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TGF-beta/Smad

Alkylation of Staurosporine to Derive a Kinase Probe for Fluorescence Applications

1 | Aug 18 2019

Disney AJ et al. reported that this fluorescein-staurosporine conjugate binds to cAMP-dependent protein kinase in the nanomolar range. Furthermore, its binding can be antagonised with unmodified staurosporine as well as ATP, indicating it targets the ATP binding site in a similar fashion to native staurosporine. This reagent has potential application as a screening tool for protein kinases of interest. [Read the Full Post]

First-in-human dose study of the novel transforming growth factor-β receptor I kinase inhibitor LY2157299 monohydrate in patients with advanced cancer and glioma

1 | Aug 12 2019

Rodon J et al. showed that on the basis of the safety, pharmacokinetics, and antitumor activity in patients with glioma, the intermittent administration of LY2157299 at 300 mg/day is safe for future clinical investigation. [Read the Full Post]

Clinical development of galunisertib (LY2157299 monohydrate), a small molecule inhibitor of transforming growth factor-beta signaling pathway

6 | Aug 11 2019

Herbertz S et al. summarized the past and current experiences with different pharmacological treatments that enabled galunisertib to be investigated in patients. [Read the Full Post]

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

45 | 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]

Radiosensitization of Non-Small Cell Lung Cancer Cells by Inhibition of TGF-β1 Signaling With SB431542 Is Dependent on p53 Status

11 | Jul 22 2019

Zhao Y et al. concluded that the radiosensitizing effect of inhibition of TGF-β1 signaling in NSCLC cells by SB431542 was p53 dependent, suggesting that using TGF-β1 inhibitor in radiotherapy may be more complicated than previously thought and may need further investigation. [Read the Full Post]

Airway Progenitor Clone Formation Is Enhanced by Y-27632-Dependent Changes in the Transcriptome

18 | Jul 10 2019

Reynolds SD et al. concluded that Y-27632 fundamentally alters cell-cell and cell-ECM interactions, which preserves basal progenitor cells and allows greater cell amplification. [Read the Full Post]

Disposition of asciminib, a potent BCR-ABL1 tyrosine kinase inhibitor, in healthy male subjects

18 | Jun 30 2019

Tran P et al. presented the results of human oral absorption, distribution, metabolism, excretion (ADME) and in vitro studies that together provide an overall understanding of the metabolism, distribution and clearance of asciminib in humans. [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

43 | 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]

Midostaurin plus Chemotherapy for Acute Myeloid Leukemia with a FLT3 Mutation

66 | Jun 07 2019

Stone RM et al. indicated the addition of the multitargeted kinase inhibitor midostaurin to standard chemotherapy significantly prolonged overall and event-free survival among patients with AML and a FLT3 mutation. [Read the Full Post]

Small molecules dorsomorphin and LDN-193189 inhibit myostatin/GDF8 signaling and promote functional myoblast differentiation

35 | Jun 05 2019

Horbelt D et al. suggested these inhibitors as suitable tools to promote functional myogenesis. [Read the Full Post]

KD025 (SLx-2119) suppresses adipogenesis at intermediate stage in human adipose-derived stem cells

69 | May 31 2019

Diep DTV et al. indicated that KD025suppresses adipocyte differentiation by modulation of key factors activated at the intermediate stage of differentiation, and not by inhibition of ROCK2. [Read the Full Post]

Midostaurin/PKC412 for the treatment of newly diagnosed FLT3 mutation-positive acute myeloid leukemia

51 | May 25 2019

Luskin MR et al. indicated that expert commentary: The approval of midostaurin represents the first new therapy for AML in several decades. It is also the first targeted therapy approved for AML. Future studies will focus on defining mechanisms of resistance to midostaurin as well as establishing the role of midostaurin in combination with hypomethylating agents and as maintenance therapy. Second generation, more potent and selective FLT3 inhibitors are also in development; these agents need to be compared to midostaurin. [Read the Full Post]

Clinical development of galunisertib (LY2157299 monohydrate), a small molecule inhibitor of transforming growth factor-beta signaling pathway.

51 | May 17 2019

Herbertz S et al. summarized the past and current experiences with different pharmacological treatments that enabled galunisertib to be investigated in patients. [Read the Full Post]

First-in-human dose study of the novel transforming growth factor-β receptor I kinase inhibitor LY2157299 monohydrate in patients with advanced cancer and glioma

59 | May 16 2019

On the basis of the safety, pharmacokinetics, and antitumor activity in patients with glioma, the intermittent administration of LY2157299 at 300 mg/day is safe for future clinical investigation. [Read the Full Post]

Embryonic stem cells differentiated into neuron-like cells using SB431542 small molecule on nanofibrous PLA/CS/Wax scaffold

61 | May 03 2019

Hoveizi E et al. revealed that electrospun PLA/CS/Wax scaffolds associated with the induction medium can assemble proper conditions for stem cell differentiation into NLCs. [Read the Full Post]

Grem2 mediates podocyte apoptosis in high glucose milieu

98 | Apr 02 2019

Wen H et al. indicated high glucose increases Grem2 expression in kidney cells. Grem2 mediates podocyte apoptosis through Smads. [Read the Full Post]

Mechanisms of U46619-induced contraction in mice intrarenal arteries

143 | Mar 27 2019

Yan H et al. suggested that the U46619-induced contraction of mouse intrarenal arteries is mediated by Cav1.2 and SOC channel, through the activation of thromboxane-prostanoid receptors and its downstream signaling pathway. [Read the Full Post]

Generation of Urine Cell-Derived Non-integrative Human iPSCs and iNSCs: A Step-by-Step Optimized Protocol

124 | Mar 24 2019

Cheng L et al. showed the optimized protocol is an easy and fast procedure to yield both iPSC and iNSC lines from a convenient source of human urine in a single experiment. [Read the Full Post]

Sotrastaurin in calcineurin inhibitor-free regimen using everolimus in de novo kidney transplant recipients

97 | Mar 03 2019

Tedesco-Silva H et al. indicated that sotrastaurin combined with EVR showed higher efficacy failure rates and some improvement in renal allograft function compared to a CsA-based therapy. [Read the Full Post]

LY2109761 inhibits metastasis and enhances chemosensitivity in osteosarcoma MG-63 cells

111 | Feb 27 2019

Ren XF et al. indicated that LY2109761 suppresses OS metastasis and enhanced chemosensitivity by targeting S100A4. LY2109761 may have important implications for the development of strategies for inhibiting metastasis and overcoming OS cell resistance to chemotherapy. [Read the Full Post]

Pharmacology and pharmacokinetics of imatinib in pediatric patients

304 | 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]

PI3K Catalytic Isoform Alteration Promotes the LIMK1-related Metastasis Through the PAK1 or ROCK1/2 Activation in Cigarette Smoke-exposed Ovarian Cancer Cells

0 | Dec 18 2018

Park GB et al. showed that characterization of the p110 isotypes of PI3K is critical for regulating cancer metastasis; LIMK1 could be a common therapeutic target of ovarian cancer metastasis. [Read the Full Post]

Testosterone improves the differentiation efficiency of insulin-producing cells from human induced pluripotent stem cells

