Inhibitors of aspartic proteases in human diseases: molecular modeling comes of age.

The family of aspartic proteases such as cathepsin D, gastricin, pepsin, renin, HIV protease and others have been the subject of molecular modeling in the field of drug design in the last years. The first aspartic protease inhibitor was reported thirty years ago as a renin inhibitor. The success of HIV protease inhibitors in preventing progression to AIDS was based on the transition state analogs of renin inhibitors. Taking these three decades into consideration, an astonishing variety of chemical classes, in vitro and in vivo activities and species specificities of inhibitors of aspartic proteases have been reported. Especially inhibitors of renin, HIV protease and secreted aspartic protease of Candida albicans are covered.