Non-Steroidal Steroid Receptor Modulators

Buijsman, Rogier C.; Hermkens, Pedro H. H.; Rijn, Rachel D. van; Stöck, H; Teerhuis, N. Miranda

doi:10.2174/0929867053764671

Cited by 45 publications

(19 citation statements)

References 40 publications

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“…Similarly, and despite the fact that androgens have beneficial effects on bone and muscle mass, their negative impact on the prostate prevents their widespread use in the treatment of osteoporosis and frailty in males (20). This dual and important medical need has led to the development of several SERMs and the marketing of some (1,5,8) as well as the search for selective androgen receptor modulators (SARMs), some of which are currently in preclinical or clinical development (21,22).…”

Section: Discussionmentioning

confidence: 99%

Bone protection by estrens occurs through non–tissue-selective activation of the androgen receptor

Windahl

Galien²,

Chiusaroli³

et al. 2006

J. Clin. Invest.

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The use of estrogens and androgens to prevent bone loss is limited by their unwanted side effects, especially in reproductive organs and breast. Selective estrogen receptor modulators (SERMs) partially avoid such unwanted effects, but their efficacy on bone is only moderate compared with that of estradiol or androgens. Estrens have been suggested to not only prevent bone loss but also exert anabolic effects on bone while avoiding unwanted effects on reproductive organs. In this study, we compared the effects of a SERM (PSK3471) and 2 estrens (estren-α and estren-β) on bone and reproductive organs to determine whether estrens are safe and act via the estrogen receptors and/or the androgen receptor (AR). Estrens and PSK3471 prevented gonadectomy-induced bone loss in male and female mice, but none showed true anabolic effects. Unlike SERMs, the estrens induced reproductive organ hypertrophy in both male and female mice and enhanced MCF-7 cell proliferation in vitro. Estrens directly activated transcription in several cell lines, albeit at much higher concentrations than estradiol or the SERM, and acted for the most part through the AR. We conclude that the estrens act mostly through the AR and, in mice, do not fulfill the preclinical efficacy or safety criteria required for the treatment or prevention of osteoporosis.

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Section: Discussionmentioning

confidence: 99%

Bone protection by estrens occurs through non–tissue-selective activation of the androgen receptor

Windahl

Galien²,

Chiusaroli³

et al. 2006

J. Clin. Invest.

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“…The latest developments in nonsteroidal AR ligands have been extensively reviewed in last five years, including the structural biology and structure-activity relationships (1), medicinal chemistry (2), and potential clinical applications (3). This review focuses on the in vivo pharmacokinetic and pharmacologic properties of nonsteroidal AR ligands, including antagonists, agonists, and selective androgen receptor modulators (SARMs).…”

Section: Introductionmentioning

confidence: 99%

Pharmacokinetics and Pharmacodynamics of Nonsteroidal Androgen Receptor Ligands

2006

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Testosterone and structurally related anabolic steroids have been used to treat hypogonadism, muscle wasting, osteoporosis, male contraception, cancer cachexia, anemia, and hormone replacement therapy in aging men or age-related frailty; while antiandrogens may be useful for treatment of conditions like acne, alopecia (male-pattern baldness), hirsutism, benign prostatic hyperplasia (BPH) and prostate cancer. However, the undesirable physicochemical and pharmacokinetic properties of steroidal androgen receptor (AR) ligands limited their clinical use. Nonsteroidal AR ligands with improved pharmacological and pharmacokinetic properties have been developed to overcome these problems. This review focuses on the pharmacokinetics, metabolism, and pharmacology of clinically used and emerging nonsteroidal AR ligands, including antagonists, agonists, and selective androgen receptor modulators.

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“…aspects of the SAR and biological activities of compounds in this class [4]. A summary of those studies and highlighted specific examples from each chemical series are described below.…”

Section: Quinolone and Coumarin Derivativesmentioning

confidence: 99%

“…Recent peer-reviewed and patent publications have disclosed SARMs with improved pharmacokinetic properties and tissue selective activity. A handful of excellent reviews on non-steroidal AR ligands have been published [2][3][4][5][6][7][8][9]. This review will provide a comprehensive overview of the SARM literature up to August 2005 and will put particular emphasis on the therapeutic potential of this exciting class of molecules.…”

Section: Introductionmentioning

confidence: 99%

Selective Androgen Receptor Modulators in Drug Discovery: Medicinal Chemistry and Therapeutic Potential

Cadilla¹,

Turnbull²

2006

CTMC

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Modulation of the androgen receptor has the potential to be an effective treatment for hypogonadism, andropause, and associated conditions such as sarcopenia, osteoporosis, benign prostatic hyperplasia, and sexual dysfunction. Side effects associated with classical anabolic steroid treatments have driven the quest for drugs that demonstrate improved therapeutic profiles. Novel, non-steroidal compounds that show tissue selective activity and improved pharmacokinetic properties have been developed. This review provides an overview of current advances in the development of selective androgen receptor modulators (SARMs).

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Non-Steroidal Steroid Receptor Modulators

Cited by 45 publications

References 40 publications

Bone protection by estrens occurs through non–tissue-selective activation of the androgen receptor

Bone protection by estrens occurs through non–tissue-selective activation of the androgen receptor

Pharmacokinetics and Pharmacodynamics of Nonsteroidal Androgen Receptor Ligands

Selective Androgen Receptor Modulators in Drug Discovery: Medicinal Chemistry and Therapeutic Potential

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