title: Coactivators in assay design for nuclear hormone receptor drug discovery.
abstract: Nuclear hormone receptors (NHRs) represent one of the most important drug targets in terms of therapeutic applications. The NHR superfamily consists of a family of DNA binding transcription factors whose function can be controlled by small molecules (steroids or organic acids). Therefore, NHRs are suitable protein targets for the therapies of human diseases. Some of the current marketed drugs, including several anticancer and antidiabetic drugs, are known to target NHRs. Examples include the anticancer and retinoid X receptor-targeting Targretin and the antidiabetic and peroxisome proliferative-activated receptor-gamma-targeting thiaozolidinediones. More NHR-targeting drugs are expected in the coming years. Identification of specific NHR modulators, as well as identification of ligands for orphan NHRs, will lead to new therapies for many human diseases. Many pharmaceutical companies are investing in NHR-targeted drugs, which are estimated to be 10-15% of the US dollars 400 billion global pharmaceutical market. This minireview discusses various aspects of NHR drug discovery, with a focus on the application of NHR coactivators in assay design for NHR ligand identification.
authors.affiliation: Lead Discovery and Profiling, Bristol-Myers Squibb Company, Wallingford, CT 06492, USA. taosheng.chen@bms.com
authors.forename: Taosheng
authors.initials: T
authors.lastname: Chen
authors.forename: Wen
authors.initials: W
authors.lastname: Xie
authors.forename: Michele
authors.initials: M
authors.lastname: Agler
authors.forename: Martyn
authors.initials: M
authors.lastname: Banks
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D016503:Drug Delivery Systems / Q000379:methods*; D006801:Humans; D008969:Molecular Sequence Data; D018160:Receptors, Cytoplasmic and Nuclear / Q000737:chemistry / Q000235:genetics* / Q000378:metabolism*; D013678:Technology, Pharmaceutical / Q000379:methods
chemical_list: D018160:Receptors, Cytoplasmic and Nuclear