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

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

  • Bioorg Med Chem. 2007 Jan 15;15(2):1091-105. doi: 10.1016/j.bmc.2006.10.013.
Munikumar Reddy Doddareddy 1,  Hyunah Choo,  Yong Seo Cho,  Hyewhon Rhim,  Hun Yeong Koh,  Jung-Ha Lee,  Seong-Woo Jeong,  Ae Nim Pae
Affiliations

Affiliation

  • 1 Life Science Division, Korea Institute of Science and Technology, PO Box 131, Cheongryang, Seoul 130-650, Republic of Korea.
PMID: 17074493 DOI: 10.1016/j.bmc.2006.10.013
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.

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