein kinases other than respective VEGFR. Similarly Sorafenib Raf inhibitor may be used effectively for inhibition of MEK/Raf/ERK pathway. [Read the Full Post]

SUNITINIB- A MULTI-KINASE INHIBITOR

2113 | Apr 22 2012

TYROSINE KINASE INHIBITORS Amongst a diversified world of signal transduction proteins, Tyrosine kinase proteins are important due to their role in different processes like activation or inhibition of expression of genes involved in growth, cell division, differentiation and cell death. Aberrations in any of such tyrosine kinases may lead to disruption in any of the above mentioned function and may develop tumor. In any type of cancer where any of the cell cycle regulatory protein that is affected by tyrosine kinases is disturbed, inhibition of Tyrosine kinases may work well to cope with the condition. They are attractive targets for anti-cancer drugs as they are the ones that start the activity. TKIs (Tyrosine Kinase Inhibitors) may affect different types of Tyrosine kinases, therefore are called as multikinase inhibitors they may be receptor or non-receptor tyrosine kinases. If we know the type of kinase involved in the cancerous condition, e.g., if VEGF involved in breast cancer, the drug of choice is definitely a TKI. [Read the Full Post]

TYROSINE KINASE INHIBITORS

1762 | Apr 19 2012

TYROSINE KINASE INHIBITORS Amongst a diversified world of signal transduction proteins, Tyrosine kinase proteins are important due to their role in different processes like activation or inhibition of expression of genes involved in growth, cell division, differentiation and cell death. Aberrations in any of such tyrosine kinases may lead to disruption in any of the above mentioned function and may develop tumor. In any type of cancer where any of the cell cycle regulatory protein that is affected by tyrosine kinases is disturbed, inhibition of Tyrosine kinases may work well to cope with the condition. They are attractive targets for anti-cancer drugs as they are the ones that start the activity. TKIs (Tyrosine Kinase Inhibitors) may affect different types of Tyrosine kinases, therefore are called as multikinase inhibitors they may be receptor or non-receptor tyrosine kinases. [Read the Full Post]

DASATINIB- A MULTI ACTION INHIBITOR

2621 | Apr 15 2012

Cancer has always been an area of research that has got much attention due to its diversity in reasons and mechanisms and hence to look for the treatment. Metastasis is another challenge that has to be controlled over in order to get rid of this disease completely. Due to this diversity every single treatment does not necessarily suits every single cancer patient. Therefore it is need of the hour to discover and synthesize new and more effective drugs with lesser toxicity as occurs in different chemotherapeutic agents for example in case of leukemia, Imatinib is a very good example. Toxicity of Imatinib at high level led the scientists to discover a new drug named Dasatinib. Dasatinib BMS-354825 is comparatively efficient and is less toxic. It is sold under the trade name of Sprycel. Dasatinib has been named on the name of the inventor Jagabandhu Das and was developed by Squibb. [Read the Full Post]

GEFITINIB – EGFR REGULATOR IN LUNG CANCER

2971 | Apr 12 2012

PROPERTIES OF GEFITINIB AND MECHANISM OF ACTION: Teva and AstraZeneca are the manufacturing and marketing companies of Gefitinib. Gefitinib EGFR (HER) inhibitor is a strong and efficient compound that has undergone clinical evaluations. An anilinoquinazoline ring is present in the structure of Gefitinib. For a 1 gram package the price for Gefitinib is about $80 due to this reasonable cost its easier to buy Gefitinib. If someone wants to order Gefitinib for research or laboratory uses one can contact any of Gefitinib suppliers. It can be stable for 2 years if properly stored at -20 oC. For proper inhibition of Tyr992and Tyr1173 Gefitinib IC50 is 57nM and 37nM respectively for EGFR inhibition. Different Gefitinib assays are done to analyze the pharmacokinetics, sensitivity and effect of this agent and those assays were based on certain predictive markers such as EGFR mutated gene, K-Ras mutations and copy number. In routine researchers use HDRA (histoculture drug response assay) or ELISA (enzyme linked immunosorbent assay) of human serum in order to analyze its pharmacokinetics studies. The mechanism behind the actions of Gefitinib is the binding of this compound competitively with EGFR ATP-binding site in cancer cells surface hence resulting in the inhibition of EGFR tyrosine phosphorylation induced by ligand to check downstream pathways. [Read the Full Post]

LINIFANIB-A FIRST LINE INHIBITOR AGAINST CANCER

3717 | Apr 11 2012

RECEPTOR TYROSINE KINASES AND CANCER Receptor tyrosine kinases (RTKs) are transmembrane receptors that start signaling cascade inside the cell after getting stimulated by different types of respective ligands. The stimulation may arise from the immediate or far away surroundings of the cell. Actually they respond to the needs of their extracellular environment by stimulating or inhibiting different types of cellular activities of regulation of cell cycle e.g., expressing or inhibiting a gene. After getting stimulated they phosphorylate themselves, dimerize and initiate a signaling cascade in multiple dimensions showing amplified effect of a single ligand. As these receptors have multiple types of effects therefore any change in their structure might lead to a gross change in the activities and behavior of the cell. As they are cell cycle regulatory proteins there over or under expression may lead to different types of diseases like cancer. [Read the Full Post]

