CY001-80

CY001-80 is a highly potent and selective molecular glue degrader (MGD) that targets the Ikaros family zinc finger proteins 1 and 3 (IKZF1/3), also known as Ikaros and Aiolos. Developed by Hangzhou DAC Biotech and Junshi Biosciences, CY001-80 induces the proteasomal degradation of these transcription factors with sub-nanomolar potency (DC50). A significant pharmacological effect of CY001-80 is the upregulation of CD38 surface expression on multiple myeloma cells, which enhances the efficacy of anti-CD38 monoclonal antibodies. This property is utilized in the development of DAC-002, a degrader-antibody conjugate (DAC) where CY001-80 serves as the cytotoxic payload conjugated to the anti-CD38 antibody daratumumab. Preclinical studies have demonstrated that CY001-80 possesses superior neutrophil safety compared to other next-generation immunomodulatory drugs (IMiDs) such as mezigdomide and cemsidomide, while maintaining robust anti-tumor activity in multiple myeloma models.