CY303

CY303 is an orally available small molecule molecular glue degrader designed to target the translation termination factor G1 to S phase transition 1 (GSPT1). Developed by Cyrus Therapeutics, CY303 works by mediating the recruitment of GSPT1 to the Cereblon (CRBN) E3 ubiquitin ligase complex, leading to the polyubiquitination and subsequent proteasomal degradation of GSPT1. The depletion of GSPT1 disrupts protein synthesis and triggers the integrated stress response, ultimately leading to apoptosis in cancer cells. CY303 is currently in Phase 1 clinical development for the treatment of advanced solid tumors, with preclinical evidence also supporting its potential efficacy in hematological malignancies such as acute myeloid leukemia (AML).