161 | Dec 12 2018

Liu H et al. found that T improves the differentiation efficiency of insulin-producing cells from hiPSCs. The addition of T into routine differentiation formula for pancreatic β cells increases the differentiation efficiency from 12% to 35%. The administration of T promotes the expression of key genes associated with β cells differentiation including NGN3, NEUROD1 and INS. This finding benefits the ongoing process to optimize the differentiation protocol of pancreatic β cells from hiPSCs, and provides some degree of understanding the clinical management of T for type 2 diabetes. [Read the Full Post]

TGF-β sensu stricto signaling regulates skeletal morphogenesis in the sea urchin embryo

480 | Dec 11 2018

Sun Z et al. revealed that this model morphogenetic process involves an even more diverse suite of cell signaling pathways than previously appreciated and show that PMCs integrate a complex set of both generalized and spatially localized cues in assembling the endoskeleton. [Read the Full Post]

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

1579 | 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]

Treatment to sustain a Th17-type phenotype to prevent skewing toward Treg and to limit premalignant lesion progression to cancer

249 | Nov 05 2018

Young MR et al. showed that the treatment approach not only sustained the Th17 phenotype, but also increased distal spleen cell and regional lymph node cell production of other stimulatory/inflammatory mediators and slowed premalignant lesion progression to cancer. [Read the Full Post]

Vitamin D prevents articular cartilage erosion by regulating collagen II turnover through TGF-β1 in ovariectomized rats

230 | Nov 02 2018

Li S et al. showed protective effects in OVX-induced OA partly through the TGF-β1 pathway. [Read the Full Post]

Retinoic acid and TGF-β signalling cooperate to overcome MYCN-induced retinoid resistance

537 | Oct 15 2018

Duffy DJ et al. provided a powerful precision oncology tool for identifying the driving signalling networks for malignancies not primarily driven by somatic mutations, such as paediatric cancers. By applying global omics approaches to the signalling networks regulating neuroblastoma differentiation and stemness, we have determined the pathways involved in the MYCN-mediated retinoid resistance, with TGF-β signalling being a key regulator. These findings revealed a number of combination treatments likely to improve clinical response to retinoid therapy, including co-treatment with retinoids and KGN, which may prove valuable in the treatment of high-risk MYCN-amplified neuroblastoma. [Read the Full Post]

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

737 | 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]

TGF-β and NF-κB signaling pathway crosstalk potentiates corneal epithelial senescence through an RNA stress response

325 | Sep 29 2018

Li ZY et al. indicated that TGF-β-driven NF-κB activation contributes to corneal epithelial senescence via RNA metabolism and the inflammation blockade can attenuate TGF-β-induced senescence. [Read the Full Post]

Upregulation of programmed cell death ligand 1 promotes resistance response in non-small-cell lung cancer patients treated with neo-adjuvant chemotherapy

1099 | Aug 26 2018

Zhang P et al. suggested that the upregulation of PD-L1 promotes a resistance response in lung cancer cells that might be through activation of the phosphatidylinositol 3-kinase/protein kinase B pathway and suppression of tumor-infiltrating lymphocytes. The high expression of PD-L1 after NAC could be an indication of therapeutic resistance and poor prognosis in patients with non-small-cell lung cancer. [Read the Full Post]

MKP1 mediates chemosensitizer effects of E1a in response to cisplatin in non-small cell lung carcinoma cells

408 | Aug 05 2018

Cimas FJ et al. indicated that the present work reinforce the critical role of MKP1 in the cellular response to cisplatin highlighting the importance of this phosphatase in future gene therapy approach based on E1a gene. [Read the Full Post]

Inhibiting PLK1 induces autophagy of acute myeloid leukemia cells via mammalian target of rapamycin pathway dephosphorylation

793 | Jul 10 2018

Tao YF et al. provided new insights into the molecular mechanism of PLK1 in regulating autophagy. [Read the Full Post]

Fibroblastic foci, covered with alveolar epithelia exhibiting epithelial-mesenchymal transition, destroy alveolar septa by disrupting blood flow in idiopathic pulmonary fibrosis

495 | Jul 10 2018

Yamaguchi M et al. showed that inhibition of transforming growth factor-β signaling, which can suppress EMT of the alveolar epithelial cells in vitro, is a potential strategy for treating IPF. [Read the Full Post]

AT13148, a first-in-class multi-AGC kinase inhibitor, potently inhibits gastric cancer cells both in vitro and in vivo

1734 | Jun 20 2018

Xi Y et al. supported the progression of this molecule into future evaluation as a valuable anti-gastric cancer candidate. [Read the Full Post]

Inhibition of deubiquitinases primes glioblastoma cells to apoptosis in vitro and in vivo

792 | Jun 18 2018

Karpel-Massler G et al. suggested that targeting deubiquitinases for glioma therapy is feasible and effective. [Read the Full Post]

The Deubiquitinase USP9X Maintains DNA Replication Fork Stability and DNA Damage Checkpoint Responses by Regulating CLASPIN during S-Phase

871 | Jun 18 2018

McGarry E et al. revealed a novel role for USP9X in the maintenance of genomic stability during DNA replication and provide potential mechanistic insights into its tumor suppressor role in certain malignancies. [Read the Full Post]

Epithelial-mesenchymal transition confers resistance to selective FGFR inhibitors in SNU-16 gastric cancer cells

0 | May 21 2018

Grygielewicz P et al. provided experimental evidence that EMT-mediated resistance might emerge in gastric cancer patients following treatment with FGFR inhibitors, and mubritinib or AUY922 treatment may be an alternative therapeutic strategy for these patients. [Read the Full Post]

Long non-coding RNA NKILA inhibits migration and invasion of non-small cell lung cancer via NF-κB/Snail pathway

1388 | May 17 2018

Lu Z et al. found that the expression of NKILA was downregulated in tumor tissues of NSCLC, which improved the metastasis of NSCLC patients. In vitro studies further clarified that the expression of NKILA was regulated through classical TGF-β signal pathway, which subsequently inhibited migration and invasion of NSCLC cells through interfering NF-κB/Snail signal pathway in NSCLC cells. [Read the Full Post]

FAM83D associates with high tumor recurrence after liver transplantation involving expansion of CD44+ carcinoma stem cells

0 | May 17 2018

Lin B et al. indicated that FAM83D promotes HCC recurrence by promoting CD44 expression and CD44+ CSCs malignancy. FAM83D provides a novel therapeutic approach against HCC recurrence after LT. [Read the Full Post]

Jumonji AT-rich interactive domain 1B overexpression is associated with the development and progression of glioma

504 | May 05 2018

Fang L et al. suggested that JARID1B is involved in the pathogenesis of glioma, and that the downregulation of JARID1B in glioma cells may be a therapeutic target for the treatment of patients with glioma. [Read the Full Post]

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

1780 | 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]

Regulation of glutamate transporter trafficking by Nedd4-2 in a Parkinson's disease model

0 | Mar 23 2018

Zhang Y et al. indicated that Nedd4-2 may serve as a potential therapeutic target for the treatment of PD. [Read the Full Post]

A Novel Antifibrotic Mechanism of Nintedanib and Pirfenidone. Inhibition of Collagen Fibril Assembly

