A new investigational drug, SHR3591, is offering fresh hope for patients with metastatic castration-resistant prostate cancer (mCRPC). Developed as an oral AR PROTAC (proteolysis targeting chimera), SHR3591 is designed to degrade the androgen receptor (AR) protein, a crucial driver of prostate cancer progression even after resistance to existing therapies develops.

Current AR-targeted treatments often lose effectiveness within 18 months due to AR amplifications, mutations, or splicing variants. SHR3591 addresses these challenges by demonstrating powerful activity against both wildtype AR and a range of clinically relevant AR mutations. Preclinical studies show SHR3591 achieves strong AR degradation at nanomolar concentrations and displays excellent selectivity, sparing other proteins commonly affected by CRBN-targeting drugs.

In animal models, SHR3591 induced over 90% AR degradation and robust tumor regression without notable side effects, and it exhibited favorable pharmacokinetics with good oral bioavailability. Now moving toward Phase 1/1b clinical trials, SHR3591 could become a promising new strategy for patients with advanced, treatment-resistant prostate cancer.

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