title: Structures of androgen receptor bound with ligands: advancing understanding of biological functions and drug discovery.
abstract: BACKGROUND
  Androgen receptor (AR) is a ligand-dependent transcription factor and a member of the nuclear receptor superfamily. It plays a vital role in male sexual development and regulates gene expression in various tissues, including prostate. Androgens are compounds that exert their biological effects via interaction with AR. Binding of androgens to AR initiates conformational changes in AR that affect binding of co-regulator proteins and DNA. AR agonists and antagonists are widely used in a variety of clinical applications (i.e. hypogonadism and prostate cancer therapy).
  
  
  METHODS
  This review provides a close look at structures of AR-ligand complexes and mutations in the receptor that have been revealed, discusses current challenges in the field, and sheds light on future directions.
  
  
  CONCLUSIONS
  AR is one of the primary targets for the treatment of prostate cancer, as AR antagonists inhibit prostate cancer growth. However, these drugs are not effective for long-term treatment and lead to castration-resistant prostate cancer. The structures of AR-ligand complexes are an invaluable scientific asset that enhances our understanding of biological functions and mechanisms of androgenic and anti-androgenic chemicals as well as promotes the discovery of superior drug candidates.
authors.affiliation: a Division of Bioinformatics and Biostatistics , National Center for Toxicological Research, U.S. Food and Drug Administration , Jefferson , AR , USA.
authors.forename: Sugunadevi
authors.initials: S
authors.lastname: Sakkiah
authors.affiliation: a Division of Bioinformatics and Biostatistics , National Center for Toxicological Research, U.S. Food and Drug Administration , Jefferson , AR , USA.
authors.forename: Hui Wen
authors.initials: HW
authors.lastname: Ng
authors.affiliation: a Division of Bioinformatics and Biostatistics , National Center for Toxicological Research, U.S. Food and Drug Administration , Jefferson , AR , USA.
authors.forename: Weida
authors.initials: W
authors.lastname: Tong
authors.affiliation: a Division of Bioinformatics and Biostatistics , National Center for Toxicological Research, U.S. Food and Drug Administration , Jefferson , AR , USA.
authors.forename: Huixiao
authors.initials: H
authors.lastname: Hong
mesh_terms: D059002:Androgen Receptor Antagonists / Q000494:pharmacology / Q000627:therapeutic use*; D000728:Androgens / Q000378:metabolism* / Q000494:pharmacology; D015195:Drug Design; D055808:Drug Discovery; D006801:Humans; D007006:Hypogonadism / Q000188:drug therapy / Q000473:pathology; D008024:Ligands; D008297:Male; D011471:Prostatic Neoplasms / Q000188:drug therapy / Q000473:pathology; D011944:Receptors, Androgen / Q000187:drug effects* / Q000378:metabolism
chemical_list: D059002:Androgen Receptor Antagonists; D000728:Androgens; D008024:Ligands; D011944:Receptors, Androgen
keywords: Androgen receptor; dihydrotestosterone; endocrine disruptors; endocrine receptor; testosterone