SY-9453

SY-9453 is an orally bioavailable small molecule inhibitor of Protein Arginine Methyltransferase 5 (PRMT5) developed by Shouyao Holdings (Beijing) Co., Ltd. It is specifically designed to treat advanced or metastatic solid tumors that harbor a homozygous deletion of the methylthioadenosine phosphorylase (MTAP) gene. This genetic alteration, found in approximately 15% of human cancers, leads to the accumulation of the metabolite methylthioadenosine (MTA). SY-9453 leverages a synthetic lethal approach by selectively targeting PRMT5 in the presence of high MTA levels, which is intended to provide a wider therapeutic window and reduced hematological toxicity compared to first-generation, non-selective PRMT5 inhibitors. The drug is currently undergoing Phase I clinical evaluation for safety, tolerability, and preliminary efficacy in patients with MTAP-deficient solid tumors.