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Metabolism

BioID-screening identifies PEAK1 and SHP2 as components of the Alk "proximitome" in neuroblastoma cells

3 | Jul 22 2021

Ezgi Uçkun et al. noted a strong synergistic effect of combined ALK and SHP2 inhibition that was specific to ALK-driven NB cells, suggesting a potential therapeutic option for ALK-driven NB. [Read the Full Post]

Peptide 11R‑VIVIT promotes fracture healing in osteoporotic rats

4 | Jul 20 2021

Changju Hou et al. demonstrated that 11R‑VIVIT promoted fracture healing in osteoporotic rats and enhanced the osteogenic differentiation of osteoporotic BMSCs by dysregulating the AKT/NFATc1 signaling pathway. [Read the Full Post]

The Tumor Microenvironment in Follicular Lymphoma: Its Pro-Malignancy Role with Therapeutic Potential

8 | Jun 10 2021

Takashi Watanabe found that Tfh, and TFR cells could reinforce the effects of the cytotoxic T cells. [Read the Full Post]

cAMP Signaling-Mediated Phosphorylation of Diacylglycerol Lipase α Regulates Interaction With Ankyrin-G and Dendritic Spine Morphology

9 | Jun 09 2021

Sehyoun Yoon et al. found that ANK3 and DAGLA, both neuropsychiatric disorder genes, interacted in a complex to regulate spine morphology. [Read the Full Post]

Nonsense-mediated mRNA decay efficiency influences bleeding severity in ITGA2B c.2659C > T (p.Q887X) knock-in mice

12 | May 10 2021

Zhanli Xie et al. found that NMD efficiency potentially influenced bleeding severity in ITGA2B c.2659C > T (p.Q887X) KI mice. [Read the Full Post]

High BRCA2 Gene Expression is Associated with Aggressive and Highly Proliferative Breast Cancer

11 | May 10 2021

Vikas Satyananda et al. thought that BRCA2 gene expression might become a candidate marker for aggressive biology and to tailor specific treatment strategies in the future. [Read the Full Post]

Loss of FADD and Caspases Affects the Response of T-Cell Leukemia Jurkat Cells to Anti-Cancer Drugs

19 | Apr 26 2021

Zuzana Mrkvová et al. thought that a combination of TNF-α and smac mimetic could be a suitable strategy for overcoming resistance to therapy in cells unable to trigger apoptosis. [Read the Full Post]

Involvement of GLUT1 and GLUT3 in the growth of canine melanoma cells

19 | Apr 25 2021

Yoko Suwabe et al. suggested that glucose uptake via GLUT1 and GLUT3 played a crucial role for the growth of canine melanoma cells. [Read the Full Post]

A proprotein convertase subtilisin/kexin type 9 inhibitor provides comparable efficacy with lower detriment than statins on mitochondria of oxidative muscle of obese estrogen-deprived rats

18 | Apr 06 2021

Chanisa Thonusin et al. showed that 17β-Estradiol exhibited the greatest efficacy on the attenuation of obesity with the least harmful effect on skeletal muscle in a model of menopause with obesity, yet its effect on the treatment of hyperlipidemia was inferior to those of standard lipid-lowering agents. [Read the Full Post]

Addiction and the kynurenine pathway: A new dancing couple?

19 | Mar 23 2021

Nuria Morales-Puerto et al. discussed ethanol, nicotine, cannabis, amphetamines, cocaine and opioids and new prospects in the drug research field were proposed [Read the Full Post]

ALDH1A1 maintains the cancer stem-like cells properties of esophageal squamous cell carcinoma by activating the AKT signal pathway and interacting with β-catenin

17 | Mar 18 2021

Wei Wang et al. found that ALDH1A1 expression maintained the CSC properties of ESCC cells. [Read the Full Post]

Beneficial effects of elafibranor on NASH in E3L.CETP mice and differences between mice and men

24 | Mar 17 2021

Anita M van den Hoek et al. concluded that elafibranor might be particularly useful to reduce hepatic inflammation and could be a pharmacologically useful agent for human NASH, but probably in combination with other agents. [Read the Full Post]

Discovery of repurposing drug candidates for the treatment of diseases caused by pathogenic free-living amoebae

33 | Feb 25 2021

Christopher A Rice et al. demonstrated the utility of phenotypic screens for discovery of new drugs for pathogenic free-living amoebae, including Acanthamoeba for the first time. [Read the Full Post]

Priming with HDAC Inhibitors Sensitizes Ovarian Cancer Cells to Treatment with Cisplatin and HSP90 Inhibitors

20 | Feb 24 2021

Ana J Rodrigues Moita et al. found that priming with HDACi sensitized ovarian cancer cells to treatment with HSP90i or cisplatin and had an influence on the development of cisplatin resistance, both of which might contribute to an improved ovarian cancer treatment. [Read the Full Post]

Hospitalization and Mortality in Patients With Heart Failure Treated With Sacubitril/Valsartan vs. Enalapril: A Real-World, Population-Based Study

24 | Feb 12 2021

Swathi Pathadka et al. found that in real-world settings, sacubitril/valsartan was associated with improved survival and reduced heart failure-related hospitalization compared to enalapril in Asian patients with heart failure. [Read the Full Post]

Upregulation of peroxisome proliferator-activated receptor-α and the lipid metabolism pathway promotes carcinogenesis of ampullary cancer

26 | Feb 03 2021

Chih-Yang Wang et al. found that upregulation of PPARA and lipid metabolism-related genes were potential pathways in the carcinogenesis and development of ampullary cancer. [Read the Full Post]

17-DMAG dually inhibits Hsp90 and histone lysine demethylases in alveolar rhabdomyosarcoma

31 | Feb 03 2021

Shivendra Singh et al. indicated that targeting KDM in combination with chemotherapy might serve as a therapeutic approach to PAX3-FOXO1-positive aRMS. [Read the Full Post]

Population pharmacokinetic and exposure-response analyses of ivosidenib in patients with IDH1-mutant advanced hematologic malignancies

26 | Jan 30 2021

Xuemin Jiang et al. provided a framework to describe the relationship among ivosidenib dose, exposure, and clinical end points. [Read the Full Post]

Vorasidenib (AG-881): A First-in-Class, Brain-Penetrant Dual Inhibitor of Mutant IDH1 and 2 for Treatment of Glioma

31 | Jan 25 2021

Zenon Konteatis et al. described the discovery of vorasidenib (AG-881), a potent, oral, brain-penetrant dual inhibitor of both mIDH1 and mIDH2. [Read the Full Post]

MR-detectable metabolic biomarkers of response to mutant IDH inhibition in low-grade glioma

25 | Jan 25 2021

Abigail R Molloy et al. identified potential 1H- and 13C-MRS-detectable biomarkers of response to IDH1mut inhibition in gliomas. [Read the Full Post]

Regulation of cytochrome P450 4F11 expression by liver X receptor alpha

26 | Jan 21 2021

Tao Zhang et al. found that the regulation of CYP4F11 might contribute to the anti-inflammatory activity of LXRα agonists. [Read the Full Post]

Hypoxia-reoxygenation induces macrophage polarization and causes the release of exosomal miR-29a to mediate cardiomyocyte pyroptosis

26 | Jan 18 2021

Yan Wang et al. found that HR treatment induced macrophage polarization towards the M1 phenotype, which mediated CM pyroptosis through exosomal miR-29a transfer by targeting MCL-1. [Read the Full Post]

Repurposing FDA Approved Drugs as JNK3 Inhibitor for Prevention of Neuroinflammation Induced by MCAO in Rats

28 | Jan 06 2021

Zikra Zulfiqar et al. demonstrated that the novel FDA-approved medications attenuate ischemic stroke-induced neuronal degeneration, possibly by inhibiting JNK3. [Read the Full Post]

Synergistic Utilization of Necrostatin-1 and Z-VAD-FMK Efficiently Promotes the Survival of Compression-Induced Nucleus Pulposus Cells via Alleviating Mitochondrial Dysfunction

32 | Jan 03 2021

Songfeng Chen et al. found that the synergistic utilization of Necrostatin-1 and Z-VAD-FMK was a very worthwhile solution in preventing compression-mediated NP cells death, which might be largely attributed to restored mitochondrial function. [Read the Full Post]

Potent and Specific Inhibition of NTCP-Mediated HBV/HDV Infection and Substrate Transporting by a Novel, Oral-Available Cyclosporine A Analogue

28 | Dec 29 2020

Yang Liu et al. found that 27A served as a promising lead for the development of novel anti-HDV/HBV agents. [Read the Full Post]

Deciphering the Inhibition Mechanism of under Trial Hsp90 Inhibitors and Their Analogues: A Comparative Molecular Dynamics Simulation

37 | Dec 28 2020

Asma Nazar et al. suggested that under trial Hsp90 inhibitors MPC-3100 could be a potential starting point into the development of potential anticancer agents with the possibility of future directions for the improvement of early existing Hsp90 inhibitors CNF-2024 and SNX-5422 as an anticancer agent. [Read the Full Post]

Heat Shock Protein 90 Inhibitors AUY922, BIIB021 and SNX5422 Induce Bim-mediated Death of Thyroid Carcinoma Cells

27 | Dec 27 2020

Si Hyoung Kim et al. found that AUY922, BIIB021 and SNX5422 induced cytotoxicity by modulating Bim and ERK1/2, AKT and AMPK signaling in thyroid carcinoma cells. [Read the Full Post]

ScatLay: utilizing transcriptome-wide noise for identifying and visualizing differentially expressed genes

29 | Dec 24 2020

Thuy Tien Bui et al. provided a wider coverage of DE genes, and would likely pave way for finding more novel regulatory genes in future works. [Read the Full Post]

FTY720 induces ferroptosis and autophagy via PP2A/AMPK pathway in multiple myeloma cells

31 | Dec 20 2020

Yuan Zhong et al. provided a new perspective on the treatment of MM. [Read the Full Post]

HSP90 Inhibitor Ganetespib (STA-9090) Inhibits Tumor Growth in c-Myc-Dependent Esophageal Squamous Cell Carcinoma

