KRAS R68G继发突变引发KRASG12D靶向抑制剂MRTX1133耐药的机制研究

王高明, 崔然, 黎彦璟, 刘颖斌

Study on the mechanism of KRAS R68G secondary mutation-induced resistance to KRASG12D-targeted inhibitor MRTX1133

WANG Gaoming, CUI Ran, LI Yanjing, LIU Yingbin

图1 MRTX1133和KRAS中MRTX1133的结合口袋及相关的耐药突变 Note： A. Chemical structure of MRTX1133. B. The MRTX1133 binding pocket (PDB ID: 7RPZ). C. Six secondary mutations, including V9E, V9W, V9Q, T58Y, Y96W and Q99L, cause significant steric hindrance or block the formation of interactions between MRTX1133 and KRAS. Red areas stand for steric clashes.

Fig 1 MRTX1133 and its binding pocket in KRAS, and associated resistance mutations