Virtual Screening for Ligands of the Insect Molting Hormone Receptor

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...

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Bibliographic Details
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
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Summary: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.
ISSN:1549-9596
1549-960X
DOI:10.1021/ci100400k