128269-82-9Relevant articles and documents
Discovery of a Pyrimidothiazolodiazepinone as a Potent and Selective Focal Adhesion Kinase (FAK) Inhibitor
Groendyke, Brian J.,Nabet, Behnam,Mohardt, Mikaela L.,Zhang, Haisheng,Peng, Ke,Koide, Eriko,Coffey, Calvin R.,Che, Jianwei,Scott, David A.,Bass, Adam J.,Gray, Nathanael S.
, p. 30 - 38 (2021/01/11)
Focal adhesion kinase (FAK) is a tyrosine kinase with prominent roles in protein scaffolding, migration, angiogenesis, and anchorage-independent cell survival and is an attractive target for the development of cancer therapeutics. However, current FAK inhibitors display dual kinase inhibition and/or significant activity on several kinases. Although multitargeted activity is at times therapeutically advantageous, such behavior can also lead to toxicity and confound chemical-biology studies. We report a novel series of small molecules based on a tricyclic pyrimidothiazolodiazepinone core that displays both high potency and selectivity for FAK. Structure-activity relationship (SAR) studies explored modifications to the thiazole, diazepinone, and aniline "tail,"which identified lead compound BJG-03-025. BJG-03-025 displays potent biochemical FAK inhibition (IC50 = 20 nM), excellent kinome selectivity, activity in 3D-culture breast and gastric cancer models, and favorable pharmacokinetic properties in mice. BJG-03-025 is a valuable chemical probe for evaluation of FAK-dependent biology.
Rearrangement of 4-(Aminothiocarbonyl)oxazoles to 5-Aminothiazoles. Synthetic and MINDO/3 MO Studies
Corrao, Stephanie L.,Macielag, Mark J.,Turchi, Ignatius J.
, p. 4484 - 4487 (2007/10/02)
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