biostudies-literatureLoddick SAMedical Research Council1715-27https://www.ebi.ac.uk/biostudies/studies/S-EPMC3769207biostudies-literatureUnknown12(9)Continued androgen receptor (AR) expression and signaling is a key driver in castration-resistant prostate cancer (CRPC) after classical androgen ablation therapies have failed, and therefore remains a target for the treatment of progressive disease. Here, we describe the biological characterization of AZD3514, an orally bioavailable drug that inhibits androgen-dependent and -independent AR signaling. AZD3514 modulates AR signaling through two distinct mechanisms, an inhibition of ligand-driven nuclear translocation of AR and a downregulation of receptor levels, both of which were observed in vitro and in vivo. AZD3514 inhibited testosterone-driven seminal vesicle development in juvenile male rats and the growth of androgen-dependent Dunning R3327H prostate tumors in adult rats. FurthermorMolecular cancer therapeuticsAZD3514: a small molecule that modulates androgen receptor signaling and function in vitro and in vivo.PMC3769207G0800889G0800889/1G0900871Robinson DMGaughan LWomack CWilson JBroadbent NLoddick SACritchlow SEBrooks ANThomason AGBarry STBrave SRBradbury RHJacobs VNRabow ARobson CNMouchet EWalker GERoss SJShaheen FSStratton NCTrueman DCumberbatch MWedge SRJones RDDunkley TPfalseAZD3514: a small molecule that modulates androgen receptor signaling and function in vitro and in vivo.Continued androgen receptor (AR) expression and signaling is a key driver in castration-resistant prostate cancer (CRPC) after classical androgen ablation therapies have failed, and therefore remains a target for the treatment of progressive disease. Here, we describe the biological characterization of AZD3514, an orally bioavailable drug that inhibits androgen-dependent and -independent AR signaling. AZD3514 modulates AR signaling through two distinct mechanisms, an inhibition of ligand-driven nuclear translocation of AR and a downregulation of receptor levels, both of which were observed in vitro and in vivo. AZD3514 inhibited testosterone-driven seminal vesicle development in juvenile male rats and the growth of androgen-dependent Dunning R3327H prostate tumors in adult rats. Furthermor2013-01-01T00:00:00Z2013 Sep2025-04-19T11:23:48.138Z2019-03-27T01:15:47ZS-EPMC37692072386134710.1158/1535-7163.MCT-12-117410.1158/1535-7163.mct-12-1174