CRBN-SOS1 degrader

CRBN-SOS1 degrader refers to a class of bifunctional small molecules, specifically a program developed by Biotheryx using their PRODEGY platform, designed to induce the proteasomal degradation of SOS1 (Son of Sevenless homolog 1). By recruiting the Cereblon (CRBN) E3 ubiquitin ligase to SOS1, these degraders deplete the SOS1 protein, which serves as a critical guanine nucleotide exchange factor (GEF) for RAS proteins. This degradation leads to a reduction in active, GTP-loaded KRAS, HRAS, and MRAS, subsequently inhibiting downstream MAPK pathway signaling (measured by pERK and pS6 levels). Preclinical studies have demonstrated potent anti-proliferative activity across a wide range of KRAS mutations (including G12C, G12D, G12V, and G13D) and have shown strong synergy when combined with KRAS inhibitors, MEK inhibitors, or EGFR inhibitors.

Other names

SOS1 degraderSOS-1 degraderSOS 1 degraderBiotheryx SOS1 degrader