Authors
Matthieu Schapira, Bruce M Raaka, Herbert H Samuels, Ruben Abagyan
Publication date
2000/2/1
Journal
Proceedings of the National Academy of Sciences
Volume
97
Issue
3
Pages
1008-1013
Publisher
The National Academy of Sciences
Description
Nuclear hormone receptors (NRs) are potential targets for therapeutic approaches to many clinical conditions, including cancer, diabetes, and neurological diseases. The crystal structure of the ligand binding domain of agonist-bound NRs enables the design of compounds with agonist activity. However, with the exception of the human estrogen receptor-α, the lack of antagonist-bound “inactive” receptor structures hinders the rational design of receptor antagonists. In this study, we present a strategy for designing such antagonists. We constructed a model of the inactive conformation of human retinoic acid receptor-α by using information derived from antagonist-bound estrogen receptor-α and applied a computer-based virtual screening algorithm to identify retinoic acid receptor antagonists. Thus, the currently available crystal structures of NRs may be used for the rational design of antagonists, which could lead to …
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Scholar articles
M Schapira, BM Raaka, HH Samuels, R Abagyan - Proceedings of the National Academy of Sciences, 2000