南美超级胎牛血清999尝鲜特惠
新型双手性中心c-Met激酶抑制剂的设计合成与抗肿瘤活性评价
Design, Synthesis, and Evaluation of New Mesenchymal–Epithelial Transition Factor (c-Met) Kinase Inhibitors with Dual Chiral Centers
Han Yao, Yuanyuan Ren, Jun Yan, Jiadai Liu, Jinhui Hu, Ming Yan, Xingshu Li
Journal：MOLECULES
IF：4.93
DOI：10.3390/molecules27175359
PMID：36080127
Published：2022-08-23
research field：植物生物学遗传学生物化学
Abstract
A series of tepotinib derivatives with two chiral centers was designed, synthesized, and evaluated as anticancer agents. The optimal compound(R,S)-12astrongly exhibited antiproliferative activity against MHCC97H cell lines with an IC50value of 0.002 μM, compared to tepotinib (IC50= 0.013 μM). Mechanistic studies revealed that compound(R, S)-12asignificantly inhibited c-Met activation, as well as the downstream AKT signaling pathway, and suppressed wound closure. Moreover, compound(R, S)-12ainduced cellular apoptosis and cell cycle arrest at the G1phase in a dose-dependent fashion.Keywords:c-Met inhibitors;tepotinib;chiral compounds;kinase;cancer
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