775 | Mar 12 2018

Knüppel L et al. indicated both drugs act on important regulatory levels in collagen synthesis and processing. Nintedanib was more effective in down-regulating profibrotic gene expression and collagen secretion. Importantly, both drugs inhibited collagen I fibril formation and caused a reduction in and an altered appearance of collagen fibril bundles, representing a completely novel mechanism of action for both drugs. [Read the Full Post]

Survivin inhibitor YM155 induces mitochondrial dysfunction, autophagy, DNA damage and apoptosis in Bcl-xL silenced glioma cell lines

785 | Feb 14 2018

Jane EP et al. provided a new insight into the link between Bcl-xL and survivin inhibition for the development of novel therapies for glioma. [Read the Full Post]

Ligation of CD180 inhibits IFN-α signaling in a Lyn-PI3K-BTK-dependent manner in B cells

1556 | Feb 14 2018

You M et al. provided molecular insight into the mechanism of IFN-α signaling activation in SLE B cells and a potential therapeutic approach for SLE treatment. [Read the Full Post]

Inhibition of TGF-β signaling promotes expansion of human epidermal keratinocytes in feeder cell co-culture

628 | Feb 10 2018

Suzuki D et al. found important implications for the use of TGF-β signaling inhibition as a viable therapeutic strategy for improving Green's methodology and for more efficient production of customized skin autografts with human feeder cells. [Read the Full Post]

Cocktail of chemical compounds robustly promoting cell reprogramming protects liver against acute injury

598 | Feb 05 2018

Tang Y et al. offered proof-of-concept evidence that cocktail of clinical compounds improving cell reprogramming favors tissue recovery after acute damages, which is an attractive strategy for regenerative purpose. [Read the Full Post]

Differentiation of induced pluripotent stem cell-derived neutrophil granulocytes from common marmoset monkey (Callithrix jacchus).

1159 | Jan 27 2018

Schrimpf C et al. indicated cj-iPSC-derived neutrophils bare high hopes in hematologic cell replacement therapy. They exhibit high morphologic similarity to native neutrophils and present neutrophil-specific surface antigens, antimicrobial proteins, and gene products yielding an auspicious approach for continuative experiments including tests in living animals. [Read the Full Post]

CK1δ kinase activity is modulated by protein kinase C α (PKCα)-mediated site-specific phosphorylation

1759 | Jan 14 2018

Meng Z et al. contributed to a deeper understanding of cellular signal transduction networks thereby helping to form a basis for the development of future therapeutic concepts. [Read the Full Post]

Extracellular heat shock protein 90α mediates HDM-induced bronchial epithelial barrier dysfunction by activating RhoA/MLC signaling

924 | Jan 04 2018

Dong HM et al. suggested that eHsp90α is a potential therapeutic target for treatment of asthma. [Read the Full Post]

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

1639 | 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]

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

3174 | Dec 10 2017

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

Integrative Network Analysis Combined with Quantitative Phosphoproteomics Reveals Transforming Growth Factor-beta Receptor type-2 (TGFBR2) as a Novel Regulator of Glioblastoma Stem Cell Properties

705 | Nov 28 2017

Narushima Y et al. indicated that transforming growth factor-β receptor type-2 could play an important role as a novel cell fate determinant in glioblastoma stem cell regulation. [Read the Full Post]

Activation of anaphase-promoting complex by p53 induces a state of dormancy in cancer cells against chemotherapeutic stress

891 | Nov 28 2017

Dai Y et al. provided a mechanism to unravel cancer cell dormancy and reactivation of the cancer cell population. [Read the Full Post]

AZGP1 suppresses epithelial-to-mesenchymal transition and hepatic carcinogenesis by blocking TGFβ1-ERK2 pathways

1984 | Nov 19 2017

Xu MY et al. showed that loss of AZGP1 could trigger EMT induced by TGFβ1-ERK2 signaling, confuse in energy metabolism, reduce cell proliferation and apoptosis, activate survival signals and promote invasion. Up-regulation of AZGP1 should be proposed to reverse EMT and might be a new promising therapy for HCC. [Read the Full Post]

Targeting protein kinase C in mantle cell lymphoma

945 | Nov 16 2017

Rauert-Wunderlich H et al. showed that MCL cells are heterogeneous in their response to BTK or PKC inhibition, indicating the need for even more individualized targeted treatment approaches in subsets of MCL patients. [Read the Full Post]

Synergistic effects of selective inhibitors targeting the PI3K/AKT/mTOR pathway or NUP214-ABL1 fusion protein in human Acute Lymphoblastic Leukemia

0 | Nov 08 2017

Simioni C et al. indicated that co-targeting NUP214-ABL1 fusion gene and PI3K/Akt/mTOR signaling pathway could represent a new and effective pharmacological strategy to improve the outcome in NUP214-ABL1 positive T-ALL. [Read the Full Post]

Transforming growth factor-β1 suppresses bone morphogenetic protein-2-induced mesenchymal-epithelial transition in HSC-4 human oral squamous cell carcinoma cells via Smad1/5/9 pathway suppression

939 | Oct 21 2017

Chiba T et al. suggested that TGF-β positively regulates hOSCC invasion in the primary tumor, whereas BMP-2 facilitates cancer cell colonization at secondary metastatic sites. Thus, the invasive and metastatic characteristics of hOSCC appear to be reciprocally regulated by BMP and TGF-β. [Read the Full Post]

Cytokine correlation analysis based on drug perturbation

0 | Oct 19 2017

Wallner FK et al. showed that cytokines are highly co-regulated, which provide valuable information for how a therapeutic drug might affect clusters of cytokines. In addition, a cytokine that is used as a therapeutic biomarker could be combined with its related cytokines into a biomarker panel to improve diagnostic accuracy. [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]

Anterior-Posterior Patterning of Definitive Endoderm Generated from Human Embryonic Stem Cells Depends on the Differential Signaling of Retinoic Acid, Wnt-, and BMP-Signaling

1148 | Sep 10 2017

Davenport C et al. provided new insights into the mechanisms behind cell specification of human DE derived from pluripotent stem cells. VHL deficiency is dependent on HIF activation. Moreover, HIF1α or HIF2α overexpression in CC-RCCVHL cells is sufficient to sensitize them to ROCK inhibition. Finally, Y-27632 treatment inhibited growth of subcutaneous 786-OT1 CC-RCC tumors in mice. Thus, ROCK inhibitors represent potential therapeutics for VHL-deficient CC-RCC. [Read the Full Post]

Rho-associated kinase 1 inhibition is synthetically lethal with von Hippel-Lindau deficiency in clear cell renal cell carcinoma

1527 | Sep 09 2017

Thompson JM et al. suggested that synthetic lethality between ROCK inhibition and VHL deficiency is dependent on HIF activation. Moreover, HIF1α or HIF2α overexpression in CC-RCCVHL cells is sufficient to sensitize them to ROCK inhibition. Finally, Y-27632 treatment inhibited growth of subcutaneous 786-OT1 CC-RCC tumors in mice. Thus, ROCK inhibitors represent potential therapeutics for VHL-deficient CC-RCC. [Read the Full Post]

Synergistic effects of selective inhibitors targeting the PI3K/AKT/mTOR pathway or NUP214-ABL1 fusion protein in human Acute Lymphoblastic Leukemia

