SY-14556

SY-14556 is a highly potent and selective small molecule reactivator of the p53 Y220C mutant, a hotspot mutation found in approximately 1% of solid tumors. Developed by Shouyao Holding (Beijing) Co., Ltd., the compound is designed to pharmacologically stabilize the destabilized Y220C mutant protein into a wild-type-like conformation. This restoration of function allows p53 to regain its DNA-binding capacity and transcriptionally activate downstream target genes such as p21 and MDM2, which mediate cell cycle arrest and apoptosis. In preclinical models, SY-14556 demonstrated an EC50 of less than 5 nM for DNA binding and showed over 100-fold selectivity for mutant cells over wild-type p53 cells, resulting in robust anti-tumor activity in xenograft models.