BI-0474 (BI 0474) is a potent, in vivo active KRAS G12C inhibitor with IC50 of 7.0 nM in GDP-KRAS::SOS1 protein-protein interaction assay.
BI-0474 binds reversibly to the switch II pocket.
BI-0474 showed potent antiproliferative activity (IC50=26 nM) on NCI-H358 cells carrying a G12C mutation, with no antiproliferative effect on cells carrying a KRASG12D mutation.
BI-0474 already showed a slightly higher second-order rate and lower KI, comparable kinact and IC50 in the biochemical assay, compared with AMG-510.
BI-0474 (40 mg/kg, i.p,) shows efficacy in an NCI-H358 non-small cell lung cancer xenograft model.