MASITINIB – A DIVERSIFIED TYROSINE KINASE INHIBITOR

2639 | Apr 10 2012

TYROSINE KINASES AND MASITINIB Different types of chemotherapeutic drugs are there that target different tyrosine kinase receptors due to their role in different types of cancers e.g., pancreatic and gastrointestinal tumors, different inflammatory conditions and other diseases. Major focus is being given to VEGF-R (Vascular endothelial growth factor receptor), PDGF-R (Platelet derived growth factors), FGF-R3 (Fibroblast growth factor receptor 3), c-Kit and FAKs (Focal adhesion kinases). These proto-oncogenes have different functions in the cells. PDGF-R function in the proliferation and survival of cell, FGF-R3 controls mitotic and differentiation processes. c-Kit, a cytokine receptor is expressed on mast cell surface and can be involved in germ cell tumors, GISTs (gastrointestinal stromal tumors) and leukemia etc. and FAKs contribute in metastasis. All of these TKs, therefore, provide an attractive target for anti cancer drugs. [Read the Full Post]

FINGOLIMOD – AN IMMUNOMODULATOR

2599 | Apr 02 2012

PROPERTIES AND ORIGIN: Fingolimod (FTY720) derivative of a metabolite of a fungal strain Isaria sinclairii,and is known to be the 1st oral medicine which recently get approval for using against the multiple Sclerosis. Multiple seclerosis is an auto immune disease hence Fingolimod offers a glimmering hope against this debilitating disease. Fingolimod got approval in 2010-11 and after its approval Novartis (manufacturers) ensured its continous availability in market for patients. structure of Fingolimod SIP receptor inhibitor is chemically very different from ISP-1 (parent metabolite) and in order to enhance its efficacy and phamacokinetic properties, this sphingosine analog molecule is rationally modified. This drug is marketed by name Fingolimod Gilenya. This drug is an immunomodulating one and was used as an anti-rejection drug after the transplantation processes in clinical trials of phase I and phase II. [Read the Full Post]

ERLOTINIB (OSI-420) – AN HCL SALT

3001 | Apr 02 2012

INTRODUCTION: Erlotinib is commonly known as Erlotinib salt of HCl. It is a very small tyrosine kinase inhibitor molecule, works against the epidermal growth factor receptor. This EGFR usually gives high level of expression and most often gets mutated in different types of cancers, hence an attractive target for the anti-cancer therapy. Researchers can purchase Erlotinib from supplier Erlotinib which sale it under the trading name of Tarceva. By paying Erlotinib prices around $65 for a 1000 mg vial one can buy OSI-420. Structure of Erlotinib reveals that it is having 2 rings of quinazoline. Erlotinib has found to inhibit the autophosphorylation of EGFR to render the downstreaming of stopped signaling pathway by binding to the ATP binding region of EGFR in a reversible manner causing a permanent conformational change in its structure. Erlotinib is poorly soluble in ethanol and water but gives a solution of 18 mg/ml upon heating in DMSO. For the inhibition of EGFR tyrosine kinase in human, Erlotinib IC50 is found to be near 20 nM. Erlotinib must be stored far away from oxidizing agents to keep it safe and stable. [Read the Full Post]

A DOUBLE-EDGED SWORD: DASATINIB

2505 | Mar 29 2012

For the proper treatment of different types of cancers, there has always been a great demand of new and innovative therapeutic options. Those cancers are mostly highly metastatic and proliferative , and this thing puts an additional stress upon the discovery or designing of a drug which gives promising results. They most often develop some mutations which make them unaffected to on-going treatment hence evading the effect of medicines which target them. High toxicity level is another major problem related to chemotherapeutics. Imatanib is one of the prominent examples of above described statement which was in use for the treatment of leukemia. The high level of toxicity and the resistance developed against Imatanib in leukemic cell lines has led to the discovery of another efficient and less toxic drug for treatment of WBC carcinoma. Dasatinib BMS-354825 is such a drug named after its inventor Jagabandhu Das. It enters the horizon of success at this stage hence found to be a good replacement therapeutic agent developed by Squibb for the treatment of cancer and is sold now under the name of brand Sprycel. [Read the Full Post]

LINIFANIB: INHIBITOR FOR RECEPTOR ENZYMES

2429 | Mar 28 2012

LINIFANIB: A MULTIPLE KINASE INHIBITIOR: Receptor tyrosine kinases are the enzymes which are responsible of receiving signals from neighboring cells and extracellular environment so they are mostly the initiating point for the different signaling pathways and hence known as sentry of cells. Due to their importance in different signaling cascades, even very small changes in the activity or structure of RTKs can get magnify in form of differential signaling and leads to an entirely different outcome. In various diseased conditions, especially cancers, different receptor tyrosine kinases are either dysregulated or over expressed and finally lead to target the very first signaling level, which is an attractive approach in anti-tumor therapeutics. Due to their broad spectrum of action, it’s testing and development is very much welcome. Linifanib is a small inhibitor molecule which targets more than one Receptor tyrosine kinase enzymes. The potential anti-cancer property of Linifanib PDGFR inhibitor was discovered when its tumor regression in xenografts of human fibrosarcoma cells HT1080 and in estradiol-induced uterine edema’s model of murine. Synthesis of Linifanib took place as a side product of chemical modification in certain drugs. [Read the Full Post]

