In Vivo Metabolism and Final Disposition of a Novel Nonsteroidal Androgen in Rats and Dogs

@article{Perera2006InVM,
  title={In Vivo Metabolism and Final Disposition of a Novel Nonsteroidal Androgen in Rats and Dogs},
  author={Minoli A. Perera and Donghua Yin and Di Wu and Kenneth K. Chan and Duane D. Miller and James T Dalton},
  journal={Drug Metabolism and Disposition},
  year={2006},
  volume={34},
  pages={1713 - 1721}
}
  • M. Perera, D. Yin, +3 authors J. Dalton
  • Published 1 October 2006
  • Biology, Chemistry, Medicine
  • Drug Metabolism and Disposition
Compound S-4 (S-3-(4-acetylamino-phenoxy)-2-hydroxy-2-methyl-N-(4-nitro-3-trifluoromethyl-phenyl)-propionamide) is a novel nonsteroidal androgen agonist that mimics many of the beneficial pharmacologic effects of testosterone with lesser effects on the prostate. S-4 demonstrated high androgen receptor binding affinity as well as anabolic specificity during in vivo pharmacologic studies in rats, identifying it as the first member of a new class of selective androgen receptor modulators. The… 
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19 Citations

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Citation Type

Characterization of in vitro generated metabolites of the selective androgen receptor modulators S-22 and S-23 and in vivo comparison to post-administration canine urine specimens.
TLDR
The structure of analytically useful urinary metabolites should be elucidated to provide targets for sensitive and retrospective analysis and M3 was chemically synthesized, characterized by nuclear magnetic resonance spectroscopy and high resolution/high accuracy mass spectrometry, and chosen as primary target for future doping control analyses.
Effect of para halogen modification of S-3-(phenoxy)-2-hydroxy-2-methyl-N-(4-nitro-3-trifluoromethyl-phenyl)-propionamides on metabolism and clearance
TLDR
It is suggested that as lipophilicity increased the free fraction was reduced thus compensating for metabolic liability and resulting in the apparent discrepancy between CLint and CL total of halogen-substituted SARMs series.
Absorption, distribution, metabolism and excretion of the novel SARM GTx-024 [(S)-N-(4-cyano-3-(trifluoromethyl)phenyl)-3-(4-cyanophenoxy)-2-hydroxy-2-methylpropanamide] in rats
TLDR
In the rat GTx-024 is completely absorbed, widely distributed, biotransformed through several metabolic pathways, and eliminated in feces primarily as an unchanged drug.
Pharmacokinetics, biodistribution and metabolism of a novel selective androgen receptor modulator designed for prostate cancer imaging.
TLDR
The extensive plasma clearance and de-iodination of S-26 likely contribute to its lack of AR tissue selectivity in vivo, and future studies using metabolically stable ligands with less lipophilicity and higher AR binding affinity may represent a promising and rational approach for AR-mediated imaging.
Detection of the arylpropionamide-derived selective androgen receptor modulator (SARM) S-4 (Andarine) in a black-market product.
TLDR
That SARMs are the subject of misuse even without clinical approval was proved for the first time by the detection of the drug candidate Andarine, advertised, sold and supplied via the Internet.
Synthetic anabolic agents: steroids and nonsteroidal selective androgen receptor modulators.
TLDR
Nonsteroidal alternatives to AAS have been developed that selectively activate the androgen receptor in either muscle tissue or bones, and these compounds possess a high potential for misuse in sports and will be the subject of future doping control assays.
Mass spectrometric characterization of urinary metabolites of the selective androgen receptor modulator andarine (S-4) for routine doping control purposes.
TLDR
In the present communication, the mass spectrometric characterization of urinary metabolites of the SARM Andarine compared with earlier in vitro and animal studies is reported and will support future efforts to effectively screen for and confirm the misuse of the non-approved drug candidate Andarine.
Selective androgen receptor modulators: comparative excretion study of bicalutamide in bovine urine and faeces.
TLDR
Bicalutamide, a non-steroidal SARM used in human treatment of non-metastatic prostate cancer because of its anti-androgenic activity exhibiting no anti-anabolic effects, was compared and mainly excreted under its free form in a calf, and phase I and II metabolites were investigated.
Recent advances in the development of selective androgen receptor modulators
TLDR
A new class of molecules targeting androgen receptors called selective androgen receptor modulators is being developed, analogous to the clinically successful and at present marketed selective estrogen receptors modulators.
Nonsteroidal selective androgen receptor modulators (SARMs): dissociating the anabolic and androgenic activities of the androgen receptor for therapeutic benefit.
TLDR
This Award Address attempts to chronicle the landmark discoveries, organize the SARM landscape into clinically relevant bins, and provide insight into the clinical prospects for SARMs.
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