BTX-6654

BTX-6654 is a cereblon-based bifunctional PROTAC degrader targeting the protein SOS1 (Son of sevenless homolog 1). It functions by inducing targeted degradation of SOS1, which plays an upstream role in KRAS activation. By degrading SOS1, BTX-6654 reduces downstream signaling markers such as phosphorylated ERK (pERK) and phosphorylated S6 (pS6), leading to antiproliferative effects in cells harboring various KRAS mutations. This mechanism positions BTX-6654 as a potential pan-KRAS therapeutic agent capable of overcoming resistance mechanisms associated with allele-specific KRAS inhibitors. The drug is primarily developed for the treatment of KRAS mutation-related tumors and has shown efficacy in preclinical models including xenografts with KRAS G12C mutations where it demonstrated dose-dependent tumor growth inhibition and synergy with other inhibitors like MEK inhibitors. It is currently at the preclinical stage of development for neoplasms[1][2][3][5][6][10].

Other names

BTX 6654BTX6654BTX-6654