Bavdegalutamide (ARV-110) is a PROTAC degrader of androgen receptor (AR). Bavdegalutamide can be used in studies about prostate cancer. Bavdegalutamide shows oral activity and selectivity and facilitates the ubiquitination and degradation of AR.

Bavdegalutamide effectively degrades AR in all tested cell lines, achieving a 50% degradation concentration (DC50) of <1 nM[1]. In LNCaP cells, Bavdegalutamide induces dose-dependent AR degradation within the concentration range of 0.01 nM to 300 nM[1]. In VCaP cells, a time-dependent AR degradation is observed when treated with Bavdegalutamide at 10 nM for durations ranging from 0.5 to 24 hours[1]. Treatment with Bavdegalutamide at concentrations between 10 nM and 1000 nM results in the suppression of AR-target gene PSA expression, inhibition of AR-dependent cell proliferation, and induction of apoptosis at low nanomolar concentrations[1]. Bavdegalutamide effectively degrades clinically relevant mutant AR proteins (WT AR, F876L, T877A, M896V, and H874V) and maintains activity in a high androgen environment (R1881, 100 nM) in VCaP cells[1].

Administered through oral gavage at a dose of 1 mg/kg once daily, Bavdegalutamide demonstrates over 90% AR degradation in vivo. In LNCaP, VCaP, and patient-derived xenograft (PDX) models of prostate cancer, Bavdegalutamide significantly inhibits tumor growth and AR signaling[1]. In a long-term, castrate, enzalutamide-resistant VCaP tumor model, oral gavage of Bavdegalutamide at doses of 3 or 10 mpk for 30 days shows in vivo efficacy and reduces AR-target gene expression. The tumor growth inhibition (TGI) is 70% and 60% for 3 mg/kg and 10 mg/kg dosages, respectively[1].