HM101207

**HM101207** is a novel, potent, and selective small-molecule SOS1-panKRAS inhibitor developed by Hanmi Pharm for treating KRAS-mutant cancers, including lung, colorectal, and pancreatic cancers. It suppresses the protein-protein interaction between Son of sevenless homolog 1 (SOS1), a guanine nucleotide exchange factor (GEF), and pan-KRAS (wild-type and various mutants), preventing GDP-to-GTP exchange and downstream MAPK signaling activation (e.g., p-ERK inhibition). Preclinical data show strong antitumor activity across KRAS, PTPN11, and NF1-mutant cell lines and xenograft models, superior synergy with KRAS G12C inhibitors (e.g., adagrasib, sotorasib), MEK inhibitors (e.g., binimetinib, trametinib), and other RAS-MAPK pathway inhibitors compared to competitors like MRTX0902, with high selectivity, low CYP inhibition/DDI potential, and ability to overcome resistance.[1][2][3][4]