PAZOPANIB – A NOVEL VEGFR INHIBITOR FOR CANCER TREATMENT

2217 | Mar 27 2012

PAZOPANIB INTRODUCTION: Pazopanib is a product of GlaxoSmithKilne (GSK) pharmaceutical company and is traded under the name of Votrient, it is an anti-angiogenic chemical compound. Pazopanib VEGFR-PDGFR inhibitor which acts on multiple VEGFR (R1, R2 and R3) and it is also a potent inhibitor of PDGFR’s α and β subtypes and RTK c-kit receptor is also found to be inhibited by Pazopanib. In recent years great potency of this compound has been reported against different tumors and these findings brought fame to this molecule. It is amongst few VEGFR inhibitors which are approved for clinical usage. The structure of Pazopanib contains a sulfonamide group. The Pazopanib price for a vial of 25mg is about $100 but it variability is found from one Pazopanib supplier to other. If someone wants to purchase Pazopanib one can buy Pazopanib by trade name Votrient or GW786034. This compound is soluble in the DMSO and it is stable for atleast two years when stored at -20oC. IC50 for its effective response is 10nM, 30nM and 47 nM for VEGFR1, R2 and R3 respectively. And IC50 for PDGFR-beta FGF R1, c-fims and c-Kit is 84nM, 140nM, 74nM, 146 nM and 140nM respectively. [Read the Full Post]

BOSUTINIB- SRC INHIBITOR

2839 | Mar 26 2012

BOSUTINIB AND SRAC INHIBITORS Although the RTKs are found to be very important and valuable molecules due to their role in signaling pathways, some other non RTKs (receptor tyrosine kinases) are also being found to play a key role in regulating the down stream signaling. An important example is SRC kinases family which phosphorylates the tyrosine residues of many membranes, nuclear and cytosolic proteins hence regulating the signaling pathways. Foe their property of making interconnections, SRC kinases is proved to be an attractive target for many inhibitor molecules for these signaling pathways and chemotherapy. Bosutinib SRC inhibitor, an example of such molecules which target not only SRC family kinases but also up regulate the ABL kinases, hence have a broad spectrum activity. [Read the Full Post]

NERATINIB – THE DUAL INHIBITOR

3657 | Mar 19 2012

Introduction: The HER family of proteins Epithelial growth factor is a common term in the field of biology, but what is not specificed is that this protein is a member of larger group of four protein with similar mechanisms and structures. This family is called the HER series of proteins and are labeled logically as HER 1-4. Illogically this proteins are still referred to under their old names such EGFR (HER 1) or ErRB 2-4 (HER 2-4) in many articles in literature. These proteins function as a signaling mechanism across the cell membrane and they achieve this by having a receptor domain on the cell membrane exterior surface (head) connected to binding domains in the cytosole (tail). Binding of extracellular ligands to the “head” starts a chain reaction of events the first of which is the dimerization of the protein with another HER receptor. This caused structural changes transmitted through the “body” of the protein into the tail where Tyrosine binding domains are revealed. Kinase action will phosphorylate these domains activating them to binding of cytosolic ligands. Subsequently protein interaction transmits the signal from the original extracellular receptor all the way to the nucleus to initiate actions. [Read the Full Post]

GEFITINIB – REFGULATING EGFR in CANCER

2900 | Mar 19 2012

Introduction: The HER (EGFR) pathway and Gefitinib Protein kinases have been established in recent years as prime targets for selective inhibition in many disorders involving cell proliferation or cell migration. The extent of the protein kinase system is very large with hundreds of different proteins interacting together to send multitude of signals to nuclei determining growth, death, transcription or response to any form damage or stress. To enable understanding of the mechanism of action for all these proteins they have been classified under pathways which are directly related. One of these pathways that is significant in its effects is the HER pathway, originally known as the EGFR pathway in relation to the epithelial growth factor. However, more proteins related to EGFR were recognized (ErRB 2-4) and the HER family was born. The location of this series of proteins is too span across the cell membrane from the extracellular region (head) into the cytosole (tail). Attachment of ligands to the extracellular sites cause structural changes to the protein which expose tyrosine kinase binding domains in the section of the protein located in the cytosole. [Read the Full Post]

ERLOTINIB – A ONE STOP SHOP

2775 | Mar 19 2012

Introduction: The HER (EGFR) pathway and Erlotinib Extracellular and intercellular signaling is a major process in the regulation of the life and death of cells within in any tissue matrix. One of the most well known and significant of these signaling steams is the HER protein family pathway consisting of four distinct receptors. Originally this was solely recognized as HER1 receptor called, due to its ligand association and since it was primarily found in epithelial cells, the “epithelial growth factor receptor”. Abbreviated to the acronym EGFR this receptor has since been found to have a family of 3 other closely related protein receptors, HER 2-4. Unfortunately these were known as ErB2-4 before the relationship with EGFR was determined, since then the entire family has been renamed to the HER family. These receptors consist of an extracellular section (head) with a Trans-membrane section and a cytosolic section (tail). Ligands binding to the extracellular domains initiate a dimerization between receptors which in turn induce conformational changes. [Read the Full Post]

EGFR INHIBITORS VERSUS CANCER

2882 | Mar 20 2012

Introduction: The HER family of proteins Recently collated and renamed as a single family of homologous series of proteins the HER family represents a major group of cellular membrane signal transmitters. Confusingly in literature the new naming system is inconsistently followed and the four HER receptors are often referred to as EGFR (HER1; ErRB1), ErRB2 (HER2), ErRB3 (HER3) and ErRB4 (HER4). These receptors have a very specific mode of action in that extracellular ligands can bind to the surface receptor domains on the cell membrane. Binding to any one of four different versions the ligand can stimulate a number of possible responses. Upon binding, the complex formed will alter conformationally and dimerize with another HER receptor increasing the number of permutations possible in the signaling process. The Dimerization initiates changes in the conformational state of the protein that induces the intercellular segment of the protein to reveal binding domains previously hidden. The protein will auto-phosphorylate activating it to receiving intercellular protein binding which starts the signaling process with the cell. The number of pathways that can be activated in different ways is large leading to contradictory responses. [Read the Full Post]