2180 | Sep 01 2017

Simioni C et al. showed that dephosphorylation of pAkt and pS6 showed the cytotoxicity of these compounds. Either single or combined administration of drugs against the different targets displayed inhibition of cellular viability associated with a concentration-dependent induction of apoptosis, cell cycle arrest in G0/G1 phase and autophagy, having the combined treatments a significant synergistic cytotoxic effect. Co-targeting NUP214-ABL1 fusion gene and PI3K/Akt/mTOR signaling pathway could represent a new and effective pharmacological strategy to improve the outcome in NUP214-ABL1 positive T-ALL. [Read the Full Post]

Cell Death Induction by the Indirubin Derivative 7BIO and the BH3 Mimetic Drugs ABT-737 and GX15-070 in Medullary Thyroid Carcinoma Cells

1887 | Aug 15 2017

Broecker-Preuss M et al. showed that although the exact kind of cell death and target molecules of 7BIO and GX15-070 are not yet defined, direct induction of cell death may be a new therapeutic option in medullary thyroid carcinoma cells. [Read the Full Post]

A novel sgRNA selection system for CRISPR-Cas9 in mammalian cells

1938 | Aug 14 2017

Zhang H et al. provided a potential application to optimize the sgRNAs in different species and to generate a powerful CRISPR-Cas9 genome-wide screening system with minimum amounts of sgRNAs. [Read the Full Post]

Image-Guided Radiotherapy Targets Macromolecules through Altering the Tumor Microenvironment

2096 | 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

2067 | 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]

Synergistic effects of CD44 and TGF-β1 through AKT/GSK-3β/β-catenin signaling during epithelial-mesenchymal transition in liver cancer cells

966 | Jul 21 2017

Park NR et al. demonstrated the synergistic interactions between CD44 and TGF-β1 in EMT induction and CSC properties through the AKT/GSK-3β/β-catenin pathway in HCC cells. [Read the Full Post]

The positional identity of iPSC-derived neural progenitor cells along the anterior-posterior axis is controlled in a dosage-dependent manner by bFGF and EGF

0 | Jul 14 2017

Zhou S et al. indicated that different concentrations of bFGF and EGF supplemented during propagation of neural rosettes are involved in altering the identity of the resultant neural cells. [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

4572 | 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]

Exosomes derived from platelet-rich plasma promote the re-epithelization of chronic cutaneous wounds via activation of YAP in a diabetic rat model

2374 | Jun 06 2017

Guo SC et al. provided evidence of the probable molecular mechanisms underlying the PRP effect on healing of chronic ulcers and describe a promising resource of growth factors from exosomes without species restriction. [Read the Full Post]

Multiple Sclerosis Patient-Specific Primary Neurons Differentiated from Urinary Renal Epithelial Cells via Induced Pluripotent Stem Cells

0 | May 22 2017

Massa MG et al. provided an avenue for studies with a greater cell- and human-specific focus, specifically in the context of genetic contributions to neurodegeneration and drug discovery. [Read the Full Post]

Bafetinib (INNO-406) reverses multidrug resistance by inhibiting the efflux function of ABCB1 and ABCG2 transporters

1607 | May 22 2017

Zhang YK et al. found that bafetinib reversed ABCB1- and ABCG2-mediated MDR by blocking the drug efflux function of these transporters [Read the Full Post]

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

2831 | 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]

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

2609 | 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]

High glucose-induced Matrilin-2 expression in mouse mesangial cells was mediated by transforming growth factor beta 1 (TGF-β1).

1065 | Apr 24 2017

Zhang S et al showed that high-glucose-induced Matrilin-2 expression that was mediated by the TGF-β1/Smad3 signaling pathway might play a role in Diabetic nephropathy (DN) pathogenesis and our finding provided a potential diagnostic and/or therapeutic target for DN. [Read the Full Post]

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

4873 | 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]

Electrochemical biosensor for protein kinase A activity assay based on gold nanoparticles-carbon nanospheres, phos-tag-biotin and β-galactosidase

2186 | Apr 21 2017

Zhou Y et al. found the fabricated biosensor can be applied to detect PKA in human normal gastricepithelial cell line and human gastric carcinoma cell line with satisfactory results. [Read the Full Post]

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

5860 | 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]

Nicotine-Mediated Ca2+ -Influx Induces IL-8 Secretion in Oral Squamous Cell Carcinoma Cell

1994 | Mar 14 2017

Tsunoda K et al. suggested that the binding of nicotine to nAChR induces Ca(2+) influx, which results in the activation and phosphorylation of CaMK II and NF-κB p65, respectively. Nicotine-mediated IL-8 induction should be a trigger for the initiation of various diseases. [Read the Full Post]

Opposing roles of TGF-β and EGF in the regulation of TRAIL-induced apoptosis in human breast epithelial cells

1358 | Feb 15 2017

Li W et al. revealed a fine regulation by EGF and TGF-β of sensitivity of human breast epithelial cells to TRAIL which may be relevant during morphogenesis. [Read the Full Post]

Delocalized Claudin-1 promotes metastasis of human osteosarcoma cells

0 | Feb 12 2017

Jian Y, et al.'s study implied that delocalization of claudin-1 induced by PKC phosphorylation contributes to metastatic capacity of OS cells. [Read the Full Post]

Ph-like ALL-related novel fusion kinase ATF7IP-PDGFRB exhibits high sensitivity to tyrosine kinase inhibitors in murine cells.

0 | Feb 05 2017

Ishibashi T, et al.'s observations suggest the therapeutic importance of tyrosine kinase inhibitors and possibly MEK inhibitor for a subset of BCP-ALL harboring PDGFRB-related fusion kinases. [Read the Full Post]

Nicotine-Mediated Ca2+ -Influx Induces IL-8 Secretion in Oral Squamous Cell Carcinoma Cell

2260 | Jan 22 2017

The results fromTsunoda K, et al.'s study indicate that the binding of nicotine to nAChR induces Ca(2+) influx, which results in the activation and phosphorylation of CaMK II and NF-κB p65, respectively. Nicotine-mediated IL-8 induction should be a trigger for the initiation of various diseases. [Read the Full Post]

Delocalized Claudin-1 promotes metastasis of human osteosarcoma cells

2310 | Jan 05 2017

Jian Y, et al.'s our study implied that delocalization of claudin-1 induced by PKC phosphorylation contributes to metastatic capacity of OS cells. [Read the Full Post]

Ph-like ALL-related novel fusion kinase ATF7IP-PDGFRB exhibits high sensitivity to tyrosine kinase inhibitors in murine cells

2021 | Dec 29 2016

Ishibashi T, et al.‘’s observations suggest the therapeutic importance of tyrosine kinase inhibitors and possibly MEK inhibitor for a subset of BCP-ALL harboring PDGFRB-related fusion kinases. [Read the Full Post]

The positional identity of iPSC-derived neural progenitor cells along the anterior-posterior axis is controlled in a dosage-dependent manner by bFGF and EGF

2031 | Dec 17 2016

The results of Zhou S et al. indicated that different concentrations of bFGF and EGF supplemented during propagation of neural rosettes are involved in altering the identity of the resultant neural cells. [Read the Full Post]