32 | Dec 17 2020

Liuliu Guan et al. supported that the HSP90 inhibitor, STA-9090, suppressed the expression of the MYC protein and interferes with HSP90-MYC protein-protein interaction. [Read the Full Post]

Ganetespib in Combination with Pemetrexed-Platinum Chemotherapy in Patients with Pleural Mesothelioma (MESO-02): A Phase Ib Trial

30 | Dec 16 2020

Dean A Fennell et al. found that ganetespib could be combined safely with pemetrexed and platinum chemotherapy to treat patients with MPM. [Read the Full Post]

Lack of zinc finger protein 521 upregulates dopamine β-hydroxylase expression in the mouse brain, leading to abnormal behavior

30 | Dec 10 2020

Nobutaka Ohkubo et al. suggested that the lack of ZFP521 upregulated the expression of DBH, which led to a decrease in the DA level and an increase in the NA level in the brain, resulting in abnormal behaviors. [Read the Full Post]

LGR5 induces β activation and augments tumor progression by activating STAT3 in human intrahepatic cholangiocarcinoma

51 | Dec 04 2020

Keishi Kawasaki et al. thought that LGR5 was an excellent prognostic predictor and a promising therapeutic target for ICC. [Read the Full Post]

Component of nicotine-induced intracellular calcium elevation mediated through α3- and α5-containing nicotinic acetylcholine receptors are regulated by cyclic AMP in SH-SY 5Y cells

31 | Dec 03 2020

Tamayo Takahashi et al. suggested that α3 * and α5 * nAChR-mediated Ca2+ influx was possibly regulated by cAMP at the transcriptional level. [Read the Full Post]

RIP3 dependent NLRP3 inflammasome activation is implicated in acute lung injury in mice

37 | Nov 18 2020

Jingxian Chen et al. showed that RIP3 participated in the NLRP3 inflammasome activation in infiltrating macrophages in ALI induced by LPS. [Read the Full Post]

Notoginseng Leaf Triterpenes Ameliorates OGD/R-Induced Neuronal Injury via SIRT1/2/3-Foxo3a-MnSOD/PGC-1 α Signaling Pathways Mediated by the NAMPT-NAD Pathway

45 | Nov 07 2020

Weijie Xie et al. found that PNGL, as a new drug candidate, had a pivotal role in mitochondrial homeostasis and energy metabolism therapy via NAMPT against OGD-induced SH-SY5Y cell injury. [Read the Full Post]

Dehydrodiconiferyl alcohol, a lignan from Herpetospermum pedunculosum, alleviates cholestasis by activating pathways associated with the farnesoid X receptor

37 | Nov 07 2020

Xiaodong Wei et al. thought that DA might represent an effective agonist for FXR had significant therapeutic potential for the treatment of cholestatic liver injury. [Read the Full Post]

Pre-B cell colony enhancing factor induces Nampt-dependent translocation of the insulin receptor out of lipid microdomains in A549 lung epithelial cells

0 | Nov 06 2020

Qianyi Peng et al. concluded that PBEF could inhibit insulin signaling through the IR by Nampt-dependent promotion of IR translocation into the nonraft domains of A549 epithelial cells. [Read the Full Post]

VDAC upregulation and αTAT1‑mediated α‑tubulin acetylation contribute to tanespimycin‑induced apoptosis in Calu‑1 cells

47 | Nov 02 2020

Qilin Wang et al. provided evidence for the use of a combination of drugs that target VDAC1 and tubulin to induce tumour cell apoptosis. [Read the Full Post]

Identification of Subtype-Specific Metastasis-Related Genetic Signatures in Sarcoma

49 | Nov 02 2020

Ya-Ling Li et al. provided new insights into the pathogenesis, diagnosis, treatment, and prognosis of sarcomas and provided new directions for further study of sarcoma. [Read the Full Post]

Hsp90 Inhibitor; NVP-AUY922 in Combination with Doxorubicin Induces Apoptosis and Downregulates VEGF in MCF-7 Breast Cancer Cell Line

48 | Oct 16 2020

Mahshid Mohammadian et al. indicated an effective action of NVP-AUY922 in combined with DOX in this cell line. [Read the Full Post]

Heat Shock Protein 90 (Hsp90)-Inhibitor-Luminespib-Loaded-Protein-Based Nanoformulation for Cancer Therapy

50 | Oct 15 2020

Ankit K Rochani et al.suggested that DNP-based aqueous nanoformulations could be used in both pancreatic (MIA PaCa-2) and breast (MCF-7) cancer therapy. [Read the Full Post]

Myeloid deletion and therapeutic activation of AMPK do not alter atherosclerosis in male or female mice

54 | Oct 02 2020

Nicholas D LeBlond et al. suggested that intervention with the first-generation AMPK activator A-769662 was not able to stem the progression of atherosclerosis. [Read the Full Post]

Tipifarnib as a Precision Therapy for HRAS-Mutant Head and Neck Squamous Cell Carcinomas

57 | Sep 24 2020

Mara Gilardi et al. supported that HRAS represented a druggable oncogene in HNSCC through FTase inhibition by tipifarnib, thereby identifying a precision therapeutic option for HNSCCs harboring HRAS mutations. [Read the Full Post]

Clinical Significance of Program Death Ligand-1 and Indoleamine-2,3-Dioxygenase Expression in Colorectal Carcinoma

57 | Sep 17 2020

Sean Hacking et al. supported the theoretical foundation for targeting PD-L1 and IDO-1 in CRC, which now needed verification in well-designed robust clinical trials. [Read the Full Post]

Peptide vaccination directed against IDO1-expressing immune cells elicits CD8 + and CD4 + T-cell-mediated antitumor immunity and enhanced anti-PD1 responses

55 | Sep 17 2020

Souvik Dey et al. found that the in vivo antitumor effects demonstrated with IDO1-based vaccines via targeting of the tumor microenvironment highlighted the utility of mouse models for further exploration and refinement of this novel vaccine-based approach to IDO1-directed cancer therapy and its potential to improve patient response rates to anti-PD1 therapy. [Read the Full Post]

Bucladesine Attenuates Spatial Learning and Hippocampal Mitochondrial Impairments Induced by 3, 4-Methylenedioxymethamphetamine (MDMA)

66 | Aug 31 2020

Ghorban Taghizadeh et al. highlighted the role of cAMP/PKA signaling in MDMA-induced memory and mitochondrial defects. [Read the Full Post]

Protein Kinase CK2 in Cancer Energetics

85 | Aug 27 2020

Eduardo Silva-Pavez et al. proposed that the specific inhibition of CK2 might lead to a catastrophic death of cancer cells, which could become a feasible therapeutic strategy to beat this devastating disease. [Read the Full Post]

Casein kinase 2 inhibitor CX-4945 elicits an anti-Warburg effects through the downregulation of TAp73 and inhibits gastric tumorigenesis

79 | Aug 27 2020

Shengli Tang et al. suggested that CX-4945 elicited an anti-Warburg effects in gastric cancer overexpressing Tap73 and inhibited gastric tumorigenesis. [Read the Full Post]

MicroRNA-182 exacerbates blood-brain barrier (BBB) disruption by downregulating the mTOR/FOXO1 pathway in cerebral ischemia

71 | Aug 24 2020

Tongshuai Zhang et al. found that miR-182 might be a potential target for the treatment of BBB disruption during cerebral ischemia. [Read the Full Post]

Alcohol-induced CYP2E1, Mitochondrial Dynamics and Retrograde Signaling in Human Hepatic 3D Organoids

116 | Aug 03 2020

Rajesh Angireddy et al. presented a mechanistic link between CYP2E1 function and alcohol mediated mitochondrial dysfunction, retrograde signaling, and activation of hepatic steatosis in a 3D organoid system that closely recapitulated the in vivo liver response. [Read the Full Post]

Disrupting Phosphatase SHP2 in Macrophages Protects Mice From High-Fat Diet-Induced Hepatic Steatosis and Insulin Resistance by Elevating IL-18 Levels

94 | Jun 23 2020

Wen Liu et al. concluded that pharmacological inhibition of SHP2 might represent a possible therapeutic strategy for the management of type 2 diabetes. [Read the Full Post]

Effects of the PI3K/Akt Signaling Pathway on the Apoptosis of Early Host Cells Infected With Eimeria Tenella

207 | Jun 21 2020

Xuesong Zhang et al. investigated the role of PI3K/Akt signaling pathway on host cell apoptosis in the early infection of Eimeria tenella,the early development of E. tenella could inhibit host cell apoptosis by downregulating the Caspase-3 activity. [Read the Full Post]

Evaluation of Musculoskeletal Phenotype of the G608G Progeria Mouse Model With Lonafarnib, Pravastatin, and Zoledronic Acid as Treatment Groups

98 | Jun 10 2020

Maria B Cubria et al. characterized the musculoskeletal phenotype of the homozygous G608G BAC-transgenic progeria mouse model, and determined the phenotype changes of HGPS mice after a five-arm preclinical trial of different treatment combinations with lonafarnib, pravastatin, and zoledronic acid. [Read the Full Post]

TGF-β1-mediated Repression of SLC7A11 Drives Vulnerability to GPX4 Inhibition in Hepatocellular Carcinoma Cells

119 | Jun 09 2020

Do Hyung Kim et al. showed that TGF-β1 repressed xCT expression via Smad3 activation and enhanced lipid peroxidation in hepatocellular carcinoma cells with an early TGF-β1 signature, which would benefit from the targeting of GPX4. [Read the Full Post]

Effects of nanoparticle-mediated delivery of pitavastatin on atherosclerotic plaques in ApoE-knockout mice and THP-1-derived macrophages

119 | May 05 2020

Sun Y et al. demonstrated that pitavastatin-NP administration was more effective in attenuating the development of atherosclerotic plaques compared with systemic administration of pitavastatin. [Read the Full Post]

A Phase I Study of PF-04929113 (SNX-5422), an Orally Bioavailable Heat Shock Protein 90 Inhibitor, in Patients With Refractory Solid Tumor Malignancies and Lymphomas

184 | Apr 19 2020

Arun Rajan et al. showed that PF-04929113 administered orally twice a week is well tolerated and inhibits its intended target Hsp90. No objective responses were seen, but long-lasting stabilizations were obtained. Although no clinically significant drug-related ocular toxicity was seen in this study, the development of PF-04929113 has been discontinued because of ocular toxicity seen in animal models and in a separate phase I study. [Read the Full Post]

