Journal of Medicinal Chemistry · 2004 · 24 citations · 13 references
PharmacyMedicinal ChemistryPharmacologyDrug DesignDrug DiscoveryStructure-activity RelationshipsEndocrine PharmacologyGrowth HormoneHormone StructureLigand BindingReceptor PharmacologyStructure-activity Relationship AnalysisAgonist ActivityBinding AssaysGrowth Hormone Binding AssaysGrowth Hormone ReceptorsGrowth Hormone StructureRadioligand Binding AssaysReceptor Binding AssaysVirtual Screening Validation
Two molecules with known growth hormone secretagogue (GHS) agonist activity were used as templates to computationally screen approximately 80000 compounds. A total of 108 candidate compounds were selected, and five of them were found to be active in the low-micromolar range in both cell-based and direct binding assays. These compounds were structurally diverse and significantly differed from known GHS agonists. The most active compound was subjected to SAR evaluation, which slightly increased its potency and identified molecular regions important for specific GHS agonist activity.
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