Synergistic effects of CD44 and TGF-β1 through AKT/GSK-3β/β-catenin signaling during epithelial-mesenchymal transition in liver cancer cells

1641 | Dec 16 2016

Park NR, et al. demonstrated the synergistic interactions between CD44 and TGF-β1 in EMT induction and CSC properties through the AKT/GSK-3β/β-catenin pathway in HCC cells. [Read the Full Post]

Synergistic effects of CD44 and TGF-β1 through AKT/GSK-3β/β-catenin signaling during epithelial-mesenchymal transition in liver cancer cells

1691 | Dec 15 2016

Park NR et al.'s study demonstrated the synergistic interactions between CD44 and TGF-β1 in EMT induction and CSC properties through the AKT/GSK-3β/β-catenin pathway in HCC cells [Read the Full Post]

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

4310 | 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]

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

3635 | 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]

Opposing roles of TGF-β and EGF in the regulation of TRAIL-induced apoptosis in human breast epithelial cells

1691 | Nov 07 2016

Li W et al. revealed a fine regulation by EGF and TGF-β of sensitivity of human breast epithelial cells to TRAIL which may be relevant during morphogenesis. [Read the Full Post]

SB-224289 Antagonizes the Antifungal Mechanism of the Marine Depsipeptide Papuamide A

2383 | Oct 28 2016

[Read the Full Post]

Multiple Sclerosis Patient-Specific Primary Neurons Differentiated from Urinary Renal Epithelial Cells via Induced Pluripotent Stem Cells

3468 | Oct 19 2016

[Read the Full Post]

Bafetinib (INNO-406) reverses multidrug resistance by inhibiting the efflux function of ABCB1 and ABCG2 transporters

2247 | Oct 19 2016

Zhang YK et al. found that bafetinib reversed ABCB1- and ABCG2-mediated MDR by blocking the drug efflux function of these transporters. [Read the Full Post]

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

3440 | 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]

High glucose-induced Matrilin-2 expression in mouse mesangial cells was mediated by transforming growth factor beta 1 (TGF-β1)

1645 | Sep 26 2016

Zhang S et al. found that high-glucose-induced Matrilin-2 expression that was mediated by the TGF-β1/Smad3 signaling pathway might play a role in Diabetic nephropathy (DN) pathogenesis. [Read the Full Post]

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

1792 | Sep 22 2016

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]

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

2578 | 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]

Inhibition of proteasome restores bortesomib-induced thrombocytopenia

8489 | Feb 10 2015

Shi et al. reported clinical proteasome inhibitor enable to block proplatelet formation by megakaryocytes in human and mouse model. [Read the Full Post]

Star27 overcomes synthetic lethal toxicity for FLT3-targeted therapy against acute myeloid leukemia

4019 | Feb 06 2015

For overcoming myelosuppression, Warkentin et al. reported a staurosporine analog, Star27, that enable to inhibit FLT3 while avoiding KIT inhibition. [Read the Full Post]

A protocol for human pluripotent stem cell differentiation into endoderm related cells

6017 | Feb 02 2015

Diekmann et al. showed a detailed protocol started from a defined cell number of dispersed single cells of three different human ESC lines, and one human iPSC line. [Read the Full Post]

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

12054 | 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]

BUB1 plays a key role in promoting TGF-β signaling

5877 | Jan 20 2015

By using human kinome siRNA screen and a live-cell reporter for TGF-β receptor (TGFBR) activity, Nyati et al. identified the kinase budding uninhibited by benzimidazoles-1 (BUB1) plays a critical role in regulating TGF-β signaling. [Read the Full Post]

Generate hypothalamic neurons from hESCs and human iPSCs

3230 | Jan 08 2015

Wang et al. reported a protocol of differeiciating human embryonic stem cells (hESCs) and induced pluripotent stem cells (iPSCs) into hypothalamic cells. [Read the Full Post]

The important role of HSF1 expressed by cancer-associated fibroblasts

3355 | Dec 29 2014

Scherz-Shouval et al. found cancer-associated fibroblasts (CAFs) frequently express heat shock factor 1 (HSF1), which acts as a strong enabler of tumorigenesis. [Read the Full Post]

Innate immunity-induced IRF3 signaling suppress TGF-β via Smad

4696 | Dec 23 2014

By investigating the innate host defense, Xu et al. found RIG-I-Like receptor (RLR) signaling suppress TGF-β via activation of Interferon regulatory factor 3 (IRF3). [Read the Full Post]

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

8119 | 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]

The activation of BMP and WNT signals specifies epicardial lineage from hESCs

5873 | Nov 12 2014

Witty et al. describe a new strategy of using human pluripotent stem cells (hESCs) to generate epicardial lineage cells by activation the BMP and WNT signaling pathways in a stage-specific way. [Read the Full Post]

New platform of high efficiency iPSC reprogramming

7307 | Nov 05 2014

Vidal et al. found the inhibition of transforming growth factor β (TGF-β) or activation of Wnt signaling, or both, can provide a high efficient iPSC reprogramming in a cell-type-specific manner. [Read the Full Post]

The role of TGFβ target——LTBP4 in muscular dystrophy

3498 | Oct 24 2014

Ceco et al. found latent transforming growth factor-β (TGFβ) binding proteins 4 (LTBP4) play determinant roles in muscular dystrophy symptoms.Their data suggested that blocking LTBP4 results in reduced TGFβ release, and then leads to a reduction of muscle inflammation and damage in DMD. [Read the Full Post]

Y27632 is a biochemical tool used in the study of the ROCK

4956 | Mar 05 2014

Y-27632 2HCl inhibits ROCK-II while displaying little activity against PKC. [Read the Full Post]

SB431542 is a small molecule that acts as a specific inhibitor

3514 | Feb 13 2014

SB431542 is a potent and selective inhibitor of ALK5 with IC50 of 94 nM, 100-fold more selective for ALK5 than p38 MAPK and other kinases. [Read the Full Post]

SB525334 is a potent and selective inhibitor of TGFB

3377 | Feb 12 2014

SB 525334 (10 mg/kg/day) decreases the renal mRNA levels of PAI-1, procollagen α1(I), and procollagen α1(III) in a nephritis-induced renal fibrosis rat model. [Read the Full Post]

Y 27632 is available in a 5 mg format and has been optimized

4763 | Jan 17 2014

Y-27632 2HCl is a selective ROCK1 (p160ROCK) inhibitor with Ki of 140 nM, exhibits >200-fold selectivity over other kinases, including PKC, cAMP-dependent protein kinase, MLCK and PAK. [Read the Full Post]

Y 27632 is a biochemical tool used in the study of the rho associated protein kinase

4912 | Jan 10 2014

Y-27632 2HCl is a selective ROCK1 inhibitor with Ki of 140 nM, exhibits >200-fold selectivity over other kinases, including PKC, cAMP-dependent protein kinase, MLCK and PAK. [Read the Full Post]

SB 525334 is a selective inhibitor of transforming growth factor B

3075 | Dec 10 2013

SB525334 is a potent and selective inhibitor of TGFβ receptor I (ALK5) with IC50 of 14.3 nM, is 4-fold less potent to ALK4 than ALK5 and inactive to ALK2, 3, and 6. [Read the Full Post]

