title: Virtual screening for ligands of the insect molting hormone receptor.
abstract: Insect growth is regulated by the orchestrated event of ecdysteroids and their receptor proteins. Agonists/antagonists of ecdysteroid receptor are predicted to disrupt normal growth, providing good candidates of new insecticides. A database of over 2 million compounds was subjected to a shape-based virtual screening cascade to identify novel nonsteroidal hits similar to the known EcR ligand ponasterone A. Testing revealed micromolar hits against two strains of insect cells. Docking experiments against EcR were used to support the predicted binding mode of these ligands based on their overlay to ponasterone A.
authors.affiliation: Graduate School of Agriculture, Division of Applied Life Sciences, Kyoto University, Sakyo-ku, Kyoto, Japan.
authors.forename: Toshiyuki
authors.initials: T
authors.lastname: Harada
authors.forename: Yoshiaki
authors.initials: Y
authors.lastname: Nakagawa
authors.forename: Takehiko
authors.initials: T
authors.lastname: Ogura
authors.forename: Yutaka
authors.initials: Y
authors.lastname: Yamada
authors.forename: Takehiro
authors.initials: T
authors.lastname: Ohe
authors.forename: Hisashi
authors.initials: H
authors.lastname: Miyagawa
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D002460:Cell Line; D019295:Computational Biology; D016208:Databases, Factual; D004331:Drosophila melanogaster / Q000235:genetics; D015195:Drug Design; D004353:Drug Evaluation, Preclinical / Q000379:methods*; D004440:Ecdysone / Q000819:agonists / Q000378:metabolism; D004441:Ecdysterone / Q000031:analogs & derivatives / Q000737:chemistry / Q000378:metabolism / Q000494:pharmacology; D017930:Genes, Reporter / Q000235:genetics; D055551:HSP27 Heat-Shock Proteins / Q000235:genetics; D019476:Insect Proteins / Q000737:chemistry / Q000378:metabolism*; D008024:Ligands; D008958:Models, Molecular; D008969:Molecular Sequence Data; D011487:Protein Conformation; D011987:Receptors, Steroid / Q000737:chemistry / Q000378:metabolism*; D015203:Reproducibility of Results; D018411:Spodoptera; D014584:User-Computer Interface
chemical_list: D055551:HSP27 Heat-Shock Proteins; D019476:Insect Proteins; D008024:Ligands; D011987:Receptors, Steroid; C055469:ecdysone receptor; D004440:Ecdysone; D004441:Ecdysterone; C008999:ponasterone A