Virtual Screening for Ligands of the Insect Molting Hormone Receptor

• Published in: Journal of chemical information and modeling 2011-02, Vol.51 (2), p.296-305
• Main Authors: Harada, Toshiyuki, Nakagawa, Yoshiaki, Ogura, Takehiko, Yamada, Yutaka, Ohe, Takehiro, Miyagawa, Hisashi
• Format: Article
• Language: English
• Subjects: Amino Acid Sequence; Animals; Binding sites; Biochemistry; Biological and medical sciences; Cell Line; Cells; Chemistry; Computational Biology; Computational Chemistry; Databases, Factual; Drosophila melanogaster - genetics; Drug Design; Drug Evaluation, Preclinical - methods; Ecdysone - agonists; Ecdysone - metabolism; Ecdysterone - analogs & derivatives; Ecdysterone - chemistry; Ecdysterone - metabolism; Ecdysterone - pharmacology; Exact sciences and technology; General and physical chemistry; General pharmacology; General. Nomenclature, chemical documentation, computer chemistry; Genes, Reporter - genetics; HSP27 Heat-Shock Proteins - genetics; Insect Proteins - chemistry; Insect Proteins - metabolism; Insecticides; Insects; Ligands; Medical sciences; Models, Molecular; Molecular Sequence Data; Molecules; Pharmaceutical technology. Pharmaceutical industry; Pharmacology. Drug treatments; Protein Conformation; Proteins; Receptors, Steroid - chemistry; Receptors, Steroid - metabolism; Reproducibility of Results; Spodoptera; Theory of reactions, general kinetics. Catalysis. Nomenclature, chemical documentation, computer chemistry; User-Computer Interface
• ISSN: 1549-9596; 1549-960X
• DOI: 10.1021/ci100400k

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.