LINIFANIB AGAINST RECEPTOR ENZYMES

2034 | Mar 20 2012

Introduction: Small molecule multi-kinase receptors The initiation of signaling cascades in most normal and tumor cell lines begin with the protein receptors on the surface of the cell membrane. Triggering a receptor by extracellular ligands induce dimerization and conformational changes in the trans membrane sub units of the receptor proteins. Such changes reveal tyrosine kinase binding domain within the cytosolic protein segments. Auto-phosphorylation activates the tyrosine kinase which in turn attracts proteins to complex. Phosphorylation of the tyrosine kinase binding domains of the complexed protein triggers release and the signal movement from membrane to cytosole. It his way further downstream targets are attracted, phosphorylated and released passing the signal to specific areas within the cell. The pathway ends when a cellular function such growth, differentiation and proliferation is induced. The two cell membrane receptors VEGFR and PDGFR are two of the most documented proteins. Inhibition of either of these two targets can induce various tumor reduction effects and apoptotic affects. [Read the Full Post]

PF-02341066 – A DUAL c-MET/ALK INHIBITOR

2985 | Mar 20 2012

Introduction: Either ALk or MET The inhibition of the transmembrane protein cMET demonstrated some notable success in the treatment of various different metabolic disorders. However, one of the key points which leads potent molecule to fail the phase I and II testing in reference to the mammalian system is the often extreme toxicity observed. A potent inhibitor that failed screening in this fashioned was PHA-665752, but structural studies with this molecule showed a binding conformation in the ATP domain of the tyrosine kinase section of the protein that could be adapted to different molecular structures. Utilizing this information a series of structurally related molecules were derived and screened for activity against cMET. In this way the PF-02341066 c-Met inhibitor was discovered and animal testing demonstrated anti-tumor activity. Closer investigations into the new molecule revealed that not only cMET was being inhibited but PF-02341066 also had activity towards ALK. [Read the Full Post]

SB-431542 – MEDIATES ALK INHIBITION

4548 | Mar 20 2012

ALK (ANAPLASTIC LYMPHOMA KINASE) RECEPTOR: Anaplastic lymphoma kinase or ALK is encoded by ALK gene and it is also called as CD246 (Cluster of Differentiation-246). This kinase is famous for the brain development but by the genetic fusion of any other gene it can be an oncogenic gene, another reason for its genetic variability is due to the normally found mutations of DNA. In case of ALCLs or large cell lymphomas, NPM (nucleophosmin) is present in fusion form with ALK and this is responsible for the 60% of this cancer. In some of the other cancers like NSCLC (non-small cell lung cancer) and most of adenocarcinomas, the ALK-EML4 fused genes are found as the main cause of tumor formation. Similarly in a pediatric cancer that is known as neuroblastoma, mutated ALK is reported as the main reason in various studies. All of these important examples enlighten the significance of this pathway in different cancers and tumors therefore the discovery or development of such compounds which inhibit the ALK TKs pathway is important. Certain approved inhibitors like Crizotinib used for lung cancer treatment enhances the uses of different inhibitors found in inhibitor library including SB-431542 ALK inhibitor. [Read the Full Post]

XL880 ; A BROAD SPECTRUM KINASE INHIBITOR

2763 | Mar 20 2012

XL880 AND THE INFERENCE OF INHIBITION OF VEGF-R/ MET/KDRIN TUMORS Many types of cancers exhibit the over expression of Met receptor tyrosine kinase or MTK, kinase domain receptors or KDRs contributing to tumor progression and hepatocyte growth factor or HGF (ligand of MTK). These KDRs are in fact is similar to interacting protein of MTKs, which is vascular endothelial growth factor or VEGF receptors. So the use of an inhibitor molecule which can inhibit these receptors can be a very valuable and attractive approach to treat cancers. XL880 MET inhibitor exhibits the same role. Another descriptive name for The XL880 VEGFR inhibitor is a EXEL-2880 (due to its discovery by the company named Exelixis) or Foretinib or GSK089 or GSK1363089 (now GlaxoSmithKline is also producing XL880 KDR inhibitor). XL880 structure reveals that it is a derivative of dicarboxamide. XL880 prices are not very low. Anyone can buy XL880 vial of 10 mg by paying $250 to XL880 suppliers. In DMSO XL880 solubility can be achieved while XL880 stability is around 2 years if stored at or below -20oC. To achieve an effective KDR and MET inhibition, XL880 IC50 is 0.8 nM and 0.4 nM respectively. [Read the Full Post]

