Ockham's razor and selective androgen receptor modulators (SARMs): are we overlooking the role of 5alpha-reductase?
Selective Androgen Receptor Modulators (SARMs) are a novel class of AR ligands that possess tissue-selective pharmacological activities. SARMs of various chemical structures have been discovered and characterized, and lead compounds with much improved specificity for AR, in vivo pharmacokinetic profiles, and higher degree of tissue selectivity have entered clinical development, and are expected to dramatically expand the clinical applications of androgens. With the rapid progress in SARM discovery and increasing demand for mechanism-based drug design, more and more research efforts have been devoted to the mechanisms of action of the observed tissue selectivity of SARMs. There is increasing enthusiasm in adapting the molecular mechanisms of action from SERM research to the SARM field; however, is the SARM story really so complicated? The tissue-specific expression of 5alpha-reductase might provide a simple explanation for this puzzle.
Gao
Wenqing
W
Department of Pharmaceutical Sciences, School of Pharmacy, University at Buffalo SUNY, Buffalo, NY 14260, USA.
Dalton
James T
JT
D013741:3-Oxo-5-alpha-Steroid 4-Dehydrogenase / Q000378:metabolism*; D058891:5-alpha Reductase Inhibitors; D000726:Androgen Antagonists / Q000494:pharmacology*; D059002:Androgen Receptor Antagonists; D000728:Androgens / Q000494:pharmacology* / Q000502:physiology; D004791:Enzyme Inhibitors / Q000494:pharmacology*; D005260:Female; D018120:Finasteride / Q000494:pharmacology; D005544:Forecasting; D006801:Humans; D008297:Male; D011467:Prostate / Q000187:drug effects; D011470:Prostatic Hyperplasia / Q000188:drug therapy; D011944:Receptors, Androgen / Q000187:drug effects* / Q000502:physiology*; D013739:Testosterone / Q000502:physiology; D014018:Tissue Distribution
D058891:5-alpha Reductase Inhibitors; D000726:Androgen Antagonists; D059002:Androgen Receptor Antagonists; D000728:Androgens; D004791:Enzyme Inhibitors; D011944:Receptors, Androgen; D013739:Testosterone; D018120:Finasteride; D013741:3-Oxo-5-alpha-Steroid 4-Dehydrogenase