title: Binding capacity of ER-α ligands and SERMs: comparison of the human, dog and cat.
abstract: The estrogen molecule is the major risk factor related to mammary gland tumors, with estrogen receptor alpha (ER- α) as the important target stimulating growth. Therefore one alternative approach to treatment of breast cancer is to use selective estrogen receptor modulator (SERM), hormonal therapy. In this study, the structures of ER- α in humans, dogs and cats were predicted using the amino acid sequencing data bank and corrected for general protein structures, receptor sites and docking by adding 2,344 ligands with 15 SERMs into the database and calculating estimated inhibition constants (Ki). Thereby, ranking of best ligands of SERMs in humans, dogs and cats could be achieved. The results show that the shapes of ER- α differ between species but the major pocket sites are the same. Bazedoxifene, a new SERM proved to be the best estrogen antagonist and ER- α inhibitor in all species (human, dog, cat) with the lowest Ki. The other good ligands for dogs and cats are Neohesperidin, Dihydrochalcone, and Schreiber2. The differences in these protein structures may explain why there are only a few SERMs or other ligands which can be used as anti-cancer drugs.
authors.affiliation: Department of Pre-clinic and Applied Animal Science, Faculty of Veterinary Science, Mahidol University, Nakorn Pathom, Thailand. vsptn@mahidol.ac.th
authors.forename: Waraphan
authors.initials: W
authors.lastname: Toniti
authors.forename: Nareuthorn
authors.initials: N
authors.lastname: Suthiyotha
authors.forename: Pranom
authors.initials: P
authors.lastname: Puchadapirom
authors.forename: Ekachai
authors.initials: E
authors.lastname: Jenwitheesuk
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D000970:Antineoplastic Agents / Q000378:metabolism / Q000494:pharmacology* / Q000627:therapeutic use; D001943:Breast Neoplasms / Q000188:drug therapy / Q000378:metabolism / Q000473:pathology; D002415:Cats; D047188:Chalcones / Q000378:metabolism / Q000494:pharmacology / Q000627:therapeutic use; D004285:Dogs; D047628:Estrogen Receptor alpha / Q000037:antagonists & inhibitors / Q000737:chemistry / Q000378:metabolism*; D005260:Female; D006569:Hesperidin / Q000031:analogs & derivatives / Q000378:metabolism / Q000494:pharmacology / Q000627:therapeutic use; D006801:Humans; D007211:Indoles / Q000378:metabolism / Q000494:pharmacology / Q000627:therapeutic use; D008024:Ligands; D008321:Mammary Glands, Animal / Q000378:metabolism; D042361:Mammary Glands, Human / Q000378:metabolism; D008969:Molecular Sequence Data; D017433:Protein Structure, Secondary; D020845:Selective Estrogen Receptor Modulators / Q000737:chemistry / Q000378:metabolism* / Q000494:pharmacology* / Q000627:therapeutic use; D016415:Sequence Alignment; D020539:Sequence Analysis, Protein
chemical_list: D000970:Antineoplastic Agents; D047188:Chalcones; D047628:Estrogen Receptor alpha; D007211:Indoles; D008024:Ligands; D020845:Selective Estrogen Receptor Modulators; D006569:Hesperidin; C015812:dihydrochalcone; C546526:neohesperidin; C447119:bazedoxifene