Pharmacophore Modeling for Antitargets

Khac-Minh      Thai; Trieu-Du      Ngo; Thanh-Dao      Tran; Minh-Tri      Le

doi:10.2174/1568026611313090004

Abstract

The pharmacophore modeling in modern drug research has been applied for both bioactivity profiling and early stage of risk assessment of potential side effects and toxicity due to interactions of drug candidates with antitargets namely P-glycoprotein, hERG, cytochrome P450 and pregnane X-receptor. In this article, an existing state concerning with pharmacophore modeling applied for promiscuous proteins in drug research were updated and reviewed. In an attempt to create new safe medicines faster, the partial overlap of substrate properties of hERG, P-glycoprotein, pregnane X-receptor and cytochrome P450 has to be considered and drug safety has to be dealt on a system level on the off-targets.

Keywords: Antitargets, P-glycoprotein, Human ether-a-go-go related gene, Cytochrome P450, Pregnane X-receptor, Pharmacophore modeling, hERG, P-gp, ABCB1.