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

被引：37

作者：

Doddareddy, Munikumar Reddy

Choo, Hyunah

Cho, Yong Seo

Rhim, Hyewhon

Koh, Hun Yeong

Lee, Jung-Ha

Jeong, Seong-Woo

Pae, Ae Nim

机构：

[1] Korea Inst Sci & Technol, Div Life Sci, Seoul 130650, South Korea

[2] Sogang Univ, Dept Life Sci, Seoul 121742, South Korea

[3] Yonsei Univ, Wonju Coll Med, Dept Physiol, Wonju 220701, Kangwon Do, South Korea

来源：

BIOORGANIC & MEDICINAL CHEMISTRY | 2007年 / 15卷 / 02期

关键词：

virtual screening; pharmacophore; T-type calcium channel blockers;

D O I：

10.1016/j.bmc.2006.10.013

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

071010 ; 081704 ;

摘要：

Virtual screening of the commercial databases was done by using a three dimensional pharmacophore previously developed for T-type calcium channel blockers using CATALYST (TM) program. Biological evaluation of 25 selected virtual hits resulted in the discovery of a highly potent compound VH04 with IC50 value of 0.10 mu M, eight times as potent as the known selective T-type calcium channel blocker, mibefradil. Search for similar compounds yielded several hits with micro-molar IC50 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. (c) 2006 Elsevier Ltd. All rights reserved.

引用

页码：1091 / 1105

页数：15

共 24 条

[1] Calcium-antagonist drugs [J].