SNX-2112, a Selective Hsp90 Inhibitor, Potently Inhibits Tumor Cell Growth, Angiogenesis, and Osteoclastogenesis in Multiple Myeloma and Other Hematologic Tumors by Abrogating Signaling via Akt and ERK

197 | Apr 19 2020

Yutaka Okawa et al. provided the framework for clinical studies of SNX-2112 to improve patient outcome in MM and other hematologic malignancies. [Read the Full Post]

Identifying off-target effects of etomoxir reveals that carnitine palmitoyltransferase I is essential for cancer cell proliferation independent of β-oxidation

163 | Apr 12 2020

Yao CH et al. suggested that transport of at least some long-chain fatty acids into the mitochondria by CPT1 may be required for anabolic processes that support healthy mitochondrial function and cancer cell proliferation independent of FAO. [Read the Full Post]

LB-100, a novel Protein Phosphatase 2A (PP2A) inhibitor, sensitizes malignant meningioma cells to the therapeutic effects of radiation

157 | Mar 19 2020

Ho WS et al. provided convincing preclinical data to support the use of LB-100 as a radiosensitizing agent for treatment of malignant meningioma. Its potential for clinical application deserves further investigation. [Read the Full Post]

Ganetespib limits ciliation and cystogenesis in autosomal-dominant polycystic kidney disease (ADPKD)

253 | Mar 15 2020

Nikonova AS et al. identified a new biologic activity for HSP90 and support a cilia-based mechanism for cyst repression.-Nikonova, A. S., Deneka, A. Y., Kiseleva, A. A., Korobeynikov, V., Gaponova, A., Serebriiskii, I. G., Kopp, M. C., Hensley, H. H., Seeger-Nukpezah, T. N., Somlo, S., Proia, D. A., Golemis, E. A. Ganetespib limits ciliation and cystogenesis in autosomal-dominant polycystic kidney disease (ADPKD). [Read the Full Post]

The novel HSP90 inhibitor STA-9090 exhibits activity against Kit-dependent and -independent malignant mast cell tumors

239 | Mar 15 2020

Lin TY et al. showed that STA-9090 exhibits broad activity against mast cells expressing WT or mutant Kit, suggesting it may be an effective agent in the clinical setting against mast cell malignancies. [Read the Full Post]

mbined use of metformin and atorvastatin attenuates atherosclerosis in rabbits fed a high-cholesterol diet

174 | Mar 13 2020

Luo F et al. suggested that atorvastatin/metformin combination therapy may achieve additional anti-atherosclerotic benefits likely through increasing cholesterol efflux in macrophages. [Read the Full Post]

The Role and Mechanism of CRT0066101 as an Effective Drug for Treatment of Triple-Negative Breast Cancer

213 | Mar 09 2020

Liu Y et al. indicated that PRKD inhibitor CRT0066101 exhibits anti-TNBC effects via modulating a phosphor-signaling network and inhibiting the phosphorylation of many cancer-driving factors, including MYC, MAPK1/3, AKT, YAP, and CDC2, providing insight into the important roles as well as the molecular mechanism of CRT0066101 as an effective drug for TNBC. [Read the Full Post]

Evaluation of the dopamine β-hydroxylase (DβH) inhibitor nepicastat in participants who meet criteria for cocaine use disorder

203 | Mar 04 2020

De La Garza R 2nd et al. indicated that nepicastat is safe when co-administered with cocaine and may suppress its positive subjective effects, and may be viable as a pharmacotherapy for treatment of cocaine use disorder. [Read the Full Post]

RIP3 inhibition protects locomotion function through ameliorating mitochondrial antioxidative capacity after spinal cord injury

0 | Feb 13 2020

Wang Y et al. suggested improving antioxidative capacity as a potential multifunctional treatment after SCI and the broader possibility of targeting RIP3 activity as a therapeutic window for spinal neuroprotective intervention. [Read the Full Post]

MYC promotes tryptophan uptake and metabolism by the kynurenine pathway in colon cancer

215 | Jan 17 2020

Venkateswaran N et al. proposed that limiting cellular kynurenine or its downstream targets could present a new strategy to reduce the proliferation of MYC-dependent cancer cells. [Read the Full Post]

Farnesoid X receptor agonist GW4064 ameliorates lipopolysaccharide-induced ileocolitis through TLR4/MyD88 pathway related mitochondrial dysfunction in mice

140 | Jan 15 2020

Liu HM et al. demonstrated that central roles of FXR in coordinating regulation of both inflammation and mitochondrial dysfunction. We propose that GW4064 is promising therapeutic agent for treatment of ileocolitis. [Read the Full Post]

Selective Cytotoxicity of the NAMPT Inhibitor FK866 Toward Gastric Cancer Cells With Markers of the Epithelial-Mesenchymal Transition, Due to Loss of NAPRT

149 | Jan 14 2020

Lee J et al. showed that FK866 selectively kills gastric cancer cells with an EMT gene expression signature by inhibiting nicotinamide phosphoribosyltransferase in cells with NAPRT deficiency. Loss of NAPRT expression, frequently through promoter hypermethylation, is observed in many gastric tumors of the EMT subtype. FK866 might be used to treat patients with tumors of this subtype. [Read the Full Post]

Nicotinamide Phosphoribosyltransferase Inhibitor APO866 Prevents IL-1β-Induced Human Nucleus Pulposus Cell Degeneration via Autophagy

249 | Jan 14 2020

Shi C et al. indicated that APO866 protects NP cells and induces autophagy by inhibiting IL-1β-induced NP cell degeneration and apoptosis, which may have therapeutic potential in IDD. [Read the Full Post]

Pre-B cell colony enhancing factor induces Nampt-dependent translocation of the insulin receptor out of lipid microdomains in A549 lung epithelial cells

0 | Jan 13 2020

Peng Q et al. concluded that PBEF can inhibit insulin signaling through the IR by Nampt-dependent promotion of IR translocation into the nonraft domains of A549 epithelial cells. PBEF-induced alterations in the spatial geometry of the IR provide a mechanistic explanation for insulin resistance in inflammatory states associated with upregulation of PBEF. [Read the Full Post]

17-AAG inhibits vemurafenib-associated MAP kinase activation and is synergistic with cellular immunotherapy in a murine melanoma model

301 | Jan 08 2020

Joshi SS et al. indicated their sdudies support a role for 17-AAG and HSP90 inhibition in enhancing cellular immunotherapy for melanoma. [Read the Full Post]

Tanespimycin as antitumor therapy

0 | Jan 07 2020

Dimopoulos MA et al. indiacated that tanespimycin represents a promising new agent for the treatment of relapsed/refractory MM. Results of ongoing and future trials will determine the role of tanespimycin both in MM and other malignancies, including breast cancer. [Read the Full Post]

Hsp90 inhibitors induce the unfolded protein response in bovine and mice lung cells

273 | Dec 19 2019

Kubra KT et al. demonstrated that Hsp90 inhibition triggers the activities of the unfolded protein response, and suggests that this molecular machinery contributes in the protective action of Hsp90 inhibitors in the lung microvasculature. [Read the Full Post]

NVP-AUY922, a novel HSP90 inhibitor, inhibits the progression of malignant pheochromocytoma in vitro and in vivo

0 | Dec 19 2019

Lian J et al. indicated that NVP-AUY922 exhibits potent anti-PCC activities in vitro and in vivo and represents a promising therapeutic small molecule for treating malignant PCC. [Read the Full Post]

Activity of the Hsp90 inhibitor luminespib among non-small-cell lung cancers harboring EGFR exon 20 insertions

257 | Dec 18 2019

Piotrowska Z et al.showed that this study met its primary end point, suggesting that luminespib may be an active therapy for advanced NSCLC patients with EGFR ins20. Luminespib is generally well-tolerated, though reversible low-grade ocular toxicity is common. Further study of luminespib and other hsp90 inhibitors in this population is warranted. [Read the Full Post]

Effect of A-769662, a direct AMPK activator, on Tlr-4 expression and activity in mice heart tissue

248 | Dec 09 2019

Rameshrad M et al. demonstrated that activation of AMPK, by A-769662 agent, could inhibit Tlr-4 expression and activity, suggesting a link between AMPK and Tlr-4 in heart tissue. [Read the Full Post]

Tipifarnib prevents development of hypoxia-induced pulmonary hypertension

0 | Dec 02 2019

Duluc L et al. demonstrated the importance of protein farnesylation in pulmonary vascular remodelling and provides a rationale for selective targeting of this pathway in pulmonary hypertension. [Read the Full Post]

First-in-Human Phase I Study of the Oral Inhibitor of Indoleamine 2,3-Dioxygenase-1 Epacadostat (INCB024360) in Patients with Advanced Solid Malignancies

213 | Nov 25 2019

Beatty GL et al. showed that epacadostat was generally well tolerated, effectively normalized kynurenine levels, and produced maximal inhibition of IDO1 activity at doses of ≥100 mg BID. Studies investigating epacadostat in combination with other immunomodulatory drugs are ongoing. [Read the Full Post]

Updates in the Clinical Development of Epacadostat and Other Indoleamine 2,3-Dioxygenase 1 Inhibitors (IDO1) for Human Cancers

221 | Nov 24 2019

Komiya T et al. indicated that IDO1 is a promising target that can improve the treatment outcome in the field of Immuno-oncology. Several orally available IDO1 inhibitors including Epacadostat have entered human clinical trials over the last few years without a major safety concern. Although there is no objective response in single-agent trials, combination regimens with PD-1 inhibitors appear to exceed the activity of PD-1 inhibitors alone. Recent phase III ECHO 301 trial testing the combination of Epacadostat with Pembrolizumab in melanoma did not show superior outcome compared to Pembrolizumab alone. This lead to halting of other phase III trials using IDO1 inhibitors. In this minireview, we will discuss the recent clinical development of Epacadostat and other IDO1 inhibitors. [Read the Full Post]

CX-4945: the protein kinase CK2 inhibitor and anti-cancer drug shows anti-fungal activity

