B tier · viable
The only compound in this group with completed randomised phase 3 human trials, but both POWER trials missed their FDA-agreed co-primary responder endpoints and the drug remains unapproved anywhere.
ostarine
Enobosarm is the most extensively studied non-steroidal SARM, with randomised placebo-controlled phase 2 and phase 3 data in cancer-associated muscle wasting and phase 2 data in AR-positive breast cancer. It has consistently increased lean body mass relative to placebo, but has repeatedly failed to demonstrate corresponding improvement in physical function, and no regulator has approved it for any indication.
// we supply this one
available as a research reagent
≥ 98% HPLC · research solution · batch certificate published. Grade B above is our own and is not adjusted because we stock it.
the explanation
This is the one compound here that actually made it into large human trials, and it did reliably add lean mass compared with placebo. The problem is that the extra mass did not translate into people being measurably stronger or more functional, which is why it was never approved.
regulatory status
Not approved by FDA or any regulator; WADA-prohibited; not a lawful dietary supplement ingredient
Enobosarm has never been approved for any indication in any jurisdiction despite completing phase 3 trials. FDA classifies SARMs sold in bodybuilding products as unapproved drugs and has issued repeated public safety notifications (2017, with the fraudulent-products page maintained through 2025) citing heart attack, stroke, psychosis, liver injury and acute liver failure, infertility and testicular shrinkage. All SARMs including enobosarm are prohibited at all times under WADA class S1.2 (Other Anabolic Agents). The SARMs Control Act was introduced in the US Senate in 2018 (S.2742) and reintroduced in 2019 (S.2895) to place SARMs in Schedule III of the Controlled Substances Act; per USADA, no further action had been taken on the bill as of 2022, so SARMs remain outside the CSA schedules while still being illegal to market as supplements or drugs.
how it works · proposed mechanism
Enobosarm is a non-steroidal selective androgen receptor modulator that binds the androgen receptor and recruits coregulators in a tissue-dependent manner.
Androgen receptor ligand binding
Enobosarm binds the AR ligand-binding domain as a non-steroidal aryl-propionamide, without the steroid nucleus that permits aromatisation to oestrogens or 5-alpha reduction to DHT. This altered scaffold produces a different receptor conformation from testosterone.
Tissue-selective coregulator recruitment
The receptor conformation induced by enobosarm recruits a coactivator profile that favours anabolic gene programmes in skeletal muscle and bone over androgenic programmes in prostate and skin. This differential recruitment is the proposed basis for the observed muscle-versus-prostate selectivity in preclinical models.
Hypothalamic-pituitary feedback
As an AR agonist, enobosarm exerts negative feedback on the hypothalamic-pituitary-gonadal axis, producing dose-dependent suppression of endogenous testosterone, LH, FSH and SHBG. This is a class effect documented across SARM human trials rather than a compound-specific finding.
what’s reported
evidence shape
11 sourcesThe composition of the cited literature by study type. This describes the shape of the evidence, not its quality — and it does not by itself set the grade.
⚠ the catch
Enobosarm is the strongest evidence base in this group and it still failed its registrational endpoints, which is the clearest available demonstration that lean mass gain on a DXA scan does not automatically produce functional benefit. Its comparatively good trial record is routinely cited in marketing as though it were a safety clearance, when in fact it is a record of a drug that was studied properly and did not meet the bar.
key published findings
- Human trial (phase 3, POWER1 and POWER2, 2013): two identically designed randomised double-blind placebo-controlled trials, each n=300 NSCLC patients receiving 3 mg once daily or placebo for 147 days; both trials failed the FDA-agreed co-primary responder endpoints, with LBM responder p=0.036 (POWER1) and p=0.113 (POWER2) and stair climb power responder p=0.315 and p=0.289 respectively.
- Human trial (phase 3, continuous analysis): analysed as a continuous variable rather than a responder rate, enobosarm produced a consistent lean body mass effect versus placebo at day 84 in both trials (p=0.0003 and p=0.0227), with reported gains in the 0.41–0.47 kg range.
- Human trial (phase 2, Dobs et al., Lancet Oncology, 2013): randomised double-blind placebo-controlled trial of enobosarm in patients with cancer showed significant increases in lean body mass versus placebo but did not establish improvement in muscle strength.
- Human trial (phase 2, elderly, 2011): a double-blind placebo-controlled trial in elderly men and postmenopausal women reported statistically significant improvements in total lean body mass and physical function without adverse effects on hair growth or sebum production.
