For laboratory research use only. Not for human consumption. All compounds referenced in this article are sold by Explicit SARMs solely as reference materials for in-vitro and animal research by qualified professionals. Nothing here is medical advice, and no statement has been evaluated by the FDA. These materials are not intended to diagnose, treat, cure or prevent any disease.
S4, also known as Andarine and GTx-007, is one of the earliest nonsteroidal selective androgen receptor modulators (SARMs) to be characterized in detail. It came out of the same aryl-propionamide program that later produced Ostarine (MK-2866), and much of what is understood about how tissue selectivity is measured in rats was established in S4 studies.
S4 never progressed through large clinical trials, so its literature is primarily preclinical: rat studies of muscle, bone, the pituitary and pharmacokinetics. This review summarizes that record and the practical points that matter for laboratory work. Explicit SARMs supplies S4 Andarine Capsules strictly as laboratory reference material.
What Is S4?
S4 is S-3-(4-acetylamino-phenoxy)-2-hydroxy-2-methyl-N-(4-nitro-3-trifluoromethyl-phenyl)-propionamide. [3]
- Common names: S4, S-4, Andarine, GTx-007
- Class: nonsteroidal selective androgen receptor modulator (aryl-propionamide)
- Primary target: androgen receptor
- Origin: the Dalton and Miller research groups, developed with GTx, Inc.
- Research setting: primarily rat and dog studies
- Regulatory status: not approved by the FDA or any other regulator for any indication
Mechanism of Action
S4 binds the androgen receptor’s ligand-binding domain and activates it. Its structure derives from the nonsteroidal antiandrogen scaffold of hydroxyflutamide and bicalutamide, modified so that the molecule acts as an agonist rather than an antagonist. [5]
The tissue selectivity reported for S4 in rats follows the general SARM model. S4 is not a substrate for 5-alpha reductase, so it does not undergo the amplification that testosterone undergoes in the prostate when converted to DHT, and it is not aromatized to estrogen. Its effects on the prostate and seminal vesicles were therefore much smaller than those of DHT at exposures that produced comparable effects in muscle. [1]
S4 also showed agonist activity in the pituitary, lowering LH and FSH in castrated rats in a dose-dependent manner. [1] That pituitary activity is a reminder that SARMs are not inert in the reproductive axis.
Research History
S4 was developed in the early 2000s. A 2004 Xenobiotica paper reported its pharmacokinetics in rats [3], a 2006 study described its metabolism and disposition in rats and dogs [4], and two key efficacy papers followed: a 2005 orchidectomized rat study [1] and a 2007 ovariectomized rat study. [2]
GTx ultimately prioritized Ostarine for clinical development, and Ostarine, rather than S4, went on to phase 2 and phase 3 trials.
What Published Studies Report
Pharmacokinetics
In rats, S4 was rapidly absorbed and slowly cleared, with a moderate volume of distribution. Bioavailability by gavage was dose dependent, being complete at lower doses, and the half-life ranged from about 2.6 to 5.3 hours across the doses tested. [3] A separate study characterized its in-vivo metabolism and elimination in rats and dogs. [4]
Orchidectomized rats
Gao and colleagues treated castrated male rats with S4, DHT or vehicle for eight weeks, beginning twelve weeks after castration. S4 restored soleus muscle mass and strength and levator ani mass to levels seen in intact animals. DHT stimulated the prostate and seminal vesicles to more than twice intact-control weights, while S4 returned those organs to only about 16 to 17% of control levels. S4 also produced a larger increase in total body bone mineral density than DHT and reduced LH and FSH. [1]
Ovariectomized rats
Kearbey and colleagues studied S4 in an ovariectomy model of accelerated bone loss in female rats over 120 days. They reported that S4 maintained whole-body and trabecular bone mineral density and cortical content, increased bone strength in biomechanical testing, and decreased body fat. [2]
Research Considerations
- Classic selectivity assay. S4 is a well-documented reference compound for levator ani versus prostate and seminal vesicle comparisons in castrated rats. [1]
- Pituitary effects. Include LH and FSH measurements, because S4 suppresses gonadotropins in rats. [1]
- Short half-life in rats. With a reported half-life of a few hours in rats, sampling schedules for pharmacokinetic work need to be dense. [3]
- Bone models. The ovariectomized rat model offers a direct comparison with published S4 data using DXA, pQCT and biomechanical testing. [2]
- Reference standards. Validate analytical methods against an authenticated S4 standard, and confirm identity and purity before each study.