SUNITINIB: THE MULTI-TARGETED APPROACH

0 | Mar 20 2012

MUTIKINASE INHIBITORS AS CHEMOTHERAPEUTICS: Tyrosine kinases are the enzymes which act as mediators between different cells to facilitate variety of metabolic processes in the cells. The inhibition of these enzymes is found to be a very attractive target due to their prime role in various important processes in the cells for instance cellular growth, survival, proliferation, apoptosis and differentiation. Any type of modulation of these enzymes can cause the downstream regulation of the pathways controlled by them. This is why inhibitors to tyrosine kinases are getting very famous as chemotherapeutic agents. Many tyrosine kinase inhibitors are multikinase inhibitors as they can inhibit more than one type of tyrosine kinase enzymes. VEGF pathway involvement in breast carcinoma and some other tyrosine kinases in other cancers made these enzymes a popular interest. Tyrosine kinase inhibitors are used successfully against solid form tumors and various multi tyrosine kinase inhibitors are used for treating gastrointestinal stromal tumors. Tyrosine kinase inhibitors are also employed for the treatment against acute form of lymphoblastic lekukemia. [Read the Full Post]

SORAFENIB: THE MULTIKINASE INHIBITOR

0 | Mar 20 2012

INTRODUCTION: By using multi-kinase inhibitors, more than one kinase enzyme at a time can be targeted so their use is considered to be very important and practicable approach for the treatment of cancers. Hence the use of a single inhibitor molecule having pan-tyrosine kinase ability is very attractive to target different overexpressed tyrosine kinases simultaneously. A lot of such inhibitor molecules are being used for this purpose which is showing very promising results in clinical trials. The property of Sorafenib VEGFR inhibitor is that it targets many other receptor molecules other than VEGFR. Sorafenib B-RAF inhibitor inhibits different pathways like Raf/MEK/ERK very efficiently which approves it’s as a multi-kinase inhibitor. [Read the Full Post]

MOTESANIB IN MULTIPLE ROLES

2180 | Mar 19 2012

Introduction: Multi-pathway inhibition One aspect of kinase inhibition that has become apparent during the testing of various small molecule inhibitors is that single agent therapy is only applicable in a small segment of the patients being treated. Different molecules inhibiting similar areas of the same pathway can have a different effect on which section of the patient population will respond. Combinations of single agents which have one main target kinase have demonstrated a greater efficacy when compared to the profile of the single agent alone. Hence the conclusion drawn from this is that multiple kinase inhibition is the more effective treatment path to follow. The subsequent development of multi-kinase inhibitors was triggered by the difficulty in combining single target molecules in a treatment profile. Treatment schedules were different, doses were different, toxicity was increased due to two or more drug treats rather than just the one and patient variability meant that a generalized schedule of treatment was a difficult compromise. Therefore, small molecules which targeted different pathways with a similar IC50 such as Sorafenib and Pazopanib are being intensely sort after. [Read the Full Post]

PAZOPANIB – THE LATEST VEGFR INHIBITOR IN CLINICS

2916 | Mar 19 2012

Introduction: The VEGFR pathway The VEGF pathway is the mechanism by which a mammalian system regulates the growth of vascular structures, such as blood vessels and lymphatic vessels. There exists three iso-forms of VEGFR spread across the cellular membrane of mostly endothelial cells, with a head in the extracellular medium and a tail in the cytosole. Ligand activity dimerizes the receptor and causes conformational changes to be transferred down the protein structure into the tail section where tyrosine kinase binding domains are revealed. There exists seven know ligands for the VEGF receptors known simple as VEGF-A, B, C, D, E, F or G. VEGF-A binds only to VEGFR 1 or 2 and it is reported that this is predominately regulates the formation and maintenance of the vascular system. VEGFR1 doesn’t appear to have a direct function of cellular response but has been suggested that it regulates VEGFR2 activity. VEGFR3 is less well known and only discovered recently, it appears to bind only to VEGF-C or D regulating the lymphatic system. Inhibition of the VEGFR focuses mainly on the isoforms VEGFR2 since this receptor is 90% responsible for all activity in this pathway. Pazopanib is a small molecule that inhibits all VEGFR isoforms and has demonstrated anti-tumor activity. [Read the Full Post]

ABT-869 – THE MULTI KINASE INHIBITOR

2673 | Mar 13 2012

ABT-869 – Tyrosine Kinase Inhibition: Tyrosine kinase is a family of enzymes that utilize phosphorylation of proteins to determine activity of many cellular functions. Tyrosine kinases are a sub family of the protein kinases which phosphorylate serine and threonine for cellular control. Mutation at the genetic level has been observed in this family of enzymes, which leads to the enzyme becoming unregulated. This over expression is observed in many cancer cell lines and represents a target for chemotherapy treatment. Tyrosine kinase inhibitors are novel small molecules which have come to the forefront of cancer research in recent times. Based on the designed molecule Imatinib, TKI’s have been developed to inhibit a wide range of tyrosine kinase receptor either as a single targeted or as a multiple targeted drug. ABT-869 PDGFR inhibitor, marketed under the trade name Linifanib, is a multi-targeted inhibitor against PDGFR-β, KDR, CSF-1R, FLT1, FLT4, KIT, FLT3 and Tie2. [Read the Full Post]

AMG706 – Multi targeted broad spectrum inhibitor

2729 | Mar 13 2012

AMG706: MULTI KINASE INHIBITOR Tyrosine kinases are a family of enzymes which fuction as regulators of many cellular processes but the phosphorylation of proteins. This process involves the action of ATP, the kinase and the target protein complexing for the transfer via a ATP binding domain on the tyrosine kinase. Computer simulation of the conformational structure of tyrosine kinases led to the development of a highly specific molecule which inhibited the phosphorylation by preferentially binding to the receptor domain. This molecule was determined to be very successful clinically in the treatment of chronic myelogenous leukemia (CML), gastrointestinal stromal tumors (GISTs). Imatinib is single kinase inhibitor but market driven forces have developed many tyrosine kinase inhibitors that either target single kinases or multiple kinases. [Read the Full Post]

