Neklesa T, et al. - Since alterations in the androgen receptor (AR) locus has been seen in most prostate cancer patients progressing on enzalutamide or abiraterone, researchers assessed an orally bioavailable small molecule AR PROteolysis TArgeting Chimera (PROTAC) degrader, ARV-110, that promotes ubiquitination and degradation of AR. They analyzed the available data from preclinical studies that have assessed the efficacy of this molecule. Findings revealed the efficacy of ARV-110 in multiple prostate cancer models. In all cell lines tested, a strong degradation of AR by ARV-110 was seen, with an observed half-maximal degradation concentration (DC50) of about 1 nM. In proteomic studies, highly selective AR degradation by ARV-110 was reported. At a 1 mg/kg PO QD dose in mouse xenograft studies, ARV-110 led to greater than 90% AR degradation. In LNCaP, VCaP, and prostate cancer patient derived xenograft (PDX) models, marked ARV-110-induced inhibition of tumor growth and AR signaling was noted. In a long term, castrate, enzalutamide-resistant VCaP tumor model, AR-target gene expression was attenuated by ARV-110. It has also shown in vivo efficacy.