246 | Nov 07 2019

Masłyk M et al. indicated their data unveil the dual-activity of CX-4945; when used in anti-cancer therapy, it may simultaneously prevent cancer-associated candidiasis. [Read the Full Post]

FoxO1 regulates myocardial glucose oxidation rates via transcriptional control of pyruvate dehydrogenase kinase 4 expression

177 | Nov 02 2019

Gopal K et al. demonstrated that pyruvate dehydrogenase kinase 4 is a direct transcriptional target of FoxO1 (but not FoxO3/FoxO4) in the heart. Furthermore, we report here, for the first time, that FoxO1 inhibition increases glucose oxidation in the isolated working mouse heart. [Read the Full Post]

Optimizing lonafarnib treatment for the management of chronic delta hepatitis: The LOWR HDV-1 study

208 | Sep 05 2019

Yurdaydin C et al. showed the cytochrome P450 3A4 inhibitor, RTV, allows a lower LNF dose to be used while achieving higher levels of postabsorption LNF, yielding better antiviral responses and tolerability. In addition, combining LNF with PEG-IFNα achieved more substantial and rapid HDV-RNA reduction, compared to historical responses with PEG-IFNα alone. Twelve weeks of LNF can result in posttreatment HDV-RNA negativity in some patients, which we speculate results from restoring favorable immune responses. These results support further development of LNF with RTV boosting and exploration of the combination of LNF with PEG-IFN. [Read the Full Post]

Allosteric inhibition of SHP2 phosphatase inhibits cancers driven by receptor tyrosine kinases

0 | Aug 19 2019

Chen YN et al. demonstrated that pharmacological inhibition of SHP2 is a valid therapeutic approach for the treatment of cancers. [Read the Full Post]

Allosteric inhibition of SHP2 phosphatase inhibits cancers driven by receptor tyrosine kinases

253 | Aug 09 2019

Chen YN et al. demonstrated that pharmacological inhibition of SHP2 is a valid therapeutic approach for the treatment of cancers. [Read the Full Post]

Irisin Is Controlled by Farnesoid X Receptor and Regulates Cholesterol Homeostasis

249 | Jun 17 2019

Li H et al. showed taht activation of FXR induces FNDC5 mRNA expression in human and increased the circulating level of Irisin in Rhesus macaques. FNDC5/Irisin is a direct transcriptional target of FXR. Irisin may be a novel therapeutic strategy for dyslipidemia and atherosclerosis. [Read the Full Post]

RIP3 inhibition protects locomotion function through ameliorating mitochondrial antioxidative capacity after spinal cord injury

293 | Jun 17 2019

Wang Y et al. suggested improving antioxidative capacity as a potential multifunctional treatment after SCI and the broader possibility of targeting RIP3 activity as a therapeutic window for spinal neuroprotective intervention. [Read the Full Post]

Lonafarnib synergizes with azoles against Aspergillus spp. and Exophiala spp

212 | Jun 13 2019

Qiao J et al. demonstrated that lonafarnib could enhance the in vitro antifungal activity of itraconazole, posaconazole and voriconazole against Aspergillus spp. and E. dermatitidis, suggesting that azoles, especially itraconazole and posaconazole, combined with farnesyltransferase inhibitor might provide a potential strategy to the management of Aspergillus and Exophiala infections. However, further studies are warranted to elucidate the underlying mechanism and to investigate the potential of reliable and safe application in clinical practice. [Read the Full Post]

CX-4945, a Selective Inhibitor of Casein Kinase 2, Synergizes with B Cell Receptor Signaling Inhibitors in Inducing Diffuse Large B Cell Lymphoma Cell Death

365 | Jun 08 2019

Mandato E et al. suggested a role for CK2 downstream of the BCR in controlling survival pathways crucial for cell growth of different DLBCL subtypes. Also, the use of CX-4945 in combination with BCR signaling blockers could represent a novel rational therapeutic approach in the DLBCL. [Read the Full Post]

Targeting FoxO1 with AS1842856 suppresses adipogenesis

240 | Jun 02 2019

Zou P et al. suggested AS1842856 can be an anti-obesity agent that warrants further investigation. [Read the Full Post]

NVP-AUY922, a novel HSP90 inhibitor, inhibits the progression of malignant pheochromocytoma in vitro and in vivo

469 | May 31 2019

Lian J et al. showed that NVP-AUY922 exhibits potent anti-PCC activities in vitro and in vivo and represents a promising therapeutic small molecule for treating malignant PCC. [Read the Full Post]

Quantitative phosphoproteomic analysis of acquired cancer drug resistance to pazopanib and dasatinib

422 | May 26 2019

Vyse S et al. provided a useful resource detailing the candidate signalling determinants of acquired TKI resistance; and reveals a therapeutic approach of inhibiting HSP90 function as a means of salvage therapy to overcome pazopanib and dasatinib resistance. [Read the Full Post]

AMP-activated protein kinase (AMPK) activator A-769662 increases intracellular calcium and ATP release from astrocytes in an AMPK-independent manner

429 | May 23 2019

Vlachaki Walker JM et al. indicated that AMPK is required to maintain basal eATP levels but is not required for A-769662-induced increases in eATP. A-769662 (>50 μM) enhanced intracellular calcium levels leading to ATP release in an AMPK and purinergic receptor independent pathway. [Read the Full Post]

Tipifarnib prevents development of hypoxia-induced pulmonary hypertension

255 | May 22 2019

Duluc L et al. demonstrated the importance of protein farnesylation in pulmonary vascular remodelling and provides a rationale for selective targeting of this pathway in pulmonary hypertension. [Read the Full Post]

Effects of EF-24, RAD001, and paclitaxel on the expression profiles of apoptotic and anti-apoptotic genes

429 | May 15 2019

Alp E et al. showed that response of these cells to paclitaxel, EF-24, and RAD001 was found different at the transcriptional level of apoptotic and antiapoptotic genes. [Read the Full Post]

Effects of Epacadostat on Brain Extracellular Fluid Concentrations of Serotonin -- An Intracerebral Microdialysis Study in Sprague-Dawley Rats

364 | May 14 2019

Zhang Y et al. suggested that serotonin syndrome is unlikely following treatment with either epacadostat alone or with combination with MAOIs such as linezolid. [Read the Full Post]

Drug sensitivity profiling identifies potential therapies for lymphoproliferative disorders with overactive JAK/STAT3 signaling

475 | May 06 2019

Kuusanmäki H et al. showed alternative approaches to inhibit STAT3 activity and suggest Hsp90 as a therapeutic target in lymphoproliferative disorders with constitutively active STAT3. [Read the Full Post]

Superior anti-tumor activity of the MDM2 antagonist idasanutlin and the Bcl-2 inhibitor venetoclax in p53 wild-type acute myeloid leukemia models

0 | May 04 2019

Lehmann C et al. provided functional and molecular insight on the superior anti-tumor activity of combined idasanutlin and venetoclax treatment in AML and support its further exploration in clinical studies. [Read the Full Post]

Nicotinamide phosphoribosyltransferase inhibitor APO866 induces C6 glioblastoma cell death via autophagy

275 | Apr 23 2019

Yang P et al indicated that APO866 induced pro-death autophagy in C6 glioblastoma cells by decreasing intracellular NAD, and low concentration of APO866 can be used as an autophagy inducer in autophagic-death sensitive glioblastoma. [Read the Full Post]

FK866-induced NAMPT inhibition activates AMPK and downregulates mTOR signaling in hepatocarcinoma cells

251 | Apr 22 2019

Schuster S et al. revealed an important role of the NAMPT-mediated NAD salvage pathway in the energy homeostasis of hepatocarcinoma cells and suggest NAMPT inhibition as a potential treatment option for HCC. [Read the Full Post]

Pre-B cell colony enhancing factor induces Nampt-dependent translocation of the insulin receptor out of lipid microdomains in A549 lung epithelial cells

281 | Apr 15 2019

Peng Q et al. concluded that PBEF can inhibit insulin signaling through the IR by Nampt-dependent promotion of IR translocation into the nonraft domains of A549 epithelial cells. PBEF-induced alterations in the spatial geometry of the IR provide a mechanistic explanation for insulin resistance in inflammatory states associated with upregulation of PBEF. [Read the Full Post]

CK2 inhibition with silmitasertib promotes methuosis-like cell death associated to catastrophic massive vacuolization of colorectal cancer cells

394 | Apr 13 2019

Silva-Pavez E et al. suggested that an aberrantly elevated expression/activity of CK2 may play a key role in CRC, promoting cell viability and proliferation in untreated cells, however, its inhibition with silmitasertib promotes methuosis-like cell death associated to massive catastrophic vacuolization, accounting for decreased tumorigenicity at later times. These characteristics of silmitasertib support a potential therapeutic use in CRC patients and probably other CK2-dependent cancers. [Read the Full Post]

Clinical evaluation of laboratory methods to monitor exposure of rivaroxaban at trough and peak in patients with atrial fibrillation

254 | Mar 15 2019

Al-Aieshy F et al. found that the POC assay for PT-INR could be useful to indicate high exposure to rivaroxaban in emergency situations although further validation is required. [Read the Full Post]

Tanespimycin as antitumor therapy

630 | Feb 24 2019

Dimopoulos MA et al. showed that tanespimycin represents a promising new agent for the treatment of relapsed/refractory MM. Results of ongoing and future trials will determine the role of tanespimycin both in MM and other malignancies, including breast cancer. [Read the Full Post]

Effects of cancer-associated point mutations on the structure, function, and stability of succinate dehydrogenase A

558 | Feb 22 2019

Cao ZF et al. provided information important for understanding the molecular mechanisms of SDHA mutations in tumors. [Read the Full Post]

The Phosphodiesterase 10A Inhibitor PF-2545920 Enhances Hippocampal Excitability and Seizure Activity Involving the Upregulation of GluA1 and NR2A in Post-synaptic Densities

279 | Feb 15 2019

Zhang Y et al. suggested it would be detrimental to use the drug in seizure patients and might cause neuronal hyperexcitability in non-epileptic individuals. [Read the Full Post]

Upregulation of hydroxysteroid sulfotransferase 2B1b promotes hepatic oval cell proliferation by modulating oxysterol-induced LXR activation in a mouse model of liver injury