SORAFENIB: THE MULTIKINASE INHIBITOR

3115 | Mar 13 2012

SORAFENIB INTRODUCTION: Sorafenib is a member of the class of compounds referred to as tyrosine kinase inhibitors. Developed originally as a Raf inhibitor the Sorafenib RAF inhibitor proved to be effective against more than one tyrosine kinase. Sorafenib demonstrated abilities to inhibit both tumor progression kinases and tumor angiogenesis kinases. As a direct result of the multiple targeting of this compound the Sorafenib PDGFR inhibitor has demonstrated activity in a wide range of cancer types such as renal cell carcinoma, breast cancer, hepatocellular carcinoma and colorectal carcinoma. Sorafenib is currently one of only 10 tyrosine kinase inhibitors approved for clinical use under FDA rulings (2005 – advanced renal cell carcinoma, RCC; 2007 – in inoperable Hepatocellular carcinoma, HCC), in addition Sorafenib has been approved by the European Medicines agency for use in HCC and RCC where first line therapy has failed. [Read the Full Post]

SUNITINIB: THE MULTI-TARGETED APPROACH

3379 | Mar 13 2012

SUNITINIB: A Multikinase Inhibitor Sunitinib is an oral, small molecule of the protein kinase subfamily called Tyrosine Kinase’s (TKI’s). Tyrosine kinases functions by the phosphorylation of a target protein utilizing ATP as its source. Phosphorylation of the target protein simulates either “on” or “off” in terms of activity. Unregulated activities of tyrosine kinases have been linked to many cancer types, leading researchers to develop strategies to inhibit specific Tyrosine kinase activity. TKI’s began to to be developed and tested pre-clinically in the late 1990’s and early 2000, several have reached fast track approval status due to the success of early trials. Sunitinib is one of the currently approved drugs and is approved for renal cell carcinoma (RCC) and imatinib-resistant gastrointestinal stromal tumor (GIST) as early as 2006. Sunitinib is the only TKI that has been approved for two different indications. [Read the Full Post]

Axitinib – A novel tyrosine kinase inhibitor

3898 | Mar 13 2012

Introduction Axitinib (AG-013736) is a small molecule 2nd generation inhibitor of tyrosine kinases (TKI). The unique aspect of this type of inhibitor is that they are orally administered yet remain a selective inhibitor of tyrosine kinases. Axitinib is a multi targeted inhibitor focusing on vascular endothelial growth factor receptors 1, 2 and 3 (VEGFR-1,2 or3), platelet derived growth factor receptor (PDGFR), and cKIT (CD117). VEGF is a functional part of the angiogenesis and vasculogenesis pathways and is frequently observed to be over expressed in various oncological conditions but not in normal tissue. Targeting molecules to inhibit tyrosine kinases represents a new novel approach to chemotherapy and over 50 such molecules have been developed for clinical use, 10 of which have been approved for clincal use. Axitinib is a pyrimidine core structure based on the first generation drug Imatinib., Imatinib was the first TKI to be approved for clinical use, it is used in the treatment of chronic myelogenous leukemia (CML) and gastrointestinal stromal tumors (GIST). Axitinib is still under development by Pfizer inc, originally called AG013736 it is currently undergoing several phase 1 and phase 2 trial in renal carcinoma. [Read the Full Post]

ANGIOGENESIS INHIBITORS TACKLING VASCULARIZATION

3856 | Mar 13 2012

THERAPIES AGAINST ANGIOGENESIS: During normal cellular growth patterns new blood vessels are formed to provide a vascular network to enable nutrients and oxygen enter and for waste to leave the system. This process is referred to as Angiogenesis. Tumors are unregulated cellular growths but they still require oxygen and nutrients to be able to grow, depriving tumors of either oxygen or nutrients would halt tumor growth or trigger tumor reduction through apoptosis. Since tumors are unregulated growth they require a more efficient or extensive vascular system than normal tissues hence angiogenic processes represent a possible chemotherapeutic target with angiogenesis selective inhibitors. Research has demonstrated over twenty different factors that regulate angiogenic processes providing a rich source of potential targets for angiogenesis pathway inhibitors. These all angiogenesis antagonists and either directly or indirectly affect the angiogenic processes. Angiogenesis inhibition takes advantage of known factors to develop precisely-structured proteins with known biological effects. Angiogenesis inhibitor drugs. can consist of small molecules such Marimastat or modified proteins such Bevacizumab. [Read the Full Post]

SKI-606 AGAINST SRC KINASES

3589 | Mar 13 2012

SKI-606: SRC Inhibitors Tyrosine kinases are a subgroup of the protein kinase super family and have been shown to regulate cell growth pattern, cellular proliferation, angiogenesis, invasion and metastasis in mammalian tissues. Many tyrosine kinases are up-regulated in tumor progression and present potential targets for chemotherapeutic inhibition. The Src kinase is non-receptor tyrosine kinase that includes 3 sub-families (SrcA,SrcB and SrcC). SrcA sub family is made up of Src, Yes, Fyn, and Fgr proteins while SrcB is made Lck, Hckm Blk and Lyn proteins. It has been reported in several tumor types that Src levels are elevated and this rise continues with progression of the disease. Tne mechanism behind Src elevation is not clearly understood and it is theorized that is the product of a “multifactorial process”. To further confuse the issue Src appears to changes its activity based on a direct or indirect interaction with EGFR, PDGFR, FGFR, CSF-1R, HER2 or c-MET. [Read the Full Post]