LDN193189 is a cell permeable

2909 | Dec 03 2013

LDN193189 is a selective BMP signaling inhibitor, inhibits the transcriptional activity of the BMP type I receptors ALK2 and ALK3 with IC50 of 5 nM and 30 nM, respectively, exhibits 200-fold selectivity for BMP versus TGF-β. [Read the Full Post]

Thiazovivin helps in promoting human embryonic stem cell

4662 | Nov 22 2013

Thiazovivin (Tzv) is a novel ROCK inhibitor with IC50 of 0.5 μM, promotes hESC survival after single-cell dissociation. [Read the Full Post]

Thiazovivin is a drug which dramatically improves the survival of hES

4937 | Nov 05 2013

Thiazovivin (Tzv) is a novel ROCK inhibitor with IC50 of 0.5 μM, promotes hESC survival after single-cell dissociation. [Read the Full Post]

Staurosporine is a potent PKC inhibitor with IC50

5033 | Sep 24 2013

Staurosporine, a microbial alkaloid, significantly inhibits protein kinase C from rat brain with IC50 of 2.7 nM. [Read the Full Post]

Y27632 is a selective inhibitor of the Rhoassociated kinase p160ROCK

4728 | Sep 12 2013

Y27632 2HCl inhibits ROCK-II while displaying little activity against PKC, cAMP-dependent protein kinase and myosin light-chain kinase (MLCK) with Ki of 26 μM, 25 μM and > 250 μM, respectively, as well as PKA activated by another Rho-family GTPase member, Cdc42. [Read the Full Post]

y27632 is a biochemical tool used in the study of the rho associated protein kinase signaling pathways

5202 | Jun 07 2013

Oral administration of Y-27632 2HCl at 30 mg/kg significantly decreases the blood pressure in a dose-dependent manner in spontaneous hypertensive rats, renal hypertensive rats, as well as deoxycorticosterone acetate (DOCA)-salt hypertensive rats. [Read the Full Post]

AEB071 is a potent selective pan PKC inhibitor

3890 | Jan 16 2013

Multiple sclerosis is a chronic and debilitating immune-mediated disease of the central nervous system . Recent epidemiological data supports the established view that the incidence of AEB071 MS peaks at about 30 years of age and that it is a disease with a positive female-to-male ratio. [Read the Full Post]

LY2109761 is a novel transforming growth factor

2749 | Jan 04 2013

The JAK2V617F mutated allele is present in virtually all patients with polycythemia vera (PV) and in about 60% of those with essential thrombocythemia (ET) and primary myelofibrosis (PMF), which are the other two main clinical entities included within the group of myeloproliferative LY2109761 neoplasms. [Read the Full Post]

PKC Inhibitors is associated with endothelial dysfunction

3981 | Dec 06 2012

Atherosclerosis is initiated by the deposition, retention and oxidative modification of apolipoprotein (apo)B-containing lipoproteins, notably low-density lipoprotein cholesterol (LDL-C) in the vessel wall. This is associated with endothelial PKC Inhibitors dysfunction and recruitment of monocytes that take up oxidised LDL to become macrophage-derived foam cells, collectively apparent macroscopically as "fatty streaks". [Read the Full Post]

ROCK Kinase is involved in cytokinesis

5087 | Dec 03 2012

The first evidence that the JNK pathway, the low level of expression in SMC Lon RGS4 ch Lt, then led end F F promotion from SMC contraction. Inhibition of tonic RGS4 expression by JNK pathway represents a novel mechanism for the contribution of the JNK pathway in the regulation of smooth muscle contraction. crosstalk between MAPK and JNK by other means NFkB not well ROCK Kinase understood. [Read the Full Post]

DASATINIB; An Inhibitor of Receptor Tyrosine Kinase

0 | Sep 06 2012

CHARACTERISTICS OF DASATINIB Experts and also scientists are trying hard to find improve drug that will be able to possess efficiency as against cancer which has become responsible of heavy death all over the world and also resistance towards the available drugs in cancer cells is also motivating scientists. Cancer cells avoid both the action of particular medicine by mutating themselves in a number of steps. Metastasis is actually also other problem related to disease. For chemotherapy of disease cell toxicity increases the problem. To attack these afore mentioned errors the only key to combat it to be able to devise new medication. Imatinib was used for many years but toxicity and other consequences mentioned above it obligate scientists to develop one less harmful and more efficient prescription. So in this respect Jagabandhu Das developed one medicine known as Dasatinib. Dasatinib BMS 354825 got very popular compared to Imatinib because of its less toxicity and more performance. It's developed through a pharmaceutical business Squibb and offered under the trade name on Sprycel. [Read the Full Post]

NILOTINIB AND PHILADELPHIA

5324 | Jul 25 2012

CML AND PHILADELPHIA CHROMOSOME During meiosis the fusion of two genes including BCR a breakpoint cluster and ABL tyrosine kinase results in the formation of Philadelphia chromosome. The resultant fusion protein expressed due to Philadelphia chromosome is not controlled and function abnormally leading to an oncoprotein. Chronic myelogenous leukemia or CML is caused by this fusion oncoprotein in 90% of the patients of CML. Due to huge part of this protein in CML, in drug development for cancer treatment this protein is being targeted by researchers by the help of small molecule screening. Nilotinib AMN-107 is one of the inhibitor used for this purpose to cure CML. [Read the Full Post]

NILOTINIB 

6041 | Jul 12 2012

ASSOCIATION OF PHILADELPHIA CHROMOSOME WITH CHRONIC MYELOGENOUS LEUKEMIA Philadelphia chromosome is composed by fusion of a tyrosine kinase ABL (Abelson) and BCR (break point cluster) gene during the cross linking of chromosomes in meiosis. This Philadelphia chromosome promotes fusion protein that functions in an uncontrolled manner as a tyrosine kinase making it an oncoprotein. This fusion oncoprotein is involved in causing CML i.e., chronic myelogenous leukemia in 90 % of patients of this disease. Due to the involvement of this fusion protein in CML, it is being targeted in lots of research going on for cancer therapeutics. Nilotinib bcr-abl inhibitor is one these inhibitors being used against CML. [Read the Full Post]

NILOTINIB

4914 | Jul 05 2012

CHRONIC MYELOGENOUS LEUKEMIA AND PHILADELPHIA CHROMOSOME During meiosis if BCR and tyrosine kinase ABL are unable to separate and fuse together it leads to condition called Philadelphia chromosome. Due to the fusion of these genes it leads to translation of abnormal protein which acts as malfunctioned tyrosine kinase that makes it oncoprotein. Around 90% of patients suffering from Ph+ also suffer from chronic myelogenous leukemia or CML. This fusion protein is being targeted for therapy of cancer since it is involved in CML and various researches are being carried out in this regard. An inhibitor of this protein is Nilotinib bcr-abl inhibitor which is used to treat CML. [Read the Full Post]

NILOTINIB

5775 | Jun 28 2012

CHRONIC MYELOGENOUS LEUKEMIA AND PHILADELPHIA CHROMOSOME During meiosis if BCR and tyrosine kinase ABL are unable to separate and fuse together it leads to condition called Philadelphia chromosome. Due to the fusion of these genes it leads to translation of abnormal protein which acts as malfunctioned tyrosine kinase that makes it oncoprotein. Around 90% of patients suffering from Ph+ also suffer from chronic myelogenous leukemia or CML. This fusion protein is being targeted for therapy of cancer since it is involved in CML and various researches are being carried out in this regard. An inhibitor of this protein is Nilotinib bcr-abl inhibitor which is used to treat CML. [Read the Full Post]

