title: In silico discovery of novel retinoic acid receptor agonist structures.
abstract: BACKGROUND
  Several Retinoic Acid Receptors (RAR) agonists have therapeutic activity against a variety of cancer types; however, unacceptable toxicity profiles have hindered the development of drugs. RAR agonists presenting novel structural and chemical features could therefore open new avenues for the discovery of leads against breast, lung and prostate cancer or leukemia.
  
  
  RESULTS
  We have analysed the induced fit of the active site residues upon binding of a known ligand. The derived binding site models were used to dock over 150,000 molecules in silico (or virtually) to the structure of the receptor with the Internal Coordinates Mechanics (ICM) program. Thirty ligand candidates were tested in vitro.
  
  
  CONCLUSIONS
  Two novel agonists resulting from the predicted receptor model were active at 50 nM. One of them displays novel structural features which may translate into the development of new ligands for cancer therapy.
authors.affiliation: Structural Biology, Skirball Institute of Biomolecular Medicine, New York, USA. schapira@saturn.med.nyu.edu
authors.forename: M
authors.initials: M
authors.lastname: Schapira
authors.forename: B M
authors.initials: BM
authors.lastname: Raaka
authors.forename: H H
authors.initials: HH
authors.lastname: Samuels
authors.forename: R
authors.initials: R
authors.lastname: Abagyan
mesh_terms: D000465:Algorithms; D000970:Antineoplastic Agents / Q000737:chemistry* / Q000378:metabolism / Q000494:pharmacology; D001665:Binding Sites; D008958:Models, Molecular; D018168:Receptors, Retinoic Acid / Q000819:agonists* / Q000737:chemistry / Q000378:metabolism; D000072482:Retinoic Acid Receptor alpha
chemical_list: D000970:Antineoplastic Agents; D018168:Receptors, Retinoic Acid; D000072482:Retinoic Acid Receptor alpha; C082925:retinoic acid receptor beta