Premium
New Mechanisms for Old Targets: Novel Approaches to Steroid Receptors in Drug Discovery
Author(s) -
Freedman Leonard P
Publication year - 2008
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.22.1_supplement.402.1
Subject(s) - drug discovery , estrogen receptor , receptor , hormone , signal transduction , estrogen , androgen receptor , drug development , biology , drug , steroid , androgen , pharmacology , bioinformatics , medicine , endocrinology , microbiology and biotechnology , cancer , prostate cancer , biochemistry , breast cancer
Steroid hormones such as estrogens and androgens play critical roles in normal and patho‐physiology. Through their binding to nuclear hormone receptors, they also provide attractive targets for drug discovery. Considerable effort has been exerted over the past several years in designing so‐called selective estrogen or androgen receptor modulators that recapitulate the desired effects of these steroids on specific target tissues (i.e., the inhibition of bone resorption or stimulation of bone formation), without undesired effects on other target tissues. While much progress has clearly been achieved, recent insights into the mechanisms of action of these targets provide new opportunities to generate compounds and drugs with even greater efficacy and selectivity than those that are currently being used as established therapies. For example, the activation of particular non‐genomic signal transduction cascades has been suggested to play a key role in estrogen‐induced cardio‐, neuro‐, and osteo‐protection. Therefore, the development of functionally ‐selective ER ligands may provide a novel means for preserving the beneficial effects of estrogens on nonreproductive tissues during post‐reproductive life, while minimizing or eliminating their action on reproductive tissues. The data that will be presented may lead to the development of a new generation of estrogens with superior pharmacological properties.