BI-3406 is a potent (IC50 = 5 nM), selective, and orally bioavailable SOS1 inhibitor.1 It blocks SOS1 interaction with KRAS preventing activation of KRAS. BI-3406 was active against multiple cancer cell types and xenograft models harboring various KRAS mutant alleles including G12C,V,S,A,and G13D. It displayed strong synergistic effects with the MEK inhibitor trametinib1,2 and this combination was able to overcome resistance to the KRAS inhibitors sotorasib and adagrasib3. BI-3406 acted synergistically with the KRAS inhibitor adagrasib in KRAS G12C mutant lung and colorectal cancer models.4
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