下图是文章中总结的一些SⅡ口袋的KRAS-G12C分子,有一些在临床(并不全),其中两个来自国内(结构似乎有误,不过主要结构特征是有的)。最后两个结构相对新颖,一个来自de novostructure-based design,一个来自fragment screening + SBDD。 感兴趣可以移步之前做的一个小视...
MK-1084 is a highly potent and specific KRAS G12C-GDP macrocyclic inhibitor that was discovered from a structure-guided lead optimization effort. It exhibits a favorable preclinical potency, PK, PK/PD, efficacy, off-target and tolerability profile and has QD oral dosing potential with a ...
We leveraged structure-based drug design to identify a macrocyclic core structure, and hypothesis-driven optimization of biopharmaceutical properties to further improve metabolic stability and tolerability.Xiaoshen MaDavid L. SlomanRuchia DuggalKenneth D. Anderson...