效力
蛋氨酸腺苷转移酶
体内
药代动力学
药理学
生物利用度
化学
医学
蛋氨酸
体外
生物
生物化学
遗传学
氨基酸
作者
Qun Li,Zhiping Yang,Dong Sung An,Lifei Liu,Wen Jiang,Rongchen Liu,Jiangtao Su,Yang Jiang,Erguang Li,X. Zhang
标识
DOI:10.1021/acsmedchemlett.3c00488
摘要
Inhibition of methionine adenosyltransferase 2A (MAT2A) has received significant interest because of its implication as a synthetic lethal target in methylthioadenosine phosphorylase (MTAP)-deleted cancers. Here, we report the discovery of a series of 3H-pyrido[1,2-c]pyrimidin-3-one derivatives as novel MAT2A inhibitors. The selected compound 30 exhibited high potency for MAT2A inhibition and a favorable pharmacokinetic profile. Furthermore, in an HCT-116 MTAP-deleted xenograft model, compound 30 showed better in vivo potency than current clinical compound AG-270.
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