0 | Feb 12 2019

Wang Z et al. indicated that upregulation of SULT2B1b might promote HOC proliferation and aggravate liver injury via the suppression of oxysterol-induced LXR activation in chemically induced mouse liver injury. [Read the Full Post]

In vivo activation of invariant natural killer T cells induces systemic and local alterations in T-cell subsets prior to preterm birth

300 | Feb 11 2019

Gomez-Lopez N et al. found that iNKT-cell activation altered the systemic and local T-cell subsets prior to preterm labour/birth; however, treatment with rosiglitazone partially reversed such effects. [Read the Full Post]

Targeting the epigenome: Screening bioactive compounds that regulate histone deacetylase activity

0 | Jan 30 2019

Godoy LD et al. provided the first step in identifying multiple bioactive compound HDAC inhibitors. [Read the Full Post]

Sildenafil suppresses the proliferation and enhances the apoptosis of hemangioma endothelial cells

261 | Jan 13 2019

He X et al. indicated the present study concluded that PDE-5 may be a potential therapeutic target for hemangiomas and Id-1 may serve a vital role in the associated signaling transduction pathways. [Read the Full Post]

Inhibition of related JAK/STAT pathways with molecular targeted drugs shows strong synergy with ruxolitinib in chronic myeloproliferative neoplasm

618 | Jan 08 2019

Barrio S et al. showed the combination of ruxolitinib with inhibitors that target these pathways has a strong synergistic effect, which may be due to decreased activation of the common effector, STAT5. [Read the Full Post]

Low-Dose Farnesyltransferase Inhibitor Suppresses HIF-1α and Snail Expression in Triple-Negative Breast Cancer MDA-MB-231 Cells In Vitro

297 | Jan 05 2019

Tanaka T et al. suggested that FTIs may be capable of ameliorating the aggressive phenotype of TNBC by suppressing the HIF-1α-Snail pathway. [Read the Full Post]

Inhibition of the Pentose-phosphate Pathway Selectively Sensitizes Leukemia Lymphocytes to Chemotherapeutics by ROS-independent Mechanism

0 | Jan 05 2019

Zhelev Z et al. suggested that 6-ANA could be used as a supplementary component in anticancer chemotherapy, and would allows therapeutic doses of anticancer drugs to be reduced, thereby minimizing their side-effects. [Read the Full Post]

Synergistic Cytotoxicity of Melatonin and New-generation Anticancer Drugs Against Leukemia Lymphocytes But Not Normal Lymphocytes

0 | Jan 04 2019

Zhelev Z et al. suggested that melatonin is a promising supplementary component in chemotherapy which allows the therapeutic doses of anticancer drugs to be reduced, minimizing their side-effects. [Read the Full Post]

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

0 | Jan 03 2019

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

PPARβ/δ, a Novel Regulator for Vascular Smooth Muscle Cells Phenotypic Modulation and Vascular Remodeling after Subarachnoid Hemorrhage in Rats

712 | Dec 27 2018

Zhang H et al. identified PPARβ/δ as a useful regulator for VSMC phenotypic switch and vascular remodeling following SAH, providing novel insights into the therapeutic strategies of delayed cerebral ischemia. [Read the Full Post]

The antibiotic polymyxin B exhibits novel antifungal activity against Fusarium species

0 | Dec 23 2018

Hsu LH et al. found that PMB was fungicidal against all 12 Fusarium strains, with minimum fungicidal concentrations of 32 µg/mL or 64 µg/mL for most strains tested, as evidenced by broth dilution, methylene blue staining and XTT reduction assays. PMB can reduce the germination rates of conidia, but not chlamydospores, and can cause defects in cell membrane integrity in Fusarium strains. [Read the Full Post]

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

0 | Dec 21 2018

Lee S et al. revealed that CCN1-GFs treated with sclareol showed decreased levels of UVB-induced CCN1 expression. [Read the Full Post]

Microengineered cultures containing human hepatic stellate cells and hepatocytes for drug development

336 | Dec 16 2018

Davidson MD et al. found that NADPH oxidase (NOX) inhibition and farnesoid X receptor (FXR) activation using clinically relevant drugs alleviated hepatic dysfunctions in MPTCs. In conclusion, MPTCs recapitulate symptoms of NASH- and early fibrosis-like dysfunctions in PHHs and have utility for drug discovery in this space. [Read the Full Post]

FAM83A is amplified and promotes cancer stem cell-like traits and chemoresistance in pancreatic cancer

614 | Dec 15 2018

Chen S et al. indicated that FAM83A has a vital oncogenic role to promote pancreatic cancer progression and may represent a potential clinical target. [Read the Full Post]

PPARβ/δ activation protects against corticosterone-induced ER stress in astrocytes by inhibiting the CpG hypermethylation of microRNA-181a

672 | Dec 10 2018

Ji J et al. suggested that PPARβ/δ activation in astrocytes might be a promising target for regulating ER stress-induced astrocytic injury. [Read the Full Post]

A sensitive virus yield assay for evaluation of Antivirals against Zika Virus

0 | Nov 26 2018

Goebel S et al. indicated that due to reproducible assay performance, qPCR associated higher sensitivity and short duration of the assay time, this novel cell based assay will be very useful for confirming the activity of antivirals against ZIKV. [Read the Full Post]

Loss-of-function screens of druggable targetome against cancer stem-like cells

0 | Nov 24 2018

SiRNAs that selectively reduced CSLC only were found to target genes for cholesterol and unsaturated fatty acid synthesis. [Read the Full Post]

N-3 polyunsaturated fatty acids increase hepatic fibroblast growth factor 21 sensitivity via a PPAR-γ-β-klotho pathway

0 | Nov 15 2018

Yang W et al. indicated n-3 PUFAs increase hepatic FGF21 sensitivity and β-klotho expression probably through a PPAR-γ-dependent mechanism, and may thereby exert hepatic beneficial effects on lipid metabolism. [Read the Full Post]

Identification of the Serine Biosynthesis Pathway as a Critical Component of BRAF Inhibitor Resistance of Melanoma, Pancreatic, and Non-Small Cell Lung Cancer Cells

374 | Nov 08 2018

The novel aspects of this study are the direct identification of serine biosynthesis as a critical mechanism of BRAF V600E inhibitor resistance and the first successful example of using gemcitabine + BRAFis in combination to kill previously drug-resistant cancer cells, creating the translational potential of pretreatment with gemcitabine prior to BRAFi treatment of tumor cells to reverse resistance within the mutational profile and the WT. [Read the Full Post]

Btk inhibition treats TLR7/IFN driven murine lupus

423 | Oct 23 2018

Bender AT et al. provided translational insight into how Btk inhibition may provide benefit to a variety of SLE patients by affecting both BCR and FcR signaling. [Read the Full Post]

A sensitive virus yield assay for evaluation of Antivirals against Zika Virus

516 | Oct 15 2018

Goebel S et al. showed qPCR associated higher sensitivity and short duration of the assay time, this novel cell based assay will be very useful for confirming the activity of antivirals against ZIKV. [Read the Full Post]

A multi-targeted liquid chromatography-mass spectrometry screening procedure for the detection in human urine of drugs non-prohibited in sport commonly used by the athletes

530 | Oct 09 2018

Mazzarino M et al. indicated this work presents an analytical method for the simultaneous analysis in human urine of 38 pharmacologically active compounds (19 benzodiazepine-like substances, 7 selective serotonin reuptake inhibitors, 4 azole antifungal drugs, 5 inhibitors of the phosphodiesterases type 4 and 3 inhibitors of the phosphodiesterase type 5) by liquid-chromatography coupled with tandem mass spectrometry. [Read the Full Post]

The phosphodiesterase 4 inhibitor roflumilast augments the Th17-promoting capability of dendritic cells by enhancing IL-23 production, and impairs their T cell stimulatory activity due to elevated IL-10

357 | Oct 08 2018

Bros M et al. suggested that PDE4 inhibitors aside from their broad overall anti-inflammatory effects may enhance the Th17-polarizing capacity in DCs as an unwanted side effect. [Read the Full Post]

Synergistic cytotoxicity of BIIB021 with triptolide through suppression of PI3K/Akt/mTOR and NF-κB signal pathways in thyroid carcinoma cells

1999 | Oct 07 2018

Kim SH et al. suggested that BIIB021 has a cytotoxic activity accompanied by regulation of hsp90 client proteins in thyroid carcinoma cells. Moreover, the synergism between BIIB021 and triptolide in induction of cytotoxicity is associated with the inhibition of PI3K/Akt/mTOR and NF-κB signal pathways, the underexpression of survivin and the activation of DNA damage response in thyroid carcinoma cells. [Read the Full Post]

Targeting the epigenome: Screening bioactive compounds that regulate histone deacetylase activity

510 | Sep 26 2018

Godoy LD et al. provided the first step in identifying multiple bioactive compound HDAC inhibitors. Taken together, this report sets the stage for future exploration of these bioactive compounds as epigenetic regulators to potentially ameliorate chronic disease. [Read the Full Post]

Androgen Deprivation Followed by Acute Androgen Stimulation Selectively Sensitizes AR-Positive Prostate Cancer Cells to Ionizing Radiation

504 | Sep 22 2018

Hedayati M et al. suggested a potential cooperative effect and improved tumor growth delay with androgen-induced DSBs and radiation with implications for improving the therapeutic index of prostate cancer radiation therapy. [Read the Full Post]

Short-term high-fat feeding induces islet macrophage infiltration and β-cell replication independently of insulin resistance in mice

426 | Sep 21 2018

Woodland DC et al. suggested the existence of MΦ-mediated mechanisms in β-cell replication that are independent of insulin resistance. [Read the Full Post]

Neuregulin 1-activated ERBB4 interacts with YAP to induce Hippo pathway target genes and promote cell migration

455 | Sep 21 2018

Haskins JW et al. suggested that NRG1-ERBB4-YAP signaling contributes to the aggressive behavior of tumor cells. [Read the Full Post]

Integrated analysis of transcriptomes of cancer cell lines and patient samples reveals STK11/LKB1-driven regulation of cAMP phosphodiesterase-4D

436 | Sep 20 2018

He N et al. showed that multidimensional analysis of a well-characterized large-scale panel of cancer cell lines provides unprecedented opportunities for the identification of unexpected oncogenic mechanisms and mutation-specific drug targets. [Read the Full Post]

SIRT1 prevents hyperuricemia via the PGC-1α/PPARγ-ABCG2 pathway

0 | Sep 20 2018

Wang J et al. demonstrated that SIRT1 and its activator, RSV, have clear anti-hyperuricemia functions in this mouse model. [Read the Full Post]

Kaempferol suppresses lipid accumulation by inhibiting early adipogenesis in 3T3-L1 cells and zebrafish

680 | Sep 16 2018

Lee YJ et al. indicated that kaempferol might have an anti-obesity effect by regulating lipid metabolism. [Read the Full Post]

Luteinizing Hormone Causes Phosphorylation and Activation of the cGMP Phosphodiesterase PDE5 in Rat Ovarian Follicles, Contributing, Together with PDE1 Activity, to the Resumption of Meiosis.

