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- W2009308766 abstract "The TGFβ type I receptor kinase (ALK5) is an attractive target for intervention in TGFβ signaling due to its druggability as well as its centrality and specificity in the pathway. A number of potent, selective ALK5 inhibitors have been discovered which interact with the ATP-binding site of ALK5. Crystallographic studies of these molecules bound to ALK5 have provided an understanding of potency and selectivity achieved by these inhibitors. ALK5 kinase inhibitors are potently active in models of cancer due to mechanisms of action similar to those for other TGFβ inhibitory agents. Recent insights into the function of TGFβ in human tumors as well as in preclinical models of cancer are helping to identify potential target patient populations and drug combinations for the development of ALK5 kinase inhibitors and other TGFβ- targeted therapeutics. Differences in the toxicological effects, pharmacokinetics and clinical side effects of ALK5 kinase inhibitors and other TGFβ-targeted agents provide a useful and differentiated set of TGFβ signaling inhibitory agents to investigate in clinical studies. Keywords: Transforming growth factor-β, Cancer, Transforming growth factor-β type I receptor kinase inhibitor, Activin receptor-like kinase 5 inhibitor, ALK5 inhibitor, Transforming growth factor-β receptor kinase inhibitor, human tumors, Smad-mediated gene expression, clinical trials, targeted therapies, ALK5 small molecule binding pockets, Smad signaling, kinase inhibitors, hydrophobic back pocket, hydrogen bond" @default.
- W2009308766 created "2016-06-24" @default.
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- W2009308766 date "2011-12-01" @default.
- W2009308766 modified "2023-10-10" @default.
- W2009308766 title "TGF-Beta Type I Receptor (Alk5) Kinase Inhibitors in Oncology" @default.
- W2009308766 doi "https://doi.org/10.2174/138920111798808257" @default.
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