SB-431542 – MEDIATING ALK INHIBITION IN TUMORS

4911 | Mar 13 2012

Introduction: Inhibitors of ALK Activin receptor like-kinases (ALK1) are defined as being a type 1 receptor specifically for the transforming growth factor ß (TGF-ß) family of proteins. It is recorded that ALK1 expression is found in blood vessels and may be linked to vascular formation. Since tumor growth is dependant on generating a vascular skeleton to support itself ALK1 appears to be a potential target for chemotherapeutic action. Analysis of hereditary hemorrhagic telangiectasia disorders revealed a mutation n the ALK1 gene transcription. ALK is encoded by ALK gene and plays an important role in the development of brain function. Fusion of the ALK gene with other genes such as the nucleophosmin gene or the EML4 gene is can be linked to specifc types of carcinomas. In NSCLC the EML4- ALK fusion is theroised to be the driving force behind the tumor. Inhibition of the ALK, therefore presents itself forward a potential target for chemotherapy. This is confirmed by the EML4-ALK inhibitor Crizotinib which has achieved approval for use in NSCLC patients. Potentially SB-431542 is another small molecule which could make a huge impact since the SB-431542 IC50 has been determined to be 94nM for ALK5, it remains to be determined whether this can be translated into a sucessfuly chemotherapy agent. [Read the Full Post]

AV-951 – THE ANTI-ANGIOGENIC DRUG

2895 | Mar 13 2012

AV-951: Introduction Angiogenesis is the natural biological system for the formation of vascular networks, tumor growth requires materials and energy to grow, a vascular system therefore develops to supply the growing tumor with oxygen and molecules required for cellular construction. Factors affecting angiogenesis include transforming growth factors (TGF-beta), angiogenin, vascular endothelial growth factor (VEGF), fibroblast growth factors (FGF), epidermal growth factor (EGF) as well as TGF-beta and TNF-alpha which either directly or indirectly affect angiogenic processes. The development of small molecule anti- angiogenesis compounds has been reported extensively in literature. Of which the potent AV-951 VEGFR inhibitor, (a multiple tyrosine kinase inhibitor) has been shown to inhibit VEGF receptors 1,2 and 3 as well as c-KIT and PDGFR. AV-951 PDGFR inhibitor is an oral inhibitor given once daily that has demonstrated great potential in renal carcinomas at phase 1, 2 and 3 levels. It is also being investigated in a variety of other tumor types. [Read the Full Post]

EGFR INHIBITORS CONTROLLING TUMORIGENESIS

3550 | Mar 13 2012

Introduction: The EGFR’s role in the HER pathway A major pathway in the regulation of cell growth / death is the HER pathway, this pathway consists of four structurally related proteins primarily located in the cell membrane. The family members consist of HER1 (also known as EGFR), HER2 (also known as ErbB2), HER3 (also known as ErbB3) and HER4 (also known as ErbB4). These receptors consist of an extracellular head and an intracellular tail lying across the cell membrane. Ligands binding to the extracellular receptor induce conformational changes which reveal binding domains within the intracellular tail. Auto-phosphorylation of the tyrosine kinase domain is a result of the HER receptor forming dimers and depending on which of several different ligands induced the change the tail section attracts proteins to initiate signaling cascades to the nucleus. Ligands that trigger this signaling pathway consist of endothelial growth factor (EGF), transforming growth factor alpha (TGFα), beracellulin (BTC), epiregulin (EPR) and amphiregulin (AREG). [Read the Full Post]

XL880 AS MULTIKINASE INHIBITOR

2755 | Mar 13 2012

XL880: Inhibition of the VEGF-R/KDR/MET pathway Vascular endothelial growth factor (VEGF) is a signaling protein that is involved in the angiogenesis and vasculogenesis of damaged tissues. Increases in vascular structure are an important part of tumor growth and VEGF is often over-expressed in many forms of cancer. The mechanism of action of VEGF is through binding to the extracellular portion of the transmembrane VEGF receptors which leads to intracellular signaling which control stimulation of endothelial cell mitogenesis, cell migration, increases in  vasodilation and .microvascular permeability. Over-expression of VEGF has been linked to poor prognosis in breast cancer, rheumatoid arthritis, diabetic retinopathy, age related macular degeneration and angiosarcoma. Targeting the VRGF signaling pathway is means of controlling tumor growth and metastasis. One of the ways in which this can be achieved is by inhibition of VEGF or VEGFR with small molecules. XL880 is a tyrosine kinase inhibitor which targets hepatocyte growth factor (HGF) and its endothelial receptor (MET). MET and VEGF co-operate to promote vascularization of tumors. Single therapy treatments against the VEGF pathway initially can be extremely effective but can lose effectiveness over time, the suggestion is that the MET pathway offers an escape route for cell survival when VEGF is inhibited. [Read the Full Post]

Effects of dovitinib on cancers

2617 | Nov 21 2011

As we all know, cancers are always accompanied by pathological abnormality, such as growth, proliferation and migration of cancer cells. Many factors, as the biomarkers and targets, have been reported to be involved in the process, such as VEGF, PDGF, FGF, and their receptors as well as their downstream signaling components. [Read the Full Post]