Why S4 Matters to SARM Research
Even without a clinical program, S4 is historically important. Several concepts now taken for granted in SARM research were demonstrated clearly in S4 studies:
- Dissociation of anabolic and androgenic effects. The 2005 orchidectomized rat study showed restoration of muscle measures with much smaller effects on the prostate and seminal vesicles than DHT, which became the template for later selectivity claims. [1]
- Bone activity independent of aromatization. Because S4 is not aromatized to estrogen, its effects on bone in rats pointed to direct androgen receptor-mediated activity in bone. [1][2]
- Pharmacokinetic suitability of the scaffold. The rat pharmacokinetic work showed that the aryl-propionamide template could be bioavailable without injection, which supported development of later compounds such as Ostarine. [3]
For laboratories, this makes S4 a well-documented reference compound for validating rat selectivity assays and for comparing newer aryl-propionamide SARMs against an established profile.
WADA Status
Andarine is named explicitly in WADA section S1.2 (Other Anabolic Agents) and is prohibited at all times. [7] Anti-doping laboratories have published detection methods for aryl-propionamide SARMs and their metabolites. [6]
Storage, Purity and COA
- Store capsules sealed, dry and away from light and heat.
- Log lot numbers and receipt dates with study records.
- Review the lot-specific Certificate of Analysis. It should report HPLC purity, confirm identity by mass spectrometry, and list the lot number and analysis date.
- S4 is a single enantiomer, so chiral purity can be relevant. Ask whether chiral analysis is available for a given lot.
For lot documentation, use the contact page.
Related Research Compounds
- Ostarine MK-2866 Capsules, the clinically developed successor in the same chemical family
- S23 Capsules, a later, higher-affinity aryl-propionamide SARM (see the S-23 research overview)
- MK-2866 Liquid, Ostarine in solution form
- Class overview: SARMs vs Traditional Research Compounds and the SARMs collection
Frequently Asked Questions
Are S4 and Andarine the same compound?
Yes. S4 (or S-4) is the research code, GTx-007 was a development code, and Andarine is the nonproprietary-style name.
How is S4 related to Ostarine?
Both are aryl-propionamide SARMs from the same research program. Ostarine was the compound selected for clinical development.
Has S4 been tested in large human trials?
No. Its published record is mainly rat and dog studies of pharmacokinetics, metabolism, muscle and bone.
What did the rat studies find?
In castrated rats, S4 restored muscle measures with much smaller effects on the prostate than DHT, and in ovariectomized rats it maintained bone mineral density and bone strength. [1][2]
Is S4 approved by the FDA?
No. S4 has never been approved by the FDA or any other regulator.
Is S4 prohibited in sport?
Yes. Andarine is named in WADA section S1.2 and is prohibited at all times. [7]
Why did S4 not progress to large clinical trials?
The sponsor prioritized Ostarine, a closely related compound from the same program, for clinical development. Published sources do not provide a complete account of every factor behind that decision.
Which animal models are best documented for S4?
The orchidectomized male rat and the ovariectomized female rat are the best documented, with published data on muscle, bone, reproductive tissues and gonadotropins. [1][2]
Has S4 metabolism been characterized?
Yes. Its metabolism and disposition were studied in rats and dogs, which supports analytical method development and interpretation of exposure data. [4]
References
- Gao W, et al. Selective androgen receptor modulator treatment improves muscle strength and body composition and prevents bone loss in orchidectomized rats. Endocrinology. 2005. PubMed 16099859
- Kearbey JD, et al. Selective Androgen Receptor Modulator (SARM) treatment prevents bone loss and reduces body fat in ovariectomized rats. Pharm Res. 2007. PubMed 17063395
- Kearbey JD, et al. Pharmacokinetics of S-3-(4-acetylamino-phenoxy)-2-hydroxy-2-methyl-N-(4-nitro-3-trifluoromethyl-phenyl)-propionamide in rats, a non-steroidal selective androgen receptor modulator. Xenobiotica. 2004. PubMed 15204699
- Perera MA, et al. In vivo metabolism and final disposition of a novel nonsteroidal androgen in rats and dogs. Drug Metab Dispos. 2006. PubMed 16815963
- Narayanan R, et al. Development of selective androgen receptor modulators (SARMs). Mol Cell Endocrinol. 2018. PubMed 28624515
- Thevis M, Schanzer W. Detection of SARMs in doping control analysis. Mol Cell Endocrinol. 2018. PubMed 28137616
- World Anti-Doping Agency. 2026 Prohibited List. wada-ama.org
For laboratory research use only. Not for human consumption. All compounds referenced in this article are sold by Explicit SARMs solely as reference materials for in-vitro and animal research by qualified professionals. Nothing here is medical advice, and no statement has been evaluated by the FDA. These materials are not intended to diagnose, treat, cure or prevent any disease.