preferably FXXFL motifs) A ligand dependent nuclear export signal F) – C-terminal domain Splice variants AR-V7 is an androgen receptor splice variant that can be detected in circulating tumor cells of metastatic prostate cancer patients and is predictive of resistance to some drugs. Clinical significance High expression in androgen receptor has been linked to aggression and sex drive by affecting the HPA and HPG axis Aberrant androgen receptor coregulator activity may contribute to the progression of prostate cancer. Ligands Agonists Endogenous androgens (e.g., testosterone, dihydrotestosterone, androstenedione, androstenediol, dehydroepiandrosterone) Synthetic androgens (e.g., methyltestosterone, metandienone, nandrolone, trenbolone, oxandrolone, stanozolol) Mixed Selective androgen receptor modulators (e.g., andarine, enobosarm) Antagonists Steroidal antiandrogens (e.g., cyproterone acetate, chlormadinone acetate, spironolactone, oxendolone) Nonsteroidal antiandrogens (e.g., flutamide, nilutamide, bicalutamide, enzalutamide, apalutamide, RU-58841) N-Terminal domain antiandrogens (e.g., bisphenol A, EPI-001, ralaniten, JN compounds) As a drug target The AR is an important therapeutic target in prostate cancer. Thus many different antiandrogens have been developed, primarily targeting the ligand-binding domain of the protein. AR ligands can either be classified based on their structure (steroidal or nonsteroidal) or based on their ability to activate or inhibit transcription (agonists or antagonists). Inhibitors that target alternative functional domains (N-terminal domain, DNA-binding domain) of the protein are still under development. Drug resistance Alteration of ARs may lead to treatment resistance (castration resistance) in prostate cancer as there may be missense mutations of the ligand binding domain, amplifications of the gene coding for this receptor or in its enhancer, mostly, suggesting the presence of different subclones with different genotypes of these receptors. Interactions Androgen receptor has been shown to interact with: AKT1, BAG1, Beta-catenin, BRCA1, C-jun, Calmodulin 1, Caveolin 1, CDK9, COX5B, CREB-binding protein, Cyclin D1, Cyclin-dependent kinase 7, DACH1, Death associated protein 6, L-DOPA, EFCAB6, Epidermal growth factor receptor, FOXO1, GAPDH, Gelsolin, GNB2L1, GSK3B, HDAC1, HSP90AA1, HTATIP, MAGEA11, MED1, MYST2, NCOA1, NCOA2, NCOA3, NCOA4, NCOA6, NCOR2, NONO, p300, PA2G4, PAK6, PATZ1, PIAS2, PRPF6, PTEN, RAD9A, RANBP9, RCHY1, Retinoblastoma protein, RNF14, RNF4, SART3, SIRT1, SMAD3, Small heterodimer partner, Src, SRY, STAT3, SVIL, Testicular receptor 2, Testicular receptor 4, TGFB1I1, TMF1, TRIM68, UBE2I, UXT, and ZMIZ1. See also Membrane androgen receptor Discovery and development of antiandrogens References External links GeneReviews/NCBI/NIH/UW entry on Androgen Insensitivity Syndrome OMIM entries on Androgen Insensitivity Syndrome GeneReviews/NIH/NCBI/UW entry on Spinal and Bulbar Muscular Atrophy, Kennedy's Disease, SBMA, X-Linked Spinal and Bulbar Muscular Atrophy OMIM entries on Spinal and Bulbar Muscular Atrophy,