Gene based pharmacophores for drug design

A new patented technology for drug discovery based upon gene structure util izes the discovery of stereochemical relationships between small biological ly active ligands and specific unwound DNA sequences to create pharmacophor es for drug design. The estrogen gene pharmacophore was used to design a ne w estrogen PDC-7 which as predicted was more estrogenic (2-3 times) in clas sical in vivo assays than the natural hormone estradiol. Poor fit of PDC-7 into the estrogen receptor protein pharmacophore explained poor binding (15 -18%) to the estrogen receptor relative to estradiol. These findings suppor t the hypothesis that receptor assisted insertion of ligand into DNA is a m ode of action of certain gene regulatory pharmaceuticals and provide powerf ul tool for new drug design.