Nonsteroidal SARMs

The vast majority of SARMs that have been reported are nonsteroidal. Notable exceptions are a series of Merck patents (see above) and MENT [229]. Thus, it can be expected that many of the pharmacokinetic (what the body does to the drug absorption, distribution, metabolism and excretion) and pharmacodynamic (what the drug does to the body pharmacologic, phenotypic and toxicologic effects) problems inherent to the steroid nucleus may be absent in SARMs. Pharmacokinetic/pharmacodynamic profiles have been published for a number of nonsteroidal SARMs [230]. 

Table 8.1 Pharmacokinetics and pharmacodynamics of nonsteroidal SARMs vs. traditional steroidal androgens.

Brown TR. Nonsteroidal selective androgen receptors modulators (SARMs) designer androgens with flexible structures provide clinical promise. Endocrinology 2004 145 5417-5419. 

Although the traditional steroidal agonists and nonsteroidal antagonists are used for a narrow spectrum of diseases (owing to the factors discussed in Section 8.2.1), these molecules have served as archetypical scaffolds (generalized structural templates) for the development of many other related AR chemotypes with potentially broad therapeutic application. Over 64 chemically distinct putative AR agonist templates have been reported, including 22 templates with demonstrated in vivo tissue-selectivity for anabolic tissues [i.e. selective AR modulators (SARMs)]. 

T., Miyakawa, M., Amano, S., Sumita, Y. and Oguro, N. (2003) Bone anabolic effects of S-40503, a novel nonsteroidal selective androgen receptor modulator (SARM), in rat models of osteoporosis. Biological e[ Pharmaceutical Bulletin, 26, 1563-1569. 

Ke, H.Z., Crawford, D.T., Oi, H. et al. (1-5 October 2004) A novel, nonsteroidal selective androgen receptor modulator (SARM) increases periosteal bone formation and inhibits trabecular bone turnover in aged intact and orchidectomized male rats, 26th Annual Meeting of the American Society for Bone and Mineral Research, abstract 1216. 

Han, B., Triantafillou, J.A., Shen, Y., Xu, T., Scates, P., Stimpson, S.A. and Turnbull, P.S. (2-5 June 2007) Pharmacological profiles of GSK2420A, a novel nonsteroidal selective androgen receptor modulator (SARM), Endocrine... 

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