A new patented technology for drug discovery based upon gene structure utilizes the discovery of stereochemical relationships between small biologically active ligands and specific unwound DNA sequences to create pharmacophores for drug design. The estrogen gene pharmacophore was used to design a new estrogen PDC-7 which as predicted was more estrogenic (2-3 times) in classical 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 support the hypothesis that receptor assisted insertion of ligand into DNA is a mode of action of certain gene regulatory pharmaceuticals and provide powerful tool for new drug design.
|Original language||English (US)|
|Number of pages||16|
|Journal||Medicinal Chemistry Research|
|Publication status||Published - Dec 1 2001|
ASJC Scopus subject areas
- Pharmacology, Toxicology and Pharmaceutics(all)
- Organic Chemistry