Selective androgen receptor modulator activity of a steroidal antiandrogen TSAA-291 and its cofactor recruitment profile

Hikichi, Yukiko; Yamaoka, Masuo; Kusaka, Masami; Hara, Takahito

doi:10.1016/j.ejphar.2015.08.052

Cited by 13 publications

(17 citation statements)

References 23 publications

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“…We previously reported that SARM‐2f increased skeletal muscle weight with a much lesser effect on prostate weight . The mechanisms for tissue selectivity of SARM includes two factors: recruitment of specific cofactors to AR and a tissue‐specific cofactor expression profile . We reported that SARM‐2f induced less recruitment of the protein inhibitors of the activated STATs family to the AR than did testosterone .…”

Section: Discussionmentioning

confidence: 87%

“…[15][16][17] The mechanisms for tissue selectivity of SARM includes two factors: recruitment of specific cofactors to AR and a tissue-specific cofactor expression profile. 26,27 We reported that SARM-2f induced less recruitment of the protein inhibitors of the activated STATs family to the AR than did testosterone. 16 The present study did not address TA B L E 2 Individual plasma testosterone levels in male cynomolgus monkeys before and after the indicated 4-week treatments *Reanalysis values.…”

Section: Discussionmentioning

confidence: 93%

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A selective androgen receptor modulator SARM‐2f activates androgen receptor, increases lean body mass, and suppresses blood lipid levels in cynomolgus monkeys

Morimoto

Yamaoka

Hara

2020

Pharmacology Res & Perspec

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SARM‐2f a selective androgen receptor (AR) modulator, increases skeletal muscle mass and locomotor activity in rats. This study aimed to clarify its pharmacological effects in monkeys. In reporter assays, the EC50 values of SARM‐2f for rat, monkey, and human AR were 2.5, 3, and 3.6 nmol/L, respectively; those of testosterone were 12, 3.2, and 11 nmol/L, respectively. A single oral administration (10 mg/kg SARM‐2f) produced a maximal plasma concentration of 3011 ng/mL, with an area under the 24 hours concentration‐time curve of 8152 ng·h/mL in monkeys. Body weight (BW), lean body mass (LBM), and plasma levels of total cholesterol, triglyceride, high‐density lipoprotein cholesterol, low‐density lipoprotein cholesterol, lipoprotein (a), alanine aminotransferase, and asparagine aminotransferase were measured after 4 weeks of treatment with SARM‐2f (1, 3, and 10 mg/kg/day, QD, p.o.) or testosterone enanthate (TE; 2 mg/kg/2 weeks, s.c.) in monkeys. BW and LBM were significantly increased by 12% each by SARM‐2f at 10 mg/kg, and by 5% and 8%, respectively, by TE, but these effects were not statistically significant. Plasma levels of all lipids were either decreased or showed a tendency to be decreased by SARM‐2f. TE decreased the triglyceride level and increased the low‐density lipoprotein cholesterol level. Liver marker levels were not changed by either SARM‐2f or TE. Our data demonstrated that SARM‐2f exerted anabolic effects and produced a lipid profile that differed from that produced by testosterone in monkeys, suggesting that SARM‐2f might be useful for diseases such as sarcopenia.

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Section: Discussionmentioning

confidence: 87%

Section: Discussionmentioning

confidence: 93%

A selective androgen receptor modulator SARM‐2f activates androgen receptor, increases lean body mass, and suppresses blood lipid levels in cynomolgus monkeys

Morimoto

Yamaoka

Hara

2020

Pharmacology Res & Perspec

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“…New drug entities of yet undisclosed structure were reported to possess SARM‐like properties with TSAA‐291 and ORM‐11984. While TSAA‐291 was formerly reported to exhibit predominantly antagonistic effects at androgen receptors, a more recent study with castrated mice showed agonistic properties at skeletal muscles while prostate tissue remained unaffected . ORM‐11984 was assessed as to its ability to improve bone formation when implanted as sustained‐release formulation in close proximity to the relevant location but did not prove useful in the employed setting…”

Section: Anabolic Agentsmentioning

confidence: 99%

“…While TSAA-291 was formerly reported to exhibit predominantly antagonistic effects at androgen receptors, a more recent study with castrated mice showed agonistic properties at skeletal muscles while prostate tissue remained unaffected. [87] ORM-11984 was assessed as to its ability to improve bone formation when implanted as sustained-release formulation in close proximity to the relevant location but did not prove useful in the employed setting. [88] Noteworthy in the context of doping controls were also reports on the anabolic properties of MT-102 (S-pindolol, espindolol), an established beta-receptor blocking agent.…”

Section: Other Anabolic Agentsmentioning

confidence: 99%

“…Besides the commonly collected specimens of urine, serum, and whole blood, a growing interest in alternative test matrices such [27][28][29]31,33,35] S1 Anabolic Agents 1 Anabolic androgenic steroids [36][37][38][39][43][44][45][46][47][48][49][50][51][52][53][54][55][56] a. exogenous [63][64][65]67,69,70] 2 Other anabolic agents - [85,86,92,93] - [60,[87][88][89][90][91][92] S2 Peptide hormones, growth factors, related substances and mimetics 1 Erythropoiesis-Stimulating Agents [119] [ 27,33,105,106,112] - [24,27,…”

Section: Introductionmentioning

confidence: 99%

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Annual banned‐substance review: analytical approaches in human sports drug testing

Thevis

Kuuranne

Walpurgis

et al. 2016

Drug Testing and Analysis

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The aim of improving anti-doping efforts is predicated on several different pillars, including, amongst others, optimized analytical methods. These commonly result from exploiting most recent developments in analytical instrumentation as well as research data on elite athletes' physiology in general, and pharmacology, metabolism, elimination, and downstream effects of prohibited substances and methods of doping, in particular. The need for frequent and adequate adaptations of sports drug testing procedures has been incessant, largely due to the uninterrupted emergence of new chemical entities but also due to the apparent use of established or even obsolete drugs for reasons other than therapeutic means, such as assumed beneficial effects on endurance, strength, and regeneration capacities. Continuing the series of annual banned-substance reviews, literature concerning human sports drug testing published between October 2014 and September 2015 is summarized and reviewed in reference to the content of the 2015 Prohibited List as issued by the World Anti-Doping Agency (WADA), with particular emphasis on analytical approaches and their contribution to enhanced doping controls.

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BA321, a novel carborane analog that binds to androgen and estrogen receptors, acts as a new selective androgen receptor modulator of bone in male mice

Watanabe

Hirata

Tominari

et al. 2016

Biochemical and Biophysical Research Communications

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Selective androgen receptor modulator activity of a steroidal antiandrogen TSAA-291 and its cofactor recruitment profile

Cited by 13 publications

References 23 publications

A selective androgen receptor modulator SARM‐2f activates androgen receptor, increases lean body mass, and suppresses blood lipid levels in cynomolgus monkeys

A selective androgen receptor modulator SARM‐2f activates androgen receptor, increases lean body mass, and suppresses blood lipid levels in cynomolgus monkeys

Annual banned‐substance review: analytical approaches in human sports drug testing

BA321, a novel carborane analog that binds to androgen and estrogen receptors, acts as a new selective androgen receptor modulator of bone in male mice

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