The roles of Midkine/Alk signaling in sympathetic neurons physiologically and pathologically

3951 | Oct 18 2011

Neuroblastoma(NB) is the most common extracranial solid cancer that arises in immature nerve cells, and thus often occurs in childhood and infancy, with an incidence of about 650 new cases per year in US. Some evidences suggested that disposition and process of NB may be associated to proliferation of immature sympathetic neurons regulated by some transcription factors. [Read the Full Post]

FLT3 ligand enhances efficacy of RNA Vaccines in cancer therapy

4092 | Sep 14 2011

Vaccines work on the principle of promote the immune system to recognize an invader and attack it more quickly, before it can do any harm. Recently, self-replicating RNA vaccines have emerged as an effective and safe approach to induce antitumor immunity. Self-replicating RNA can replicate in a diverse range of cell types, allows the expression of the Ag of interest at high levels, and eventually causes lysis of transfected cells. [Read the Full Post]

Alexander V. Sirotkin “The role of protein kinases in control of ovarian functions”

2662 | Sep 13 2011

Control of basic physiological processes including reproduction requires multilevel signaling system, which includes hormones, growth factors and related molecules, their receptors and binding proteins, whose alter expression of target genes via protein kinases (PKs) and transcription factors. These signaling substances can control reproductive processes via production, binding and metabolism of regulators of cell cycle, apoptosis, secretory activity, differentiation and oogenesis. [Read the Full Post]

FGFs and the downstream signaling involve in tissue regeneration

4078 | Sep 06 2011

FGFs have the biological activity of inducing cell proliferation, migration, differentiation, and angiogenesis. As one of the critical components in tissue regeneration, fibroblast growth factors (FGFs) shown the potential effects on the repair and regeneration of tissues. [Read the Full Post]

Shaw, A. T. and B. Solomon (2011). "Targeting anaplastic lymphoma kinase in lung cancer." Clin Cancer Res 17(8): 2081-2086.

3697 | Aug 19 2011

This article reviews the ALK pathway and the Clinical–Translational Advances of different ALK inhibitors. [Read the Full Post]

Huang, H., A. Bhat, et al. (2010). "Targeting the ANGPT-TIE2 pathway in malignancy." Nat Rev Cancer 10(8): 575-585.

3209 | Jul 20 2011

This article which is published in Nature review cancer introduce the role of Tie2 in signal transduction such as angiogenesis. It also concludes the inhibitors of Tie2 kinase in cancer therapeutics. [Read the Full Post]

Chiarle, R., C. Voena, et al. (2008). "The anaplastic lymphoma kinase in the pathogenesis of cancer." Nat Rev Cancer 8(1): 11-23.

4114 | Jul 19 2011

This review which was published in Nature Reviews Cancer concludes the pathways which ALK is involved in and targets that ALK is related to. The content also includes ALK as a therapeutic target in cancer. [Read the Full Post]

Padera, T. P. and R. K. Jain (2008). "VEGFR3: a new target for antiangiogenesis therapy?" Dev Cell 15(2): 178-179.

2156 | Jun 13 2011

This review is about VEGFR-3,which are related to Notch pathway. It concludes a article which is published in Nature about VEGFR-3. [Read the Full Post]

Bianco, R., T. Gelardi, et al. (2007). "Rational bases for the development of EGFR inhibitors for cancer treatment." Int J Biochem Cell Biol 39(7-8): 1416-1431.

3163 | May 11 2011

This article reviews the EGFR role in carcinogenesis and tumor progression as rational bases for the development of specific therapeutic inhibitors. [Read the Full Post]

Holmes, K., O. L. Roberts, et al. (2007). "Vascular endothelial growth factor receptor-2: structure, function, intracellular signalling and therapeutic inhibition." Cell Signal 19(10): 2003-2012.

2233 | May 3 2011

This article explains the function of VEGFR-2 and the relationship among VEGFR, bcl-2, p53 and caspase. We can also learn the relationship between VEGFR and different diseases. [Read the Full Post]

Markovic, A., K. L. MacKenzie, et al. (2005). "FLT-3: a new focus in the understanding of acute leukemia." Int J Biochem Cell Biol 37(6): 1168-1172.

4028 | Apr 20 2011

This review introduces the FLT-3 signaling cascade, the process of activation, internalization, and degradation of FLT-3, and medical applications of FLT-3 inhibitors. [Read the Full Post]

Gilliland, D. G. and J. D. Griffin (2002). "The roles of FLT3 in hematopoiesis and leukemia." Blood 100(5): 1532-1542.

3920 | Mar 14 2011

This review provides comprehensive coverage of the role that FLT3 in hematopoiesis and leukemia and how the FLT-3 inhibitors work in treatment of hematopoiesis and leukemia. [Read the Full Post]

Fischer, O. M., S. Hart, et al. (2003). "EGFR signal transactivation in cancer cells." Biochem Soc Trans 31(Pt 6): 1203-1208.

3096 | Mar 11 2011

Together with investigations revealing the importance of this GPCR-EGFR cross-talk mechanism in cardiac hypertrophy, Helicobacter pylori -induced pathophysiological processes and cystic fibrosis, these findings support an important role for GPCR ligand-dependent EGFR signal transactivation in diverse pathophysiological disorders. [Read the Full Post]