BTX-10908

BTX-10908 is a first-in-class, orally bioavailable small molecule degrader of SOS1 (Son of Sevenless homolog 1), a guanine nucleotide exchange factor that activates RAS proteins by converting them from the inactive GDP-bound state to the active GTP-bound state. By targeting and degrading SOS1, BTX-10908 disrupts the KRAS signaling pathway, which is frequently mutated in human cancers such as pancreatic, colorectal, and lung tumors. In preclinical models, BTX-10908 has demonstrated rapid and potent degradation of SOS1 across pan-KRAS mutant cancer cell lines and significant tumor growth inhibition in KRAS-driven models. The drug acts through a CRBN-dependent proteasomal degradation mechanism and shows greater potency than traditional SOS1 inhibitors at inhibiting downstream signaling (including pERK) and reducing cell viability. It also exhibits synergistic effects when combined with inhibitors targeting other nodes in the RTK-RAS-MAPK pathway (e.g., sotorasib, osimertinib). BTX-10908 is being developed primarily for monotherapy or combination therapy in KRAS-mutant or RTK-driven cancers[1][2][3][6].