BI-0474

BI-0474 is a potent KRASG12C inhibitor with an IC50 value of 7.0 nM for the GDP-KRAS::SOS1 protein-protein interaction. BI-0474 exhibits good anti-proliferative activity against NCI-H358 cells carrying the G12C mutation. BI-0474 also shows good anti-tumour activity in non-small cell lung cancer xenograft models[1].

Research Areas >> Cancer

Signaling Pathways >> GPCR/G Protein >> Ras

KRASG12C[1].

BI-0474 (1-10,000 nM; 3 days) shows potent antiproliferative activity of 26 nM on NCI-H358 cells carrying a G12C mutation[1]. Cell Proliferation Assay[1] Cell Line: NCI-H358 cells (carrying a G12C mutation) Concentration: 1-10,000 nM Incubation Time: 3 days Result: Inhibited proliferation of NCI-H358 cells with an EC50 of 26 nM.

BI-0474 (40 mg/kg; i.p.; single daily for 3 days) shows anti-tumor efficacy and pharmacodynamic biomarker modulation in an NCI-H358 cell line-derived non-small cell lung cancer xenograft model[1]. Animal Model: NMRI nude mice (NCI-H358 cell line-derived non-small cell lung cancer xenograft model)[1]. Dosage: 40 mg/kg Administration: Intraperitoneal administration; single daily for 3 days Result: Led to induction of programmed cell death in this xenograft model.

[1]. Bröker J, et al. Fragment Optimization of Reversible Binding to the Switch II Pocket on KRAS Leads to a Potent, In Vivo Active KRASG12C Inhibitor. J Med Chem. 2022 Oct 27.