CYRS1542

CYRS1542 is a potent, orally bioavailable molecular glue degrader (MGD) targeting GSPT1 (G1 to S phase transition 1), a translation termination factor. Developed by Cyrus Therapeutics, it works by recruiting the E3 ubiquitin ligase Cereblon (CRBN) to induce the ubiquitination and subsequent proteasomal degradation of GSPT1. This degradation halts translation termination, activates the Integrated Stress Response (ISR), and triggers TP53-independent apoptosis. CYRS1542 is specifically designed for the treatment of aggressive neuroendocrine solid cancers, such as Small Cell Lung Cancer (SCLC) and Neuroendocrine Prostate Cancer (NEPC), which often harbor TP53 and RB1 mutations. Preclinical data suggests it has a favorable safety profile and a higher therapeutic index compared to other clinical-stage GSPT1 degraders.