Du, Guangyan; Rao, Suman; Gurbani, Deepak; Henning, Nathaniel J.; Jiang, Jie; Che, Jianwei; Yang, Annan; Ficarro, Scott B.; Marto, Jarrod A.; Aguirre, Andrew J.; Sorger, Peter K.; Westover, Kenneth D.; Zhang, Tinghu; Gray, Nathanael S. published the artcile< Structure-Based Design of a Potent and Selective Covalent Inhibitor for SRC Kinase That Targets a P-Loop Cysteine>, Application of C7H8ClN, the main research area is drug target design SRC kinase inhibitor antitumor.
SRC is a major regulator of many signaling pathways and contributes to cancer development. However, development of a selective SRC inhibitor has been challenging, and FDA-approved SRC inhibitors, dasatinib and bosutinib, are multi-targeted kinase inhibitors. Here, we describe our efforts to develop a selective SRC covalent inhibitor by targeting cysteine 277 on the P-loop of SRC. Using a promiscuous covalent kinase inhibitor (CKI) SM1-71 as a starting point, we developed covalent inhibitor 15a, which discriminates SRC from other covalent targets of SM1-71 including TAK1 and FGFR1. As an irreversible covalent inhibitor, compound 15a exhibited sustained inhibition of SRC signaling both in vitro and in vivo. Moreover, 15a exhibited potent antiproliferative effects in nonsmall cell lung cancer cell lines harboring SRC activation, thus providing evidence that this approach may be promising for further drug development efforts.
Journal of Medicinal Chemistry published new progress about Antiproliferative agents. 29027-20-1 belongs to class chlorides-buliding-blocks, and the molecular formula is C7H8ClN, Application of C7H8ClN.
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Chloride – Wikipedia,
Chlorides – an overview | ScienceDirect Topics