Andarine

Andarine (S-4) is a selective inhibitor of AR with Ki50 value of 4 nM [1].

Androgen receptor (AR), also known as nuclear receptor subfamily 3, group C, member 4, is a type of nuclear receptor and plays an important role in DNA-binding transcription factor that regulates gene expression [2].

Andarine is a potent AR inhibitor and has a higher affinity with the reported AR inhibitor S-1, S-2 and S-3. Using a cotransfection system, it was shown that Andarine stimulated AR-mediated transcription as high as 93% at the concentration of 10 nM. [1].

In male Sprague-Dawley rat model, administration of Andarine resulted in the growth in prostate, seminal vesicles, and levator ani muscle at a dose-dependent manner and promoted their weight being maximally to 33.8, 28.2 and 101% of intact controls, respectively. Further, it was revealed that the ED50 value of Andarine functioning on prostate, seminal vesicles, and levator ani muscle was 0.43±0.01, 0.55±0.02, and 0.14±0.01 mg/day [1].

References:
[1].  Yin, D., et al., Pharmacodynamics of selective androgen receptor modulators. J Pharmacol Exp Ther, 2003. 304(3): p. 1334-40.
[2].  Thevis, M., et al., Mass spectrometric characterization of urinary metabolites of the selective androgen receptor modulator S-22 to identify potential targets for routine doping controls. Rapid Commun Mass Spectrom, 2011. 25(15): p. 2187-95.

Detection of the arylpropionamide-derived selective androgen receptor modulator (SARM) S-4 (Andarine) in a black-market product.[Pubmed:20355219]

Drug Test Anal. 2009 Aug;1(8):387-92.

Non-steroidal and tissue-selective anabolic agents such as selective androgen receptor modulators (SARMs) represent a promising class of therapeutics for the treatment of various diseases such as sarcopenia or cancer cachexia. Advanced compounds of SARMs are based on an arylpropionamide-derived structure and leading drug candidates have successfully completed phase-II-clinical trials. Although none of these therapeutics have been approved, their performance-enhancing qualities and the black-market availability of these products makes them a viable target for misuse in the athletic community. In 2008, SARMs were added to the Prohibited List established by the World Anti-Doping Agency (WADA). 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 (also referred to as S-4, S-3-(4-acetylamino-phenoxy)-2-hydroxy-2-methyl-N-(4-nitro-3-trifluoromethyl-pheny l)-propionamide), advertised, sold and supplied via the Internet. The oily liquids, declared as green tea extracts and face moisturizer, were assayed using state-of-the-art analytical procedures and S-4 was found at concentrations of approximately 150 mg/mL. The authenticity of the product was demonstrated in comparison to reference material by liquid chromatography, high resolution/high accuracy (tandem) mass spectrometry using positive and negative electrospray ionization, and comparison to reference material. Moreover, an impurity resulting from poor product purification was detected, accounting for approximately 10% of S-4. This consisted of 2-hydroxy-2-methyl-N-(4-nitro-3-trifluoromethyl-phenyl)-3-(4-nitro-3-trifluoromet hyl-phenylamino)-propionamide. The ease of purchasing non-approved drug candidates that could potentially increase athletic performance demonstrates the need to operate proactively in the continued fight against doping. The early inclusion of emerging drugs into routine sports drug testing procedures is a key element of preventive doping research, limiting the options for cheating athletes who aim to undermine the doping control system.

Mass spectrometric characterization of urinary metabolites of the selective androgen receptor modulator andarine (S-4) for routine doping control purposes.[Pubmed:20623476]

Rapid Commun Mass Spectrom. 2010 Aug 15;24(15):2245-54.

Selective androgen receptor modulators (SARMs) are potent anabolic agents with tissue-selective properties. Due to their potential misuse in elite sport, the World Anti-Doping Agency (WADA) has prohibited SARMs since 2008, and although no representative drug candidate has yet received full clinical approval, recent findings of SARMs illegally sold via the internet have further supported the need to efficiently test for these compounds in doping controls. In the present communication, the mass spectrometric characterization of urinary metabolites of the SARM Andarine (also referred to as S-4) compared with earlier in vitro and animal studies is reported. Liquid chromatography interfaced to high-resolution/high-accuracy (tandem) mass spectrometry was used to identify phase I and II metabolites, confirming the predicted target analytes for sports drug testing purposes including the glucuronic acid conjugates of the active drug, its monohydroxylated and/or deacetylated product, the hydrolysis product resulting from the removal of the compound's B-ring, as well as the sulfate of the monohydroxylated and the deacetylated phase I metabolite. The obtained data will support future efforts to effectively screen for and confirm the misuse of the non-approved drug candidate Andarine.