AZD9750

AZD9750 is an investigational, orally bioavailable proteolysis targeting chimera (PROTAC) designed to degrade the androgen receptor (AR). Developed by AstraZeneca, it functions by recruiting the Cereblon (CRBN) E3 ubiquitin ligase to the AR, leading to its ubiquitination and subsequent proteasomal degradation. This mechanism allows AZD9750 to target not only wild-type AR but also amplified and mutant forms (including ligand-binding domain mutations) that often drive resistance to traditional androgen receptor signaling inhibitors like enzalutamide. It is currently being evaluated in Phase I/II clinical trials (e.g., the ANDROMEDA study) for the treatment of metastatic prostate cancer, both as a monotherapy and in combination with the PARP1-selective inhibitor saruparib (AZD5305). Preclinical data indicate that AZD9750 is significantly more potent than enzalutamide in inhibiting the proliferation of AR-dependent prostate cancer cell lines and can induce tumor regression in various patient-derived xenograft models.

Other names

AR-PROTAC