- Human trial (phase 2, oncology, Lancet Oncology, 2024, Study G200802): a randomised open-label multicentre parallel-design phase 2 trial evaluated enobosarm in AR-positive, ER-positive, HER2-negative advanced breast cancer; enobosarm has since entered phase 3 evaluation at 9 mg/day in this indication, which remains its only active registrational pathway.
limitations of the evidence
- The phase 3 program was conducted in NSCLC patients on first-line chemotherapy, so results do not generalise to healthy individuals, and no phase 3 trial has ever been run in a healthy or athletic population.
- The repeated dissociation between lean mass gain and functional improvement remains unexplained and is the central unresolved question in the enobosarm literature.
- Long-term safety beyond the 147-day POWER exposure window is uncharacterised, and trial safety data cannot be extrapolated to the unregulated, frequently mislabelled products sold under the ostarine name.
documented safety signals
- Drug-induced liver injury: NIH LiverTox assigns SARMs as a class a likelihood score of B (likely cause of clinically apparent liver injury), and a published case report specifically attributes DILI to enobosarm (Weinblatt et al., Journal of Medical Cases).
- The characteristic SARM hepatotoxicity phenotype is cholestatic jaundice with a distinctive dissociated profile: bilirubin initially 4.0–8.0 mg/dL and often peaking above 30 mg/dL, with ALT only 2–5 times ULN and near-normal alkaline phosphatase; ALT paradoxically falls while bilirubin rises. Latency is typically 2–3 months, ranging from weeks to a year.
- Liver biopsy in these cases shows moderate-to-severe canalicular ('bland') cholestasis with minimal inflammation. LiverTox reports cases were invariably self-limited with resolution in 1–6 months after discontinuation and no deaths or transplants, but severe hyperbilirubinaemia occasionally caused reversible renal dysfunction requiring temporary dialysis.
- Dose-dependent suppression of endogenous testosterone, free testosterone, LH, FSH and SHBG is a consistent class finding in SARM human trials, with uncharacterised recovery kinetics after prolonged exposure.
- HDL cholesterol suppression is documented across SARM phase 1 data, a recognised adverse cardiovascular risk marker.
- FDA's public safety notification on bodybuilding products containing SARMs names increased risk of heart attack and stroke, psychosis and hallucinations, sleep disturbance, sexual dysfunction, liver injury and acute liver failure, infertility, miscarriage in pregnancy and testicular shrinkage, and notes life-threatening reactions including liver injuries requiring hospitalisation.
- Products sold as ostarine are unregulated and have been repeatedly found in anti-doping and regulatory testing to be mislabelled, underdosed, overdosed or to contain entirely different undeclared compounds, meaning clinical-trial safety data do not describe what is actually in consumer products.
- Ostarine is among the most frequently detected substances in adverse analytical findings in sport, including from claimed supplement contamination.
identity
| full name | Enobosarm (ostarine, MK-2866, GTx-024, S-22) |
| category | Anabolic & Receptor |
| modality | small molecule |
| formula | C19H14F3N3O3 |
| molar mass | 389.3 g/mol |
| cas | 841205-47-8 |
| half-life | ~22 hours (mean terminal half-life reported ~22.0 ± 5.8 h in human volunteers) |
laboratory handling
| storage | Reference material: store as a solid, desiccated and protected from light, at -20 °C for long-term stability; solutions in organic solvent are typically stored at -80 °C and freeze-thaw cycles minimised. |
| solubility | Lipophilic small molecule; soluble in DMSO, ethanol and DMF, poorly soluble in aqueous buffer. Vendor certificate-of-analysis solubility figures vary and should be taken from the specific lot. |
| co-studied with | Evidence caveat only: published SARM liver injury case reports very frequently involve multi-ingredient or multi-compound exposures, which confounds causality attribution to any single agent and makes the case literature a weak basis for compound-level risk ranking. |
Handling information describes laboratory practice for a research reagent. It is not a preparation guide for use in humans.
the receipts
6 citedLiverTox: Clinical and Research Information on Drug-Induced Liver Injury, NIDDK/NIH · 2024 · official
U.S. Food and Drug Administration · 2025 · official
Current Oncology Reports · 2016 · randomized
GTx Inc. company announcement (reported via FierceBiotech) · 2013 · randomized
The Lancet Oncology · 2013 · randomized
others in Anabolic & Receptor