3D pharmacophore based virtual screening of T-type calcium channel blockers.

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Doddareddy MR, Choo H, Cho YS, Rhim H, Koh HY, Lee JH, Jeong SW, Pae AN

3D pharmacophore based virtual screening of T-type calcium channel blockers.

Bioorg Med Chem. 2007 Jan 15;15(2):1091-105. Epub 2006 Oct 30.

PubMed ID

17074493 [ View in PubMed

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Abstract

Virtual screening of the commercial databases was done by using a three dimensional pharmacophore previously developed for T-type calcium channel blockers using CATALYSTtrade mark program. Biological evaluation of 25 selected virtual hits resulted in the discovery of a highly potent compound VH04 with IC(50) value of 0.10 microM, eight times as potent as the known selective T-type calcium channel blocker, mibefradil. Search for similar compounds yielded several hits with micro-molar IC(50) values and high T-type calcium channel selectivity. Based on the structure of the virtual hits, small molecule libraries with novel scaffolds were designed, synthesis and biological evaluation of which are currently in progress. This result shows a successful example of ligand based drug discovery of potent T-type calcium channel blockers.

DrugBank Data that Cites this Article

Binding Properties

Drug	Target	Property	Measurement	pH	Temperature (°C)
Mibefradil	Voltage-dependent T-type calcium channel subunit alpha-1G	IC 50 (nM)	840	N/A	N/A	Details