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BI-0474

Names

[ CAS No. ]:
2750570-55-7

[ Name ]:
BI-0474

Biological Activity

[Description]:

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].

[Related Catalog]:

Research Areas >> Cancer
Signaling Pathways >> GPCR/G Protein >> Ras

[Target]

KRASG12C[1].


[In Vitro]

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.

[In Vivo]

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.

[References]

[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.

Chemical & Physical Properties

[ Molecular Formula ]:
C30H37N9O2S

[ Molecular Weight ]:
587.74


Related Compounds