NILOTINIB AND PH+

5552 | Jun 10 2012

PHILADELPHIA CHROMOSOME AND CML Philadelphia chromosome is formed by fusion of a tyrosine kinase ABL (Abelson) and BCR (break point cluster) gene during the cross linking of chromosomes in meiosis. This Philadelphia chromosome gives rise to a fusion protein that is functions in an uncontrolled manner as a tyrosine kinase making it an oncoprotein. This fusion oncoprotein is involved in causing CML i.e., chronic myelogenous leukemia in 90 % of patients of this disease. Due to the involvement of this fusion protein in CML, it is being targeted in lots of research going on for cancer therapeutics. Nilotinib bcr-abl inhibitor is one these inhibitors being used against CML. [Read the Full Post]

DASATINIB- A DRUG OF CHOICE

5751 | Jun 04 2012

INTRODUCTION Diverse types of cellular systems are there in human bodies that differ structurally and functionally from one another. Each cellular system is controlled by a variety of controllers called cell cycle regulatory proteins. Defective controllers may lead to abnormal cellular systems and the condition known as cancer may develop. Cancer may be of different types depending upon the defect in the cell cycle regulatory proteins. Cancer may also vary on the basis of stage of the defective condition. Many therapies have been devised in order to treat cancerous cells. Further research is also being done for developing better, more specific and less toxic therapies and to cope with the development of resistance in the defective cells against existing therapies. Besides resistance, metastasis is also another issue to be resolved in case of cancerous cells. Imatinib has been used against leukemia for several years but due to high levels of toxicity scientists discovered a new drug, called Dasatinib, for the same therapy. Dasatinib BMS-354825 is more efficient and less toxic as compared to Imatinib. The drug is being marketed by the name of Sprycel. As Dasatinib was discovered by Jagabandhu Das, it was named Dasatinib. Development of the drug was done by Squibb Company. [Read the Full Post]

NILOTINIB

5689 | May 30 2012

ROLE OF BCR-ABL TYROSINE KINASES IN CML: A chimeric BCR-ABL oncogene is obtained by the fusion of Abelson (ABL) tyrosine kinase (TK) gene and break-point cluster (BCR) gene, and here TK has been related to pathogenesis of CML (Chronic Myelogenous Leukemia), 90% of this debilitating disease involves chromosomal abnormalities leading to formation of so-called Philadelphia chromosome. As there is a confirmed participation of BCR-ABL TK in PH+ CML, different inhibitors that target this TK have registered remarkable success in treatment of CML and among them Nilotinib bcr-abl inhibitor is the most valuable one. It is a form of tyrosine kinase inhibitor and is a hydrochloride monohydrate salt. [Read the Full Post]

IMATINIB – INHIBITS MULTIPLE KINASES

4880 | May 07 2012

INTRODUCTION: SRC inhibitors are the molecules specific for targeting the non rector tyrosine kinase enzymes of SRC family and have the potential of inhibiting the 2 or more members of two SRC subfamilies, Fyn, Src. Fgr, Yes, Lck, Blk, Frk and Hck SRC kinases. These kinase enzymes take part in various pathways, so targeting them has became an attractive and valuable approach in the field of chemotherapy. Imatinib is commonly known as STI-571. Imatinib SRC inhibitor is a molecule originally named as STI571 and marketed by the company Novartis in the form of its mesylate salt hence known as STI-571 Imatinib Mesylate. This salt form is especially developed for targeting the cancer cells sparing the normal cells from them hence developed as personalized drug. [Read the Full Post]

NILOTINIB

3623 | Apr 08 2012

ROLE OF BCR-ABL IN CML BCR (break-point cluster) and (ABL) Abelson genes code for the protein tyrosine kinases that are involved in signal transduction fusion of these two genes occur when a philadalphia chromosome is formed after some mistake in the process of crossing over. This chimeric oncogene is known as BCR-ABL and is known to be involved in the development of leukemia especially (CML) Chronic Myelogenous Leukemia. This type of fusion is known to be responsible for almost 90% CML cases and is known as PH+ CML. The participation of BCR-ABL in PH+ CML has urged the scientists to inhibit this fusion protein. Different types of inhibitors targeting this oncogenic fusion protein have been registered. Nilotinib Src-bcr-Abl inhibitor is one of such inhibitors against CML. [Read the Full Post]

STAUROSPORINE: A PKC INHIBITOR

5445 | Mar 25 2012

STAUROSPORINE PROPERTIES AND ORIGIN: The discovery of Staurosporine was done during the research on a bacterium Streptomyces staurosporeus in 1977, this compound was identified as an antibiotic and now this molecules has been studied thoroughly. Another alternate name of this molecule is STS or Staurosporine AM-2282, its configuration and structure was identified by certain physical techniques such as analysis of X-ray. Staurosporine PKC inhibitor is also found as active against a good number of protein kinases (PKs), Staurosporine IC50 for PKA, PKC and PKG is 7.0 nM, 0.7 nM and 8.5 nM respectively. When Staurosporine is stored at -20 oC it’s stability remains un-affected for two years. This compound is soluble in DMSO. Molecular weight of Staurosporine is 466.53 and it is expensive as Staurosporine price for 1 mg is more than $500, however the price is variable from one Staurosporine supplierto other. Staurosporine PKC inhibitor is available easily and if someone wants to purchase Staurosporine for laboratory and research use one can buy Staurosporine easily. [Read the Full Post]

ENZASTAURIN AGAINST MALIGNANCIES

3585 | Mar 20 2012

Introduction: The Protein Kinase C family A cytosolic protein kinase isolated in the late 1970’s by the Nishizuka group of Kobe University, Japan has been found to be a key factor in the regulation of the cell cycle. Established as the protein kinase C family several isoforms have subsequently be isolated. These serine / threonine kinases are activated by the diacylglycerol (DAG) which is generated by the agonist induced hydrolysis of Trans-membrane G-protein kinases or tyrosine kinases. Activation of protein kinase C leads to a movement of the protein to the either the cytosolic skeleton or to the cellular membrane triggering a cascade of downstream signals which induce cell growth, differentiation or proliferation activities, this process appears to be mediated by the release of Ca2+. One of the key elements to be discovered concerning this protein was the discovery that phorbol esters were also a ligand for activating this protein; this created a direct link between PKC and the formation of various tumors. [Read the Full Post]

