Andarine (S-4)

Technical data

INN name

Andarine

Development code

S-4

Identity and composition

Andarine (S-4) is a non-steroidal selective androgen receptor modulator (SARM), derived from arylpropionamide, studied in preclinical models for its anabolic activity on muscle and bone with less stimulation of androgenic tissues. It is offered in a presentation of 25 mg × 100 tablets. Product for research use.

Reference chemical identity data:

• CAS number: 401900-40-1
• Molecular formula: C19H18F3N3O6
• Molecular weight: 441.36 g/mol
• Synonyms: Andarine, S-4, GTx-007, Acetamidoxolutamide, Androxolutamide

Andarine is not a drug approved by regulators for clinical use. Its characterization comes mainly from preclinical literature.

Mechanism of action

Andarine (S-4) binds to the androgen receptor (AR) and acts as tissue-selective agonist: in the general SARM mechanism, the compound displaces the AR from heat-shock proteins, promotes its translocation to the nucleus and its binding to the androgen response elements (ARE). Subtle conformational changes of the AR alter the recruitment of coactivators and corepressors depending on the tissue, which in animal models is associated with a more selective anabolic activity than that of steroids.

In muscle and bone tissue it behaves as anabolic agonist, whereas in androgenic tissues (prostate, seminal vesicles) it acts as weak partial agonist. In models of orchidectomized rats, S-4 restored muscle mass and strength and prevented bone loss, with minimal prostatic stimulation —on the order of 16-17% relative to the control—, which illustrates its tissue selectivity relative to dihydrotestosterone (DHT) (PMC2039881).

Pharmacokinetics

No pharmacokinetic parameters (such as half-life or bioavailability) were confirmed in the reviewed sources for this compound. The available preclinical studies focused on outcomes pharmacodynamic following chronic treatment in animals, not in kinetic characterization. Therefore, any quantitative description of absorption, distribution, or elimination would fall outside the confirmed evidence and is deliberately omitted.

Scientific evidence

The published evidence on Andarine (S-4) is mostly preclinical and should be interpreted with caution. In rodent models —ovariectomized and orchidectomized rats— its effect on body composition, bone and muscle has been investigated. In preclinical studies it was observed that S-4 maintained bone mineral density and bone strength and reduced body fat in ovariectomized rats (PMID 17063395), and that it restored muscle mass and strength and prevented bone loss with minimal prostatic stimulation in orchidectomized rats (PMC2039881).

No approved advanced-phase clinical trial program was identified; characterization in humans is limited. Recent preclinical research additionally explores oncological uses of an exploratory nature. The preliminary evidence does not allow results to be extrapolated to people.

Research applications

Product for research use.

Aimed at:

• In vitro and animal model studies on the biology of the androgen receptor and the tissue selectivity of SARMs.
• Preclinical research in body composition, bone and muscle metabolism.
• Analytical and reference work, including the context of anti-doping control (S-4 is a known analyte).

Not applicable for:

• clinical use, therapeutic use, diagnostic or preventive.
• Use in sport: SARMs are prohibited by anti-doping agencies.
• Any clinical application: S-4 is not a drug approved by regulators.

Research protocols

The reported doses correspond to animal models and are not extrapolable to humans nor do they constitute a usage guideline. In preclinical studies in castrated rats, anabolic doses of S-4 of 3 mg/kg were associated with the recovery of muscle mass and strength (soleus muscle), restoring the prostate and seminal vesicles to only 16-17% of control levels, which demonstrates tissue selectivity relative to DHT (PMC2039881).

There are no validated dosing protocols for clinical use. For experimental work, dosing must be defined by the researcher according to their study design and model, under the applicable biosafety standards.

Reconstitution

The presentation of Andarine (S-4) of this product is in tablets (25 mg), so it does not require reconstitution with bacteriostatic water like injectable lyophilizates.

As a general laboratory reference: when a lyophilized powder compound does need to be reconstituted, one typically uses bacteriostatic water (water with ~0.9% benzyl alcohol as preservative), adding it slowly down the wall of the vial onto the solid, without shaking abruptly, and letting it dissolve by gentle rotation. This point does not apply to the tablet form.

Stability and storage

General laboratory handling guide:

• Solid form (tablets / powder): store in its original, tightly closed container, protected from light, moisture, and heat. For prolonged storage a cool, dry environment is usually preferred; refrigeration or freezing prolongs the stability of many compounds in solid form.
• Reconstituted solutions (when applicable): keep refrigerated, protected from light, and use them within a short period, since in solution the stability is lower than in solid form.

These are standard storage practices; they do not replace batch-specific stability data.

Safety profile

The safety data of Andarine (S-4) in humans are limited; the described profile comes from animal models and should be interpreted with caution.

• S-4 is not an approved compound by regulators for clinical use.
• It is banned in sport for belonging to the SARM class.
• It has been detected as adulterant in black market products and supplements, which raises quality and labeling risks (PMID 20355219).

Owing to its nature as a research material, it must be handled with appropriate protective equipment and under the laboratory's biosafety standards. No established clinical contraindications are available because of the lack of characterization in humans.

Comparative context

Compared with the dihydrotestosterone (DHT), the reference steroidal androgen in preclinical studies, Andarine (S-4) showed a profile of partial/tissue-selective agonist:

• Greater increase in total body bone mineral density than DHT in the models evaluated.
• Markedly lower prostatic stimulation at equivalent anabolic doses, consistent with its tissue selectivity.
• Unlike DHT, in some models S-4 did not induce the same fat loss.

This contrast illustrates the central characteristic of the SARM class: to seek anabolic activity on muscle and bone dissociated from the strong androgenic action of steroids. The comparisons come from animal models and do not predict responses in humans.

History and development

Andarine was developed by GTx Inc. as a therapeutic candidate targeting muscle atrophy and wasting, osteoporosis, and benign prostatic hyperplasia. Its development was supported by rodent models (ovariectomized and orchidectomized rats), in which the prevention of bone loss, the maintenance of bone mineral density, the improvement of muscle strength, and the reduction of body fat were investigated.

No approved advanced-phase clinical trial program was identified. Over time, S-4 came to appear in the literature mostly as a substance detected in black-market products and as analyte in anti-doping control (PMID 20355219), rather than as a drug in active development.

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Scientific references (5)

Peer-reviewed literature on Andarine (S-4), with its PubMed identifier where available:

• In vitro anti-carcinogenic effect of andarine as a selective androgen receptor modulator on MIA-PaCa-2 cells by decreased proliferation and cell-cycle arrest at G0/G1 phase (Bölük A et al. · Biochemical and biophysical research communications · 2023) PMID 37302286.
• Detection of the arylpropionamide-derived selective androgen receptor modulator (SARM) S-4 (Andarine) in a black-market product. (Thevis M, et al. · Drug Test Anal · 2009) PMID 20355219.
• Mass spectrometric characterization of urinary metabolites of the selective androgen receptor modulator andarine (S-4) for routine doping control purposes. (Thevis M, et al. · Rapid Commun Mass Spectrom · 2010) PMID 20623476.
• Selective Androgen Receptor Modulator (SARM) treatment prevents bone loss and reduces body fat in ovariectomized rats (Kearbey, et al. · Pharmaceutical Research · 2007) PMID 17063395.
• Exploring the potentials of S4, a selective androgen receptor modulator, in glioblastoma multiforme therapy (Yavuz, et al. · Toxicology and Applied Pharmacology · 2024) PMID 38997069.

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