Delving into the Latest Updates on Kinetek Pharmaceuticals, Inc. with Synapse

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项与 Kinetek Pharmaceuticals, Inc. 相关的药物

Oremepermin alfa

靶点

Protein kinases

作用机制

蛋白激酶抑制剂

在研机构

Kringle Pharma, Inc. [+1]

原研机构

Kringle Pharma, Inc.

在研适应症

声带功能障碍 [+3]

非在研适应症

龋齿 [+2]

最高研发阶段临床3期

首次获批国家/地区-

首次获批日期-

KP-211

靶点-

作用机制-

在研机构-

原研机构

Kinetek Pharmaceuticals, Inc.

在研适应症-

非在研适应症

肿瘤

最高研发阶段终止

首次获批国家/地区-

首次获批日期-

100 项与 Kinetek Pharmaceuticals, Inc. 相关的临床结果

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0 项与 Kinetek Pharmaceuticals, Inc. 相关的专利（医药）

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6

项与 Kinetek Pharmaceuticals, Inc. 相关的文献（医药）

2005-02-15·Cancer Research

Inhibition of Integrin-Linked Kinase by a Selective Small Molecule Inhibitor, QLT0254, Inhibits the PI3K/PKB/mTOR, Stat3, and FKHR Pathways and Tumor Growth, and Enhances Gemcitabine-Induced Apoptosis in Human Orthotopic Primary Pancreatic Cancer Xenografts

Article

作者: Sutton, Kymberley L. ; Wheeler, Jeffery J. ; Hedley, David W. ; Yau, Cindy Y.F.

AbstractIntegrin-linked kinase (ILK) couples integrins and growth factors to downstream signaling pathways involving phosphatidylinositol 3-kinase, protein kinase B/Akt (PKB/Akt), and glycogen synthase kinase-3β. The anticancer effects of ILK inhibitor QLT0254 were tested in an orthotopic primary xenograft model of pancreatic cancer. The pharmacodynamic effects of a single dose of QLT0254 on the phosphorylation of PKB/Akt were measured by immunohistochemistry and Western blotting, and showed a decrease of >80% after 2 hours, followed by recovery over 24 hours, consistent with the pharmacokinetic profile of this compound in mice. There was also suppression in phosphorylated PKB Thr308, forkhead in rhabdomyosarcoma, S6K1, S6, 4E-BP1, and signal transducers and activators of transcription 3 Tyr705 and Ser727 protein levels with ILK inhibition by QLT0254. However, we did not observe an effect on phosphoinositide-dependent kinase 1, glycogen synthase kinase-3β, and extracellular signal-regulated kinase phosphorylation or on total PKB and ILK protein expression levels with QLT0254 treatment. In tumor growth inhibition experiments, daily treatment with QLT0254 for 3 weeks was well tolerated and produced significant tumor growth inhibition compared with vehicle control (P = 0.001). When a single dose of QLT0254 and chemotherapy agent gemcitabine was administered, there was a significant 5.4-fold increase in acute apoptosis in the combination therapy group compared with vehicle controls (P = 0.002). However, the acute effects of QLT0254 on proliferation were not statistically significant. These results show in vivo evidence that ILK plays a prominent role in oncogenic phosphatidylinositol 3-kinase/PKB signaling in vivo with major impact on the mammalian target of rapamycin, signal transducers and activators of transcription 3, and forkhead in rhadomyosarcoma signaling pathways, suggesting that ILK inhibitors might show activity in pancreatic cancer patients.

2004-10-01·Molecular Cancer Therapeutics2区 · 医学

Inhibition of Chk1 by the G2 DNA damage checkpoint inhibitor isogranulatimide

2区 · 医学

Article

作者: Zhao, Baoguang ; Leong, Dan ; Britton, Robert ; Piers, Edward ; Roberge, Michel ; Andersen, Raymond J. ; Sanghera, Jasbinder S. ; Jiang, Xiuxian ; Lim, Lynette Y. ; Zhou, Bin-Bing S.

AbstractInhibitors of the G2 DNA damage checkpoint can selectively sensitize cancer cells with mutated p53 to killing by DNA-damaging agents. Isogranulatimide is a G2 checkpoint inhibitor containing a unique indole/maleimide/imidazole skeleton identified in a phenotypic cell-based screen; however, the mechanism of action of isogranulatimide is unknown. Using natural and synthetic isogranulatimide analogues, we show that the imide nitrogen and a basic nitrogen at position 14 or 15 in the imidazole ring are important for checkpoint inhibition. Isogranulatimide shows structural resemblance to the aglycon of UCN-01, a potent bisindolemaleimide inhibitor of protein kinase Cβ (IC50, 0.001 μmol/L) and of the checkpoint kinase Chk1 (IC50, 0.007 μmol/L). In vitro kinase assays show that isogranulatimide inhibits Chk1 (IC50, 0.1 μmol/L) but not protein kinase Cβ. Of 13 additional protein kinases tested, isogranulatimide significantly inhibits only glycogen synthase kinase-3β (IC50, 0.5 μmol/L). We determined the crystal structure of the Chk1 catalytic domain complexed with isogranulatimide. Like UCN-01, isogranulatimide binds in the ATP-binding pocket of Chk1 and hydrogen bonds with the backbone carbonyl oxygen of Glu85 and the amide nitrogen of Cys87. Unlike UCN-01, the basic N15 of isogranulatimide interacts with Glu17, causing a conformation change in the kinase glycine-rich loop that may contribute importantly to inhibition. The mechanism by which isogranulatimide inhibits Chk1 and its favorable kinase selectivity profile make it a promising candidate for modulating checkpoint responses in tumors for therapeutic benefit.

2001-06-01·Annual Review of Biophysics and Biomolecular Structure

Biomolecular Simulations: Recent Developments in Force Fields, Simulations of Enzyme Catalysis, Protein-Ligand, Protein-Protein, and Protein-Nucleic Acid Noncovalent Interactions

Review

作者: Kollman, Peter A. ; Donini, Oreola ; Reyes, Carolina M. ; Wang, Wei

▪ Abstract Computer modeling has been developed and widely applied in studying molecules of biological interest. The force field is the cornerstone of computer simulations, and many force fields have been developed and successfully applied in these simulations. Two interesting areas are (a) studying enzyme catalytic mechanisms using a combination of quantum mechanics and molecular mechanics, and (b) studying macromolecular dynamics and interactions using molecular dynamics (MD) and free energy (FE) calculation methods. Enzyme catalysis involves forming and breaking of covalent bonds and requires the use of quantum mechanics. Noncovalent interactions appear ubiquitously in biology, but here we confine ourselves to review only noncovalent interactions between protein and protein, protein and ligand, and protein and nucleic acids.

100 项与 Kinetek Pharmaceuticals, Inc. 相关的药物交易

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100 项与 Kinetek Pharmaceuticals, Inc. 相关的转化医学

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