THIAZOVIVIN: THE PLURIPOTENCY INDUCER

4042 | Mar 20 2012

POTENTIAL OF EMBRYONIC STEM CELLS OF HUMAN (hESCs): The stem cells are not only known for their property of pluripotency in nature which means they have the potency to replicate in an indefinite manner but also famous for their capability of getting differentiate into all other kinds of cells and organelles from the three basic germinal layers named as ectoderm, mesoderm and endoderm. Embryonic stem cells of human (hESCs) have the ability of producing various numbers of types of cells in contrast to adult stem cells having the capability of producing only a limited cell types. Due to their pluripotency hESCs or human embryonic stem cells are of great interest and importance for the scientists and researchers as they are being used for detection and analysis of different genetic disorders of human in their research. The successful models of Human Embryonic Stem Cells are made for Fragile-X syndrome and Cystic fibrosis (CF) etc like genetic maladies and their will be many more in upcoming years. In olden years the usual practice was to use embryo to generate pluripotent stem cells which is brought down very significantly due to the process of insertion of various genes like Sox2, Oct4 and Klf4 etc into differentiated cells. These genes can enhance the pluripotency in differentiated cells and make them exactly like embryonic stem cells. A recent more advanced approach is to use molecules like Thiazovivin. [Read the Full Post]

FINGOLIMOD – THE IMMUNOMODULATOR

3802 | Mar 19 2012

Introduction: Fingolimod and Multiple Sclerosis One of the most widely used fungi in Chinese herbal medication is the ascomycete “Isaria sinclairii”. Known for its medical properties for centauries it was examined more closely after the immunosuppressant cyclosporin was discovered from a fungal source. From a screening of the extracts from this fungus came the molecule myriocin which demonstrated immunosuppressant properties as hope, however, it also killed the host in animal models. This molecule proved to be far too toxic for clinical use hence the molecule skeleton was used as a template to derive a series of derivatives in the effort to reduce the toxicity but preserve the immunosuppression potency. From this process came FTY720 which was researched pre-clinically in the area of transplant rejection, before being released in clinical trials as Fingolimod . [Read the Full Post]

IMATINIB – THE MULTI KINASE INHIBITOR

3280 | Mar 19 2012

Introduction: The kinase super family In recent years the broadening of technology has enabled researchers to investigate the role of ligands in relation to cellular responses. To achieve understanding the binding properties, conformation changes, receptor response and protein binding domains similarity have been extensively researched, most notably in the field of oncology. The protein kinases are not really a new discovery but the relationship between proteins is now beginning to be understood. Over 500 different distinct proteins exist under the super family heading of protein kinases. These proteins govern the growth, proliferation, differentiation and apoptosis of nearly all aspects of the mammalian system. The protein kinase family is subdivided into small related protein series that seem to work together to receive a signal from an extracellular source and translated this into cellular activity. [Read the Full Post]

FTY720 – THE IMMUNE CELLS’ TRAFFIC CONTROLLER

3329 | Mar 19 2012

Introduction: Multiple Sclerosis Multiple sclerosis is probably a condition that everybody has heard off but not many really understand the cause or nature of this destructive disease. Basically this disease is what is known as an inflammatory disease which affects area of the lining in the spinal cord or brain stem. The effect of this is the slow degradation of the functions of the spinal cord and brain stem. This means a loss of motor control, loss of communicative functions, loss of sight and digestive difficulties. Accompanying these debilitating symptoms are almost constant pain and fatigue, life quality of most suffers becomes very poor. There is currently no known cure for this disease, while treatment focuses on alleviating the symptoms or retarding the progression of the disease but always the end point is the same. Patients with this disease are known to try any form of treatment scientifically proven or not in the hope a remission can be triggered. Remission is the peculiar aspect of this disease in that it appears in phases with periods of relative peace in-between. However, relapses are usually progressively worse accumulating damage to essential functions that cannot be repaired. [Read the Full Post]

DASATINIB – THE DOUBLE-EDGED SWORD

4217 | Mar 13 2012

Introduction: BCR-ABL and SCR targets Researchers are continuously searching for the magic compound which will cure all diseases but most know that this is a physical impossibility. Every disease is different and especially cancers where even tumors of the same site / type can be radically different. In CML, AML and ALL a mutation in two chromosomes has been linked to the onset of these diseases in a proportion of patients. The defect is referred to as the “Philadelphia chromosome”, here a section of chromosome 9 and chromosome 22 have swapped places (translocated). The end result is that chromosome 9 is longer than it should be while chromosome 22 is shorter than it should be. The significance of this change is that the coding for the BCR gene and the ABL gene become mixed up (fused). The protein from this genetic fusion is referred to as the BCR-ABL fusion protein. Studies have shown that this protein is related to the protein kinase super family and has serine / threonine kinase activity, it also has phosphorylation activity for the cytoskeletal enzyme p21 Rac (Cdc42). Imatinib is a small molecule inhibitor of the ABL in Chronic Myeloid Leukemia, Acute Myeloid Leukemia and Acute Lymphoblast Leukemia tumors that has been proven very successful in the clinic. However, patients with the translocated gene demonstrate resistance to Imatinib due in part to the nature of fused BCR-ABL gene. [Read the Full Post]

Enzastaurin, as the inhibitor of PKC, may be a novel PNC medical therapy

4321 | Sep 29 2011

Pancreatic cancer is the fourth most common cause of cancer death both in the United States. Regarding the pathology, pancreatic cancer mainly includes exocrine pancreas cancers, pancreatic cystic neoplasms and endocrine pancreatic cancers. Pancreatic neuroendocrine cancers (PNC) account for less than 3% of pancreatic tumors and the main treatments are surgery, hormone therapy, chemotherapy and so on at this stage. However, It is still needed to search for effective treatments for PNC, and understand the molecular pathways regulating neuroendocrine tumor cell proliferation. [Read the Full Post]

Rosse, C., M. Linch, et al. (2010). "PKC and the control of localized signal dynamics." Nat Rev Mol Cell Biol 11(2): 103-112.

4387 | Jul 19 2011

This review which was published in Nature review summary the role of PKC in different pathways and show the importance of PKCs in controlling spatial resolution in signaling processes using the MET and STAT3 example. [Read the Full Post]

Narumiya, S., M. Tanji, et al. (2009). "Rho signaling, ROCK and mDia1, in transformation, metastasis and invasion." Cancer Metastasis Rev 28(1-2): 65-76.

4870 | Jun 7 2011

This review summaries the Rho signaling in transformation, metastasis and invasion. It explains the relationship between Rho signaling and tumor cells, and it gives the perspectives in this review. [Read the Full Post]

Mackay, H. J. and C. J. Twelves (2007). "Targeting the protein kinase C family: are we there yet?" Nat Rev Cancer 7(7): 554-562.

4051 | May 18 2011

This review summary the development of PKC inhibitors for cancer. It also explains the difficulties we meet. The author also give a prospect of PKC inhibitors. [Read the Full Post]

Ren, R. (2005). "Mechanisms of BCR-ABL in the pathogenesis of chronic myelogenous leukaemia." Nat Rev Cancer 5(3): 172-183.

3642 | Apr 15 2011

The review which was published in Nature Review Cancer introduces the relationships between CML and BCR-ABL. The researchers introduce not only the BCR–ABL and oncogenic activities of BCR–ABL, roles of BCR–ABL domains in leukaemogenesis, but pathways downstream of BCR–ABL as well. [Read the Full Post]

Riento, K. and A. J. Ridley (2003). "Rocks: multifunctional kinases in cell behaviour." Nat Rev Mol Cell Biol 4(6): 446-456.

4229 | Mar 3 2011

This article introduces regulation of ROCK activity, ROCK function and ROCK inhibitors. This review concludes knowledge of ROCK in different ways. [Read the Full Post]