BI-3406 is an orally bioavailable, highly potent and selective KRAS/Son of Sevenless 1 (SOS1) interaction inhibitor (IC50 = 6 nM), binding to the catalytic domain of the guanine nucleotide exchange factor (GEF) SOS1 thereby preventing the interaction with KRAS-GDP. BI-3406 does not block the interaction of KRAS with SOS2 but elicits activity on a broad panel of KRAS oncogenic variants, including all major G12 and G13 oncoproteins. In KRAS-dependent cancers, BI-3406 potently reduces the formation of GTP-loaded KRAS, and inhibits MAPK pathway signaling both in vitro and in vivo. Down-modulation of this signaling cascade by BI-3406 in KRAS G12 or G13 mutant cells effectively limits cell proliferation. As a monotherapy, BI-3406 modulates signaling, as assessed by p-ERK and target genes, and displays marked anti-tumor efficacy in KRAS mutant xenografts.

KEYWORDS: BI-3406 | Suppliers | KRAS-SOS1 inhibitor | BI3406 | BI 3406 | CT-BI3406 | CAS [2230836-55-0] | GTP | KRAS | Inhibitor | Enzymes