Pharmacophore Models as Part of a Multi-step Screening Approach

1 Pharmacophore Models as Part of a Multi-step Screening Approach 

Lu et u/. screened a prefiltered set of 11000 compounds from the NCI database with a pharmacophore model based on the crystal structure of murine double minute 2 (MDM2) oncoprotein in complex with the p53 tumor suppressor and several non-peptide small inhibitors. The remaining compounds were docked, scored, and 67 compounds were selected for testing, ten of which were active in a competitive binding assay. Similarly, Yu et used a Catalyst HipHop model combined with the molecular shape of an experimental X-ray 

Barreca et al screened for non-nucleoside reverse transcriptase inhibitors of HIV-1 by searching the Derwent World Drug Index (WDI) and the Chemicals Available for Purchase (CAP) databases with a Catalyst model generated by LigandScout. A Fit value cutoff of 3.0 and Lipinski filters, followed by docking, led to the selection of three compounds, two of which were commercially available. A search for available close analogues of all three compounds finally led to the purchase of six compounds, of which five were shown to be active. 

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