A SOS1 inhibitor demonstrating antitumor activity against KRAS-mutant cancers
RAS is the most mutated oncogene in various human cancers. Son of sevenless homolog 1 (SOS1) is a guanine nucleotide exchange factor (GEF) on RAS that promotes the exchange of bound GDP to GTP.
SOS1 protein is a promising therapeutic target in RAS-mutant and other RTK-altered cancers.
A novel SOS1 inhibitor, HM99462, potently inhibits interaction of KRAS-SOS1.
Description
Antitumor activities
Potent inhibition of p-ERK and good antitumor activity regardless of KRAS mutation types and tumor types
Very low potential of CYP enzyme inhibition, enabling to apply combination with various targeted agents
Non-inferior to superior potency on antitumor activity to competitors when combined with sotorasib
(KRAS G12C inhibitor) or trametinib (MEK inhibitor) in various KRAS-driven tumor models