S-40503

Overview

S-40503 (also written S 40503 or S40503) is a nonsteroidal selective androgen receptor modulator (SARM) developed by Kaken Pharmaceutical Co., Ltd. (Japan). It is a true SARM — a small-molecule androgen receptor ligand. It is NOT a peptide (it is not an amino-acid chain) and NOT an anabolic steroid (its scaffold is nonsteroidal). It appears in this peptide reference because it is discussed alongside peptides in the fitness and "research chemical" community, not because it is one.

Everything known about S-40503 comes from preclinical rat studies — chiefly a single 2003 characterization in rat models of osteoporosis (Hanada et al., Biol Pharm Bull 2003). Its highest phase of development is preclinical; there are no known human clinical trials (no ClinicalTrials.gov records identified). Its defining feature is a bone-first anabolic profile: in castrated (orchiectomized) male rats it raised femoral bone mineral density and levator-ani muscle mass comparably to DHT (dihydrotestosterone) while, notably, not increasing prostate weight — whereas DHT increased prostate weight ~1.5-fold. In ovariectomized female rats it increased bone mineral density and the biomechanical strength of femoral cortical bone. It is often characterized as a lead/prototype compound intended to seed derivatives with better bioavailability and a longer half-life, rather than as a drug candidate in its own right.

Chemistry and structure

S-40503 is a nonsteroidal small molecule — an amino-acid chain it is not, and a steroid nucleus it is not.

Mechanism of action

• Androgen receptor (AR) agonism. In its original characterization S-40503 preferentially bound the androgen receptor with nanomolar affinity among nuclear receptors, acting as a nonsteroidal AR agonist. No numeric Ki/IC50 is reported in the accessible abstract — only "nanomolar." As a nonsteroidal small molecule it is fundamentally NOT a peptide. [In vitro] (PMID 14600402)
• Tissue-selective anabolic action — bone and muscle, sparing the prostate. In orchiectomized rats S-40503 raised femoral BMD and levator-ani muscle mass like DHT but did not increase prostate weight at any dose tested, whereas DHT increased prostate weight ~1.5-fold. The tissue-selective mechanism behind SARMs is generally attributed to differential AR conformation and cofactor recruitment, but the exact molecular basis for S-40503 is not established. [Animal] (PMID 14600402)
• Direct bone-formation (anabolic) activity. An increased periosteal mineral apposition rate in femur indicated direct bone formation, and the bone benefit persisted in immobilized/ovariectomized animals — suggesting an effect not solely secondary to increased muscle mass. [Animal] (PMID 14600402)

Research and evidence

The evidence base is entirely preclinical (rat models and in-vitro). There are no known human trials of S-40503 for any indication.

Human evidence in context. There is none. S-40503 has no known human clinical trial, so there are no completed human studies establishing efficacy for bone health, muscle growth, or any medical indication. All effect claims rest on rat studies; the binding data are in vitro. Human pharmacokinetics — half-life, oral bioavailability, and metabolism — are not established / not found in sources; secondary sources note only qualitatively that a poor in vivo half-life/bioavailability was a limitation, without numeric values. Whether any derivative program advanced beyond the 2003 rat studies is not established.

Status and regulation

• Regulatory approval: None. S-40503 is not approved by the FDA, the EMA, or any other regulator for any indication. Its highest phase of development is preclinical (rat models only) — there are no known human trials. The current status of Kaken Pharmaceutical's development program is not established and appears stalled or discontinued after the 2003 studies.
• Anti-doping: Prohibited by the World Anti-Doping Agency (WADA) at all times (in- and out-of-competition), classified under Anabolic Agents — Other Anabolic Agents (SARMs), S1.2. WADA sport-eligibility is a separate axis from legality.
• Market reality: Outside preclinical research it would be sold only as an unregulated "research chemical" of unknown identity, purity, and potency (see Safety).

Safety

Documented and expected safety signals (tagged by evidence type):

• No human safety data [Human]. No clinical safety, tolerability, or pharmacokinetic data exist for S-40503. Absence of trials means human adverse effects are unquantified, not absent. Source: Wikipedia (S-40503).
• SARM-class hepatotoxicity / drug-induced liver injury (DILI) [Human]. The FDA has warned that SARMs as a class are associated with serious or life-threatening liver injury, including acute liver failure. Class-level, not specific to S-40503. Source: FDA SARM consumer update.
• Testosterone / HPTA suppression [Hypothesis]. AR agonists in the SARM class characteristically suppress endogenous testosterone and the HPTA; the FDA also lists testicular shrinkage, infertility, and sexual dysfunction. Not directly measured for S-40503. Source: FDA SARM consumer update.
• Cardiovascular and other systemic SARM harms [Human]. The FDA links SARM-containing products to increased risk of heart attack and stroke, plus psychosis/hallucinations and sleep disturbances. Class-level, not S-40503-specific. Source: FDA SARM consumer update.
• Prostate-sparing in animals is not a human safety claim [Animal]. The prostate-sparing profile was observed in castrated rats and must not be read as evidence of human safety or of being a "safer" androgen. Source: PMID 14600402.

Legal status

How it compares

S-40503 is often grouped with other SARMs and "research chemicals." The honest framing:

• Andarine (S-4) — do not confuse the two. Despite the similar-looking code, andarine ("S-4") is a different compound. Andarine (a GTx arylpropionamide SARM) at least reached early Phase 1 before being abandoned; S-40503 has no known human trials at all and comes from a different developer (Kaken, Japan).
• Ostarine and testolone (RAD-140) — other nonsteroidal SARMs that share S-40503's mechanism (AR agonism), WADA S1.2 status, and lack of approval, but that have human clinical data S-40503 lacks.

The decisive point: S-40503 is a preclinical, unapproved research reagent with a bone-first anabolic profile shown only in rats, often framed as a lead compound for derivatives. It is not a "milder, safer, or legal alternative to steroids," and its prostate-sparing profile in rats is not a human safety claim. See the Muscle, growth & hormones overview.

Common misconceptions

• "S-40503 is a peptide." No. It is a nonsteroidal small molecule (C15H23N3O3, 293.36 g/mol). It is not a peptide and not a steroid. It is covered here only because it is discussed and stacked with peptides.
• "S-40503 is the same as S-4 (andarine)." No. They are different compounds despite the similar-looking codes; S-40503 comes from Kaken Pharmaceutical (Japan) and has no known human trials, whereas andarine was a GTx compound that reached early Phase 1.
• "It spares the prostate, so it's a safe androgen." No. The prostate-sparing profile was seen in castrated rats, not humans, and is not a human safety claim. S-40503 has essentially no human safety data, and its drug class is FDA-flagged for liver injury and testosterone suppression.
• "There's human evidence it builds bone/muscle." No. All effect data are from rat models; there are no known human trials and no human efficacy, safety, or dosing data.
• "If it's labeled S-40503, 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 as of the "updated" date above. It is not medical advice, not legal advice, a recommendation, or a guide to obtaining or using any substance. Last reviewed 2026-07-10.