S-1

Overview

S-1 (also GTx S-1) is an early nonsteroidal selective androgen receptor modulator (SARM) of the arylpropionamide class. Chemically it is a small molecule — it is a true nonsteroidal SARM, NOT a peptide and NOT a steroid. It appears in this peptide reference because SARMs are frequently discussed and stacked alongside peptides in the fitness and "research chemical" community, not because S-1 is one.

S-1 was developed by James T. Dalton, Duane D. Miller and colleagues at the University of Tennessee / GTx, Inc. It is a close structural analog of andarine (S-4): the two come from the same arylpropionamide patent series (adjacent CAS registry numbers — S-1 is 401900-41-2, andarine is 401900-40-1), and S-1 differs mainly at the phenoxy B-ring substituent (a 4-fluorophenoxy ether in S-1 versus andarine's acetamido/nitro-phenoxy group). In the foundational pharmacology paper (Yin et al., 2003), S-1 was one of several arylpropionamide leads characterized in vitro and in castrated rats.

S-1 is purely preclinical. It was an early lead in the program that ultimately advanced enobosarm (ostarine) into clinical development — not S-1 itself. No human clinical trial for S-1 was identified, and there are no human safety or efficacy data.

Chemistry and structure

S-1 is a nonsteroidal arylpropionamide small molecule, not an amino-acid chain and not a steroid nucleus. Its IUPAC name is (2S)-3-(4-fluorophenoxy)-2-hydroxy-2-methyl-N-[4- nitro-3-(trifluoromethyl)phenyl]propanamide.

Mechanism of action

• Androgen receptor (AR) ligand. S-1 binds the androgen receptor as a nonsteroidal arylpropionamide ligand. In the lead series characterized by Yin et al. 2003, the arylpropionamide compounds (including S-1 and S-4/andarine) showed moderate-to-high AR binding affinity, with reported Ki values across the series in roughly the 4–37 nM range. Arylpropionamide SARMs are structural derivatives of the AR antagonist bicalutamide, re-engineered toward agonist activity. [In vitro]
• Tissue-selective anabolic agonist. In castrated rats, S-1 stimulated the levator ani (anabolic) muscle to a greater relative degree than the androgenic organs (prostate, seminal vesicles) — the defining SARM tissue-selectivity profile. Its anabolic activity was similar to or greater than testosterone propionate while its androgenic potency/efficacy was lower. This selectivity is thought to arise from tissue-specific AR conformation / coregulator recruitment rather than 5-alpha-reductase amplification. [Animal]
• Andarine (S-4) analog. S-1 differs from andarine principally at the phenoxy B-ring substituent (a fluorine / 4-fluorophenoxy group in S-1 versus andarine's acetamido-nitro group). Their adjacent CAS numbers (S-1 401900-41-2; andarine 401900-40-1) place them in the same arylpropionamide patent series. [In vitro]
• No significant LH/FSH suppression near effective doses in rats. Neither S-1 nor S-4 caused significant luteinizing hormone (LH) or follicle-stimulating hormone (FSH) suppression at doses near the ED50 in the rat model. This is an animal finding only — it does NOT establish that S-1 spares the human hypothalamic-pituitary-testicular (HPTA) axis, and the SARM class broadly is associated with testosterone/HPTA suppression in humans. [Animal]

Research and evidence

Human evidence in context. There is none. S-1 was never taken into human trials; it was an early preclinical lead in a program that clinically advanced a different compound (enobosarm/ostarine). All positive findings for S-1 come from in vitro binding work and castrated-rat pharmacology. Human pharmacokinetics (bioavailability, half-life) and even detailed rat PK for S-1 specifically were not found in these sources, and the single S-1 AR-binding Ki was not isolated from the reported series range in the reviewed sources.

Status and regulation

• Regulatory approval: None. S-1 is not approved by the FDA, the EMA, or any other regulator for any indication. It is a preclinical research reagent that never entered human development.
• Anti-doping: Prohibited by the World Anti-Doping Agency (WADA) at all times (in- and out-of-competition) as a SARM under Anabolic Agents — Other Anabolic Agents (S1.2) (per USADA's summary of the Prohibited List). WADA sport-eligibility is a separate axis from legality.
• Identity caution: The anticancer combination drug "S-1" (tegafur / gimeracil / oteracil, PubChem CID 146157327) shares this compound's name but is an entirely different chemical entity. Do not conflate the two.

Safety

The overall picture: S-1 has no human data of any kind, sits within a drug class the FDA has flagged for liver injury and other serious harms, and — as an unregulated research chemical — carries the additional, separate hazards of contamination and mislabeling.

Legal status

How it compares

S-1 is best understood next to its own analog and its successor in the same program:

• Andarine (S-4) — S-1's close structural analog from the same arylpropionamide patent series (adjacent CAS numbers). Andarine progressed further — into an early, abandoned Phase 1 program halted over a visual side effect — whereas S-1 remained a preclinical lead.
• Ostarine (enobosarm) — the compound the arylpropionamide program actually advanced into human trials, in place of S-1. It is the far better-characterized clinical candidate; S-1 never reached that stage.

The honest framing: S-1 is an early, purely preclinical research reagent with no human data, and it belongs to a drug class the FDA has flagged for liver injury and testosterone suppression — it is not a "milder, safer, or legal alternative to steroids." See the muscle growth & hormone overview.

Common misconceptions

• "S-1 is a peptide." No. It is a nonsteroidal arylpropionamide small molecule (C17H14F4N2O5, 402.30 g/mol). It is covered here only because SARMs are discussed and stacked with peptides.
• "S-1 is a steroid." No. It is a true nonsteroidal SARM — it does not have a steroid nucleus.
• "S-1 is a proven or clinically used SARM." No. It was an early preclinical lead that never entered human trials; the program advanced ostarine (enobosarm) instead. All S-1 findings are in vitro or rat.
• "S-1 doesn't suppress your hormones — the rat data prove it's safe." No. The LH/FSH result is a rat finding near the ED50 only; it does not transfer to humans, and the SARM class does suppress the HPTA axis in people. There are no human data for S-1.
• "S-1 is the same as the cancer drug S-1." No. This SARM (PubChem CID 5288215) is a completely different chemical from the anticancer combination tegafur/gimeracil/ oteracil (CID 146157327), which merely shares the name.
• "If it's labeled S-1, that's what's in it." Not reliably. In the JAMA 2017 analysis, only about half of products sold as SARMs contained the labeled compound; many contained a different drug or nothing active.

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This entry is educational and summarizes published research and public regulatory information. It is not medical advice, a recommendation, or a guide to obtaining or using any substance. Not legal advice — check your own jurisdiction. Last reviewed 2026-07-10.