426 | Sep 15 2018

Egbert JR et al. showed that activities of both PDE5 and PDE1 contribute to the LH-induced resumption of meiosis in rat oocytes, and that phosphorylation and activation of PDE5 is a regulatory mechanism. [Read the Full Post]

The LXR ligand GW3965 inhibits Newcastle disease virus infection by affecting cholesterol homeostasis

459 | Sep 13 2018

Sheng XX et al. suggested that GW3965 inhibits NDV infection, probably by affecting cholesterol homeostasis. [Read the Full Post]

Resveratrol provides neuroprotection by inhibiting phosphodiesterases and regulating the cAMP/AMPK/SIRT1 pathway after stroke in rats

528 | Sep 10 2018

Wan D et al. indicated that resveratrol provides neuroprotection by inhibiting PDEs and regulating the cAMP/AMPK/SIRT1 pathway, which reduces ATP energy consumption during ischemia. [Read the Full Post]

The anti-inflammatory effects of Morin hydrate in atherosclerosis is associated with autophagy induction through cAMP signaling

450 | Sep 10 2018

Zhou Y et al. suggested that anti-AS and anti-inflammatory effects of MO are largely associated with its induction of autophagy through stimulation of cAMP-PKA-AMPK-SIRT1 signaling pathway. [Read the Full Post]

The antibiotic polymyxin B exhibits novel antifungal activity against Fusarium species

476 | Aug 31 2018

Hsu LH et al. indicated evolutionary divergence of mechanisms between yeast pathogens and the filamentous fungus Fusarium. [Read the Full Post]

A novel, rapid method to compare the therapeutic windows of oral anticoagulants using the Hill coefficient

0 | Aug 27 2018

Chang JB et al. showed a significant variation among the Hill coefficients, suggesting a similar variation in therapeutic windows among anticoagulants in our assay. [Read the Full Post]

A High Throughput Phenotypic Screening reveals compounds that counteract premature osteogenic differentiation of HGPS iPS-derived mesenchymal stem cells

510 | Aug 07 2018

Lo Cicero A et al. highlight the potential of high-throughput drug screening using HGPS iPS-derived cells, in order to find therapeutic compounds for HGPS and, potentially, for other aging-related disorders. [Read the Full Post]

ICAM-1-Targeted Liposomes Loaded with Liver X Receptor Agonists Suppress PDGF-Induced Proliferation of Vascular Smooth Muscle Cells

530 | Jul 16 2018

Huang X et al. identified anti-ICAM-T0901317 liposomes as a promising nanotherapeutic approach to overcome VSMC proliferation during atherosclerosis progression. [Read the Full Post]

Inhibiting GLUT-1 expression and PI3K/Akt signaling using apigenin improves the radiosensitivity of laryngeal carcinoma in vivo

542 | Jun 19 2018

Bao YY et al. suggested that the effects of apigenin on inhibiting xenograft growth and enhancing xenograft radiosensitivity may be associated with suppressing the expression of GLUT-1 via the PI3K/Akt pathway. In addition, apigenin may enhance the effects of GLUT-1 AS-ODNs via the same mechanism. [Read the Full Post]

N-3 polyunsaturated fatty acids increase hepatic fibroblast growth factor 21 sensitivity via a PPAR-γ-β-klotho pathway

1515 | Jun 11 2018

Yang W et al. indicated n-3 PUFAs increase hepatic FGF21 sensitivity and β-klotho expression probably through a PPAR-γ-dependent mechanism, and may thereby exert hepatic beneficial effects on lipid metabolism. [Read the Full Post]

The non-Geldanamycin Hsp90 inhibitors enhanced the antifungal activity of fluconazole

952 | Jun 09 2018

Li L et al. showed that the activity of FLC against C. albicans biofilm formation in vitro is significantly enhanced when used in combination with HSP990. [Read the Full Post]

A screening assay for the identification of host cell requirements and antiviral targets for hepatitis D virus infection

629 | Jun 08 2018

Buchmann B et al. provided a potentially useful tool to screen for substances with anti-HDV activity and novel insights into interactions between HDV replication and the human kinome. [Read the Full Post]

WIP1 modulates responsiveness to Sonic Hedgehog signaling in neuronal precursor cells and medulloblastoma

749 | Jun 02 2018

Wen J et al. suggested an important cross-talk between SHH and WIP1 pathways that accelerates tumorigenesis and supports WIP1 inhibition as a potential treatment strategy for MB. [Read the Full Post]

Androgen deprivation therapy sensitizes triple negative breast cancer cells to immune-mediated lysis through androgen receptor independent modulation of osteoprotegerin

611 | May 22 2018

Kwilas AR et al. supported the consideration of AR inhibition therapy for the treatment of AR- TNBC, especially in combination with cancer immunotherapy, providing a potential novel therapeutic option for select patients. [Read the Full Post]

Resveratrol Attenuates Aβ25-35 Caused Neurotoxicity by Inducing Autophagy Through the TyrRS-PARP1-SIRT1 Signaling Pathway.

560 | May 19 2018

Deng H et al. found that RSV attenuated neurotoxicity caused by Aβ25-35 through inducing autophagy in PC12 cells, and the autophagy was partially mediated via activation of the TyrRS-PARP1-SIRT1 signaling pathway. [Read the Full Post]

Dihydroartemisinin restricts hepatic stellate cell contraction via an FXR-S1PR2-dependent mechanism

562 | May 09 2018

Xu W et al. suggested that DHA could restrict HSC contraction through modulating FXR/S1PR2 pathway-mediated Ca(2+) -dependent and Ca(2+) -sensitization signaling. Our discoveries make DHA a potential candidate for portal hypertension. [Read the Full Post]

PPARβ/δ activation protects against corticosterone-induced ER stress in astrocytes by inhibiting the CpG hypermethylation of microRNA-181a

1356 | May 06 2018

Ji J et al. suggested that PPARβ/δ activation in astrocytes might be a promising target for regulating ER stress-induced astrocytic injury. [Read the Full Post]

Lipopolysaccharide and heat stress impair the estradiol biosynthesis in granulosa cells via increase of HSP70 and inhibition of smad3 phosphorylation and nuclear translocation

1049 | May 01 2018

Li H et al. suggested that LPS and heat stress could impair estradiol biosynthesis in GCs via increased HSP70 and indirect inhibition of Smad3 phosphorylation and nuclear translocation. [Read the Full Post]

Abrogating cholesterol esterification suppresses growth and metastasis of pancreatic cancer

641 | Apr 30 2018

Li J et al. demonstrated a new strategy for treating metastatic pancreatic cancer by inhibiting cholesterol esterification. [Read the Full Post]

PPARβ/δ activation protects against corticosterone-induced ER stress in astrocytes by inhibiting the CpG hypermethylation of microRNA-181a

544 | Apr 27 2018

Ji J et al. suggested that PPARβ/δ activation in astrocytes might be a promising target for regulating ER stress-induced astrocytic injury. [Read the Full Post]

Activation of carbonic anhydrase IX by alternatively spliced tissue factor under late-stage tumor conditions.

576 | Apr 21 2018

Ramchandani D et al. found that CAIX is a novel downstream mediator of asTF in pancreatic cancer, particularly under hypoxic conditions that model late-stage tumor microenvironment. [Read the Full Post]

Tanshinone I inhibits tumor angiogenesis by reducing Stat3 phosphorylation at Tyr705 and hypoxia-induced HIF-1α accumulation in both endothelial and tumor cells

559 | Apr 12 2018

Wang Y et al. revealed unique characteristics of tanshinone-1 and its improved derivatives as promising angiogenesis inhibitors. [Read the Full Post]

Neuroprotective effects of piperine on the 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine-induced Parkinson's disease mouse model.

0 | Apr 06 2018

Yang W et al. showed that piperine exerts a protective effect on dopaminergic neurons via antioxidant, anti-apoptotic, and anti-inflammatory mechanisms in an MPTP-induced mouse model of PD [Read the Full Post]

Tsc1 expression by dendritic cells is required to preserve T-cell homeostasis and response

0 | Mar 28 2018

Luo Y et al. identified Tsc1 as a crucial signaling checkpoint in DCs essential for preserving T-cell homeostasis and response. [Read the Full Post]

Significance of alpha smooth muscle actin expression in traumatic painful neuromas: a pilot study in rats

602 | Mar 28 2018

Weng W et al. provided new insights into the development of new treatment modalities for the management of intractable painful neuromas. [Read the Full Post]

Characterization of osimertinib (AZD9291)-resistant non-small cell lung cancer NCI-H1975/OSIR cell line

985 | Mar 03 2018

Tang ZH et al. showed that EGFR could pose as one of the OSI-resistant mechanisms and navitoclax might be the candidate drug for OSI-resistant NSCLC patients. [Read the Full Post]

Loss-of-function screens of druggable targetome against cancer stem-like cells

899 | Feb 19 2018

Song M, et al. provided a useful resource that can be exploited for the selective elimination of CSLCs. [Read the Full Post]

Dihydroartemisinin protects against alcoholic liver injury through alleviating hepatocyte steatosis in a farnesoid X receptor-dependent manner

664 | Feb 15 2018

Xu W et al. indicated DHA significantly improved alcoholic liver injury by inhibiting hepatic steatosis, which was dependent on its activation of FXR in hepatocytes. [Read the Full Post]

Histochemical examination of the effects of high-dose 1,25(OH)2D3 on bone remodeling in young growing rats

605 | Feb 13 2018

Sun J et al. suggested that long-term use of physiologically-high dose calcitriol may result in bone loss through RANKL/RANK/osteoprotegerin and EphrinB2-EphB4 signaling pathways, and that these negative effects could continue after drug withdrawal. Therefore, optimal limits for vitamin D administration need to be established for children and adolescents. [Read the Full Post]

Fasting-induced hormonal regulation of lysosomal function.

