Discovery of antiandrogen activity of nonsteroidal scaffolds of marketed drugs.

ABSTRACT: Finding good drug leads de novo from large chemical libraries, real or virtual, is not an easy task. High-throughput screening is often plagued by low hit rates and many leads that are toxic or exhibit poor bioavailability. Exploiting the secondary activity of marketed drugs, on the other hand, may help in generating drug leads that can be optimized for the observed side-effect target, while maintaining acceptable bioavailability and toxicity profiles. Here, we describe an efficient computational methodology to discover leads to a protein target from safe marketed drugs. We applied an in silico "drug repurposing" procedure for identification of nonsteroidal antagonists against the human androgen receptor (AR), using multiple predicted models of an antagonist-bound receptor. The library of

SUBMITTER: Bisson WH 

PROVIDER: S-EPMC1924583 | biostudies-literature | 2007 Jul

REPOSITORIES: biostudies-literature