TY-1091

TY-1091 is an orally bioavailable, selective, second-generation small molecule inhibitor of the proto-oncogene receptor tyrosine kinase RET (rearranged during transfection), developed by TYK Medicines. It exhibits potent and dose-dependent inhibition of RET pathway activation, including inhibition of RET phosphorylation. TY-1091 demonstrates nanomolar potency against wild-type RET as well as a broad spectrum of clinically relevant RET mutants such as G810S, V804M/L/E, compound gatekeeper and solvent front mutations (V804M/G810S), and compound driver plus solvent-front mutations (M918T/G810S). Preclinical studies have shown higher activity compared to cabozantinib and comparable efficacy to other selective RET inhibitors like pralsetinib and selpercatinib. The drug is currently in phase 1/2 clinical trials for advanced solid tumors with RET alterations, including medullary thyroid cancer (MTC) and non-small cell lung cancer (NSCLC) with RET fusions or mutations.