0 | Feb 12 2018

Chen L et al. indicated the FGF21-TFEB signaling axis links lysosome homeostasis with extracellular hormonal signaling to orchestrate lipid metabolism during fasting. [Read the Full Post]

FOXM1 evokes 5-fluorouracil resistance in colorectal cancer depending on ABCC10

609 | Feb 07 2018

Xie T et al. suggested that FOXM1/ABCC10 axis may serve as a potential therapeutic target for 5-FU resistance in CRC patients. [Read the Full Post]

Efficacy of continuous EGFR-inhibition and role of Hedgehog in EGFR acquired resistance in human lung cancer cells with activating mutation of EGFR

0 | Jan 20 2018

Della Corte CM et al. found that EGFR-mutant NSCLC can benefit from continuous treatment with EGFR-inhibitors, indepenently from mechanisms of resistance [Read the Full Post]

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

1929 | 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]

Simvastatin augments revascularization and reperfusion in a murine model of hind limb ischemia - Multimodal imaging assessment

672 | Jan 09 2018

Goggi JL et al. identified using 99mTc-RGD SPECT, which displays significant increases in retention before macrovascular volume changes are measureable with MRI. [Read the Full Post]

BCL6 modulation of acute lymphoblastic leukemia response to chemotherapy

632 | Dec 27 2017

Slone WL et al. suggested that BCL6 is one factor, modulated by microenvironment derived cues that may contribute to regulation of ALL therapeutic response. [Read the Full Post]

CK2α' Drives Lung Cancer Metastasis by Targeting BRMS1 Nuclear Export and Degradation

0 | Dec 02 2017

Liu Y et al. identified a therapeutically exploitable posttranslational mechanism by which CK2α-mediated degradation of BRMS1 promotes metastases in lung cancer. [Read the Full Post]

HSP90 activity is required for MLKL oligomerisation and membrane translocation and the induction of necroptotic cell death

1356 | Nov 29 2017

Jacobsen AV et al. implicated HSP90 as a modulator of necroptosis at the level of MLKL, a function that complements HSP90's previously demonstrated modulation of the upstream necroptosis effector kinases, RIPK1 and RIPK3. [Read the Full Post]

The HSP90 inhibitor XL888 overcomes BRAF inhibitor resistance mediated through diverse mechanisms

1576 | Nov 25 2017

Paraiso KH et al.showed that HSP90 inhibition may be a highly effective strategy at managing the diverse array of resistance mechanisms being reported to BRAF inhibitors and appears to be more effective at restoring BIM expression and downregulating Mcl-1 expression than combined MEK/PI3K inhibitor therapy. [Read the Full Post]

Hsp90β promoted endothelial cell-dependent tumor angiogenesis in hepatocellular carcinoma

1372 | Nov 24 2017

Meng J et al. investigated the correlation between Hsp90β expression and CD31+ endothelial cell-dependent vessel density. [Read the Full Post]

HSP90 Shapes the Consequences of Human Genetic Variation

0 | Nov 14 2017

Karras GI et al. provided one plausible mechanism for the variable expressivity and environmental sensitivity of genetic diseases. [Read the Full Post]

Canonical hedgehog signalling regulates hepatic stellate cell-mediated angiogenesis in liver fibrosis

1695 | Oct 16 2017

Zhang F et al. provided evidence that the canonical hedgehog pathway controlled HSC-mediated liver angiogenesis. Selective inhibition of HSC hedgehog signalling could be a promising therapeutic approach for hepatic fibrosis. [Read the Full Post]

Regulation of the Nampt-mediated NAD salvage pathway and its therapeutic implications in pancreatic cancer

793 | Oct 10 2017

Ju HQ et al. suggested that Nampt inhibition may override gemcitabine resistance by decreasing the NAD level and suppressing glycolytic activity, warranting further clinical investigation for pancreatic cancer treatment. [Read the Full Post]

HSP90 Shapes the Consequences of Human Genetic Variation

0 | Sep 26 2017

Karras GI et al. provided one plausible mechanism for the variable expressivity and environmental sensitivity of genetic diseases. [Read the Full Post]

HSP90 Shapes the Consequences of Human Genetic Variation

1491 | Sep 25 2017

Karras GI et al. provided one plausible mechanism for the variable expressivity and environmental sensitivity of genetic diseases. [Read the Full Post]

Inhibition of glioblastoma cell proliferation, migration and invasion by the proteasome antagonist carfilzomib

1181 | Sep 22 2017

Areeb Z et al. showed that carfilzomib represents a novel, yet FDA-approved agent for the treatment of glioblastoma multiforme. [Read the Full Post]

A Schisandra-Derived Compound Schizandronic Acid Inhibits Entry of Pan-HCV Genotypes into Human Hepatocytes

913 | Sep 21 2017

Qian XJ et al. suggested that SZA potently inhibited pan-HCV genotype entry into hepatoma cells and primary human hepatocytes without interfering virus binding on cell surface or internalization. However, virion-cell fusion process was impaired in the presence of SZA, along with the increased host membrane fluidity. We also found that SZA inhibited the spread of HCV to the neighboring cells, and combinations of SZA with interferon or telaprevir resulted in additive synergistic effect against HCV. Additionally, SZA diminished the establishment of HCV infection in vivo. The SZA target is different from conventional direct-acting antiviral agents, therefore, SZA is a potential therapeutic compound for the development of effective HCV entry inhibitors, especially for patients who need to prevent HCV reinfection during the course of liver transplantations. [Read the Full Post]

Hyperthermia reduces migration of osteosarcoma by suppression of autocrine motility factor

1610 | Sep 09 2017

Nakajima K et al. indicated hyperthermia reduced AMF expression and tumor cell motility via HSP27 and may therefore be applied as osteosarcoma treatment. [Read the Full Post]

Potentiating the antitumour response of CD8(+) T cells by modulating cholesterol metabolism

1133 | Jun 21 2017

Yang W, et al. used the ACAT inhibitor avasimibe, which was previously tested in clinical trials for treating atherosclerosis and showed a good human safety profile, to treat melanoma in mice and observed a good antitumour effect. [Read the Full Post]

A repurposing strategy for Hsp90 inhibitors demonstrates their potency against filarial nematodes

0 | Jun 05 2017

Gillan V et al. provided proof of principle that the repurposing of currently available Hsp90 inhibitors may have potential for the development of novel agents with macrofilaricidal properties. [Read the Full Post]

Phosphodiesterase 5/protein kinase G signal governs stemness of prostate cancer stem cells through Hippo pathway

921 | Jun 01 2017

Liu N et al. suggested that PDE5 inhibitors in combination with chemotherapeutic agents could effectively prevent initiation, metastasis, and relapse of prostate cancer. [Read the Full Post]

The effect of hyperlipidemia on the pharmacokinetics, hepatic and pulmonary uptake of posaconazole in rat

0 | May 20 2017

Khalil HA et al. induced lipoprotein level elevation caused alterations in the PSZ pharmacokinetics and decreased its hepatic and pulmonary uptake. [Read the Full Post]

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

3533 | 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]

Specificity of anti-prostate cancer CYP17A1 inhibitors on androgen biosynthesis

967 | Apr 08 2017

Udhane SS et al. concluded that orteronel is a highly specific inhibitor of 17,20 lyase activity. [Read the Full Post]

A chemical with proven clinical safety rescues Down-syndrome-related phenotypes in through DYRK1A inhibition

1958 | Apr 06 2017

Kim H et al. demonstrated that CX-4945 is a potent DYRK1A inhibitor and also suggested that it has therapeutic potential for DYRK1A-associated diseases. [Read the Full Post]

A Repurposing Strategy for Hsp90 Inhibitors Demonstrates Their Potency against Filarial Nematodes

1 | Mar 27 2017

Gillan V et al provided proof of principle that the repurposing of currently available Hsp90 inhibitors may have potential for the development of novel agents with macrofilaricidal properties. [Read the Full Post]

The-cyclic-GMP-protein-kinase-G-pathway-as-a-therapeutic-target-in-head-and-neck-squamous-cell-carcinoma

973 | Mar 19 2017

Tuttle TR et al found that Tadalafil substantially reduced the growth of CAL27-derived tumors in athymic mice. Several drugs which either activate sGC or inhibit PDE5 are approved for treatment of nonmalignant conditions. These drugs could be repurposed as novel and effective therapeutics in patients with head and neck cancer. [Read the Full Post]

Pioglitazone Suppresses CXCR7 Expression To Inhibit Human Macrophage Chemotaxis through Peroxisome Proliferator-Activated Receptor γ

2122 | Mar 16 2017

Zhao D et al found that pioglitazone suppresses CXCR7 expression to inhibit human macrophage chemotaxis through PPARγ. [Read the Full Post]

Heat shock protein 90 inhibitors induce functional inhibition of human natural killer cells in a dose-dependent manner

1686 | Mar 14 2017

Huyan T et al. suggested that more attention should be given to the effect of Hsp90 inhibitors on NK cell function during clinical trials and also represent a potential immunosuppressant strategy. [Read the Full Post]

SIRT1 prevents hyperuricemia via the PGC-1α/PPARγ-ABCG2 pathway

1060 | Mar 09 2017

Wang J et al. found that one possible mechanism is the activation of ABCG2 in the ileum through the PGC-1α/PPARγ pathway. [Read the Full Post]

In vitro antifungal synergy between amphiphilic aminoglycoside K20 and azoles against Candida species and Cryptococcus neoformans

