Comparative pharmacophore development for inhibitors of human and rat 5-alpha-reductase.

There are a number of diseases where the 5-alpha-reductase (5AR) enzyme is of therapeutic interest as a drug target. Currently the crystal structure for 5-alpha-reductase is unavailable, thus ligand-based pharmacophore techniques are beneficial in the drug development process. We have developed pharmacophores to aid inhibitor design for both human types I (preliminary) and II 5-alpha-reductase isozymes and also the rat type II isozyme. To our knowledge, these are the first published pharmacophores for inhibitors of the human type I and rat type II enzymes. A comparison between isozymes and the previously published human type II isozyme pharmacophore is also presented.