Development of selective androgen receptor modulators (SARMs)

Narayanan, Ramesh; Coss, Christopher C.; Dalton, James T.

doi:10.1016/j.mce.2017.06.013

Cited by 253Hormonal and reproductive studiesProstate Cancer Treatment and ResearchEstrogen and related hormone effects

Development of selective androgen receptor modulators (SARMs)

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Narayanan, Ramesh, Coss, Christopher C., Dalton, James T.·2018·Molecular and Cellular Endocrinology

DOI 10.1016/j.mce.2017.06.013PMC PMC5896569

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Abstract

The Androgen Receptor (AR), a member of the steroid hormone receptor family, plays important roles in the physiology and pathology of diverse tissues. AR ligands, which include circulating testosterone and locally synthesized dihydrotestosterone, bind to and activate the AR to elicit their effects. Ubiquitous expression of the AR, metabolism and cross reactivity with other receptors limit broad therapeutic utilization of steroidal androgens. However, the discovery of selective androgen receptor modulators (SARMs) and other tissue-selective nuclear hormone receptor modulators that activate their cognate receptors in a tissue-selective manner provides an opportunity to promote the beneficial effects of androgens and other hormones in target tissues with greatly reduced unwanted side-effects. In the last two decades, significant resources have been dedicated to the discovery and biological characterization of SARMs in an effort to harness the untapped potential of the AR. SARMs have been proposed as treatments of choice for various diseases, including muscle-wasting, breast cancer, and osteoporosis. This review provides insight into the evolution of SARMs from proof-of-concept agents to the cusp of therapeutic use in less than two decades, while covering contemporary views of their mechanisms of action and therapeutic benefits.

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Enobosarm is a selective androgen receptor modulator (SARM).
“Steiner introduced Enobosarm, Veru's investigational selective androgen receptor modulator (SARM) [30, 31].”
From Muscle Loss in Obesity Therapy as a Therapeutic Target: Trial Design and Endpoints for Regulatory Discussions (2025) · cites this paper as [30]
Putative mechanisms of SARM selectivity include tissue-specific enzymes, modulated recruitment of coregulators, and activation of unique subcellular signaling cascades.
“Putative mechanisms of SARM selectivity include tissue specific enzymes, modulated recruitment of coregulators and activation of unique subcellular signaling cascades are some of the putative mechanisms of SARM selectivity, 249 but more research is required to understand these mechanisms and then leverage these unique features to generative more efficacious therapeutics.”
From The role of the androgen receptor in the pathogenesis of obesity and its utility as a target for obesity treatments (2022) · cites this paper as [249]

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Authors: Narayanan, R., Coss, C. C., & Dalton, J. T.
Affiliations: University of Tennessee Health Science Center (US)
The Ohio State University (US)
University of Michigan (US)
Corresponding author: Dalton, James T.
ORCID: Narayanan, Ramesh
Coss, Christopher C.
Dalton, James T.
Venue: Molecular and Cellular Endocrinology
Publisher: Elsevier BV
Published: 2018-04
Volume: 465
Pages: 134-142
ISSN: 0303-7207 (ISSN-L)
DOI: 10.1016/j.mce.2017.06.013
PMC: PMC5896569
OpenAlex: W2625829876
Cited by: 251
References: 119
Citations by year: 2026: 17 · 2025: 22 · 2024: 19 · 2023: 38 · 2022: 42 · 2021: 37 · 2020: 27 · 2019: 24 · 2018: 21 · 2017: 3 · 2016: 1
FWCI: 3.00
Type: journal article
Language: en
Open access: green
www.ncbi.nlm.nih.gov
Licence: www.elsevier.com/tdm/userlicense/1.0/ (tdm)
Locations: Molecular and Cellular Endocrinology (publishedVersion)
PubMed (publishedVersion)
Europe PMC (PubMed Central) (acceptedVersion)
PubMed Central (acceptedVersion)
Funders: National Cancer Institute (K12CA133250)
Topics: Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Hormonal and reproductive studies
Health Sciences › Medicine › Pulmonary and Respiratory Medicine › Prostate Cancer Treatment and Research
Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Estrogen and related hormone effects
Keywords: selective androgen receptor modulators, androgen receptor, testosterone, dihydrotestosterone, muscle atrophy, breast cancer, osteoporosis, mechanism of action, drug development
MeSH terms: Androgens, Animals, Humans, Models, Biological, Organ Specificity, Receptors, Androgen

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