0 | Mar 07 2017

Shrestha SK et al. suggested that combinations of K20 and azoles offer a possible strategy for developing therapies against candidiasis. [Read the Full Post]

Nitric oxide plays a dual role in the oxidative injury of cultured rat microglia but not astroglia

0 | Feb 04 2017

Wang JY et al. suggested that NO exhibits a concentration-dependent dual action of weakening or enhancing oxidative injury in mixed glia, particularly microglia. [Read the Full Post]

A repurposing strategy for Hsp90 inhibitors demonstrates their potency against filarial nematodes

3935 | Jan 29 2017

Gillan V et al. provided proof of principle that the repurposing of currently available Hsp90 inhibitors may have potential for the development of novel agents with macrofilaricidal properties. [Read the Full Post]

Nitric oxide plays a dual role in the oxidative injury of cultured rat microglia but not astroglia

0 | Jan 26 2017

Wang JY et al. suggested that NO exhibits a concentration-dependent dual action of weakening or enhancing oxidative injury in mixed glia, particularly microglia. [Read the Full Post]

Pioglitazone Suppresses CXCR7 Expression To Inhibit Human Macrophage Chemotaxis through Peroxisome Proliferator-Activated Receptor γ

1278 | Jan 23 2017

Zhao D, et al.'s data demonstrate that pioglitazone suppresses CXCR7 expression to inhibit human macrophage chemotaxis through PPARγ. [Read the Full Post]

Heat shock protein 90 inhibitors induce functional inhibition of human natural killer cells in a dose-dependent manner

1819 | Jan 22 2017

Huyan T, et al.'s findings suggest that more attention should be given to the effect of Hsp90 inhibitors on NK cell function during clinical trials and also represent a potential immunosuppressant strategy. [Read the Full Post]

In vitro antifungal synergy between amphiphilic aminoglycoside K20 and azoles against Candida species and Cryptococcus neoformans

1269 | Jan 18 2017

Shrestha SK et al. suggested that combinations of K20 and azoles offer a possible strategy for developing therapies against candidiasis. [Read the Full Post]

Nitric oxide plays a dual role in the oxidative injury of cultured rat microglia but not astroglia

2130 | Jan 01 2017

Wang JY et al. suggested that NO exhibits a concentration-dependent dual action of weakening or enhancing oxidative injury in mixed glia, particularly microglia. [Read the Full Post]

The cyclic GMP/protein kinase G pathway as a therapeutic target in head and neck squamous cell carcinoma

0 | Sep 04 2016

Tuttle TR, et al. found that several drugs which either activate sGC or inhibit PDE5 are approved for treatment of nonmalignant conditions. These drugs could be repurposed as novel and effective therapeutics in patients with head and neck cancer. [Read the Full Post]

An unusual mechanism of ERBB4 in regulating tumor related gene expression

8818 | 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]

ERK/Cdk5 axis regulates diabetes-related PPARγ phosphorylation

7310 | Nov 21 2014

Recently, Banks et al. discovered that ERK/Cdk5 axis is involved in regulation PPARγ activities, and the inhibition of ERK and MEK leads to the improvement of insulin resistance. [Read the Full Post]

Gsk256066 is a potent and selective inhaled PDE4 inhibitor

2479 | Jan 24 2014

GSK256066 is a selective PDE4B(equal affinity to isoforms A-D) inhibitor with IC50 of 3.2 pM, >380,000-fold selectivity versus PDE1/2/3/5/6 and >2500-fold selectivity against PDE4B versus PDE7. [Read the Full Post]

Learn about the prescription medication Methazolamide

2546 | May 26 2013

Methazolamide is a carbonic anhydrase inhibitor with Ki of 50 nM, 14 nM and 36 nM for hCA I, hCA II and bCA IV isoforms, respectively. [Read the Full Post]

Effects of oral administration of methazolamide on intraocular pressure

2478 | May 22 2013

In vitro characterization of the erythrocyte distribution of methazolamide: a model of erythrocyte transport and binding kinetics [Read the Full Post]

MDV3100 was found clinically active for metastatic

2678 | Apr 18 2013

MDV3100 is an androgen receptor antagonist drug developed by the pharmaceutical company Medivation for the treatment of metastatic castration-resistant prostate cancer. [Read the Full Post]

Enzalutamide is an androgen receptor inhibitor

2210 | Feb 27 2013

Little is known of pathways involved in upstream control of Notch1 gene expression and activity in keratinocytes, and mammalian cells in general. To address this issue we undertook a chemical genetics approach. Rather than screening a large collection of unknown chemicals, enzalutamide we chose a library of 489 compounds [Read the Full Post]

ONCOGENES AND HSP90 INHIBITORS

4695 | Aug 24 2012

PATHWAY OF HSP90 AND CANCER CELL LINES: Heat shock protein 90 or Hsp90 is actually a non-fibrous protein which gained its name from its molecular weight that is 90kDa. Hsp90 is most abundant cytoplasmic protein which plays a significant role in cells by acting like a molecular chaperone for many proteins related to some important signaling cascades of the cell. Different proteins chaperones that are existing in the cell, involve serine/theronine kinases and tyrosine kinases as well hence they are very much important for the proper regulation of cell growth and cell cycle. A detailed research is carried out to describe the relation between Hsp90 and cancers. To inhibit this chaperone i.e. Hsp90, the simple strategy of designing Hsp protein inhibitor was developed when Hsp90 was found to be existing in different cancerous cell lines activated through the activation of oncogenes. It has been proved a very fruitful therapy for cancer. [Read the Full Post]

HSP90 INHIBITORS AND ONCOGENES

4953 | Aug 16 2012

HSP90 CASCADE AND CANCER CELLS: Hsp90 or the Heat shock protein 90 is a non fibrous protein that gained its name on the basis of its molecular weight i.e., 90kDa. Heat shock protein 90 is the most abundant protein present in cytoplasm that plays a significant role in the cells by acting as molecular chaperones for different proteins associated with some important signaling pathways in the cells. Various molecular chaperones existing in the cells, involves in the tyrosine kinases and serine/theronine kinases as well, so they are very important for proper regulation of cell cycle and cell growth. A complete research has been done to describe the relation between cancer and Hsp90. For the inhibition of Hsp90 chaperone a simple strategy is designed i.e., development of Hsp-60 inhibitor in case of presence of Hsp90 in the cancerous cells and activated by the activation of various oncogenes. It was proved to be an efficient therapy for the treatment of cancer. [Read the Full Post]

HSP90 INHIBITORS AND ONCOGENES

4723 | Aug 02 2012

HSP90 PATHWAY AND CANCER CELLS: Heat shock protein 90 or Hsp90 is a non-fibrous protein that has gained its name from its 90kDa molecular weight. This is the most abundant protein present in cytoplasm and plays an important role in the cell by acting as a chaperone for many of the proteins involved in important signaling pathways of the cell. There are various proteins chaperones which are present in the cell, includes TKs or tyrosine kinases and theronine/serine kinases as well and these are very important for the regulation of cell cycle and growth. Detailed research has been conducted to connect cancers and Hsp90. As Hsp90 has shown by different cancerous cells which are activated via activating oncogenes a simple strategy for the inhibition of this chaperone has developed by designing Hsp90 inhibitors. This approach has been fruitful for cancer therapy. [Read the Full Post]

HSP INHIBITORS AGAINST PROTEIN FOLDING

4011 | Mar 19 2012

Introduction: Cellular Quality Assurance The network of chemical reactions linked to the mechanisms behind cellular growth, proliferation and differentiation are complex. Referred to as biochemical pathways these mechanisms operate on some simple principles starting with the receipt of a message from the host system to the cell itself. The pathway system can be likened to a production line facility with the product being a normal health cell. So mechanisms exists for stock piling of raw materials, for the synthesis of component parts, for the recycling of waste materials, for the removal of unwelcome molecules, quality assurance and final product viability. One the key aspects of cellular growth is the delicacy of the whole process, it does not take much to drive a mechanism off balance and produce a faulty product, to ensure quality under stress induced conditions a series of proteins exist referred to as Heat Shock Proteins that assess the quality of proteins being constructed for cell growth purposes. [Read the Full Post]

TOSEDOSTAT: INHIBITING AMINOPEPTIDASES IN CANCERS

2945 | Mar 18 2012

AMINOPEPTIDASES AND THEIR INHIBITION: Aminopeptidases catalyze the cleavage of amino acids of proteins or peptide substrates. Such enzymes are zinc dependant and located throughout most mammalian tissue and in certain plant extracts. They are essential for many cellular maintenance functions and are release systemically from the small intestine. Since these enzymes act by hydrolysis amino acids located at the amino groups of terminal proteins inhibition of their processes would affect cell proliferation, secretion, invasion and angiogenesis. Small molecule inhibitors for the inhibition of aminopeptidases have been developed for oncological use. CHR-2797 is a pro-drug for an aminopeptidase inhibitor that is marketed by Chroma Therapeutics under the trade name of Tosedostat. Tosedostat aminopeptidase inhibitor under goes cellular modulation to the active metabolite (CHR79888) via hydrolysis of a methoxy group. This metabolite is poorly membrane permeable, resulting in cellular accumulation. In animal models Toseostad has proved to be a significant inhibitor of proliferation and has demonstrated anti-angiogenic activity. [Read the Full Post]

Roles of Hsp90 in wound healing and cancer

5244 | Oct 24 2011

Wound healing is an intricate process in which the skin (or another organ-tissue) repairs itself after injury. At present, local growth factors are considered to be the driving force for wound healing and only recombinant human platelet-derived growth factor-BB (PDGF-BB) has been approved by US FDA for topical treatment of diabetic ulcers. However, the use of PDGF-BB in clinical trials has been limited for its modest efficacy, high cost and risk of causing cancer. Thus, novel treatment for wound healing is needed to be explored. [Read the Full Post]

Chiosis, G., M. Vilenchik, et al. (2004). "Hsp90: the vulnerable chaperone." Drug Discov Today 9(20): 881-888.

3930 | Apr 19 2011

Agents that interact with its C-terminus or modify its post-translational status represent additional ways of interfering with chaperone activity. This review will discuss several emerging classes of Hsp90 inhibitors and their modes of action. [Read the Full Post]