Ostarine Enobosarm between cancer cachexia, breast programmes, and GLP-1 lean-mass preservation

01 Names, chemistry, and identity traps

Enobosarm is a nonsteroidal arylpropionamide selective androgen receptor modulator. Synonyms that must resolve to the same chemical object before a paper is admitted include ostarine, MK-2866, GTx-024, S-22 and VERU-024. PubChem and registry designations are cross-checked; community bottle labels are not identity. It is not andarine (S-4 / GTx-007), not ligandrol (LGD-4033), not RAD140 / vosilasarm, and not Cardarine (GW501516), a PPAR‑δ agonist that shares retail shelves but not the AR mechanism. The axonal NADase enzyme SARM1 is a different molecule entirely and is excluded from this document.

Open PubMed counts for the compound query enobosarm OR ostarine OR GTx-024 OR MK-2866 were on the order of one hundred fifteen indexed records at the 5 August 2026 harvest — denser than any other SARM in this commission, thinner than a mature approved anabolic drug. That asymmetry is the first fact of the monograph: there is a real clinical residue, and it is still a small literature.

02 Mechanism claims and what they do not prove

As an AR ligand designed for tissue selectivity, enobosarm is claimed to favour muscle and bone anabolism over prostate and skin androgenicity in preclinical models (Dalton and colleagues’ SARM programme literature; reviews such as Narayanan et al., 2018). In reporter and animal systems the selectivity story is comparative — less prostate stimulation than a reference androgen at a lean-mass-effective exposure — not an absolute firewall. Human selectivity is inferred from endpoint patterns (lean mass, lipids, PSA, skin/hair adverse events) rather than proven as a universal property of every exposure context.

Drug–drug interaction work on GTx-024 mapped CYP3A4 inhibition (itraconazole), CYP3A4 induction (rifampin), UGT inhibition (probenecid), and probe substrates (celecoxib, rosuvastatin) in open-label Phase I designs (PMID 27105861). Those studies belong to pharmaceutical development hygiene; they are not grey-market stacking advice and are not restated here as use instructions.

03 Older adults and cancer-related muscle wasting

Dalton and colleagues reported that GTx-024 improved lean body mass and physical function in healthy elderly men and postmenopausal women in a randomised design that helped establish enobosarm as a clinical SARM rather than a purely preclinical tool (PMID 22031847). The abstract framing emphasises tissue-selective anabolic effects on muscle and bone with sparing of classical androgenic tissues — the class promise stated as a clinical hypothesis.

Dobs et al. (2013) enrolled male (>45 years) and postmenopausal female patients with cancer who were not obese and who had at least 2% weight loss in the previous six months into a double-blind, placebo-controlled Phase 2 trial of once-daily oral enobosarm 1 mg, 3 mg, or placebo for 113 days (PMID 23499390; Lancet Oncology). The study assessed efficacy and safety against cancer-induced muscle wasting. Lean mass and related endpoints moved in the direction expected from the SARM programme; functional wins were harder and remain the recurring design problem of the class. Srinath and Dobs (2014) summarised enobosarm as a potential cachexia treatment in a secondary review (PMID 24490605) — useful context, not a substitute for the RCT primary paper.

Later NSCLC Phase 3 efforts (POWER-type programmes under successive sponsors) belong in the programme history as ambition and attrition. Registry status and business-versus-science stop reasons must be re-checked at each reissue; this monograph does not treat a terminated Phase 3 as a settled negative efficacy verdict without the published package in hand.

04 AR-positive breast-cancer programmes

The androgen receptor can act as a tumour suppressor in oestrogen receptor–positive breast cancer. Palmieri and colleagues evaluated activity and safety of oral enobosarm in postmenopausal women with previously treated ER-positive, HER2-negative, AR-positive locally advanced or metastatic breast cancer in a randomised, open-label, multicentre Phase 2 trial across thirty-five centres in nine countries (PMID 38342115; Lancet Oncology, 2024). That paper is the peer-reviewed oncology island for enobosarm in this harvest. Earlier conference abstracts and Fast Track communications are secondary until they collapse into full texts. At least one prior Phase 3 breast effort was terminated for business rather than purely scientific reasons; registry status is not frozen into this PDF as eternal truth.

Oncology endpoints are not physique endpoints. A clinical benefit rate in AR-positive metastatic disease does not license bodybuilding use, and grey-market “ostarine” bottles are not the trial capsules used in breast protocols.

05 QUALITY — registry facts versus sponsor toplines

ClinicalTrials.gov study NCT06282458 (“Dose-Finding Study Evaluating Effect on Body Composition of Enobosarm in Patients Taking a GLP-1 for Chronic Weight Mgmt”) is a Phase 2 interventional, randomised, parallel, triple-masked trial. The ClinicalTrials.gov API v2 harvest (5 August 2026) lists overall status COMPLETED, actual enrollment 168, actual start 29 April 2024, primary completion 11 April 2025, and study completion 22 August 2025. Subjects medically indicated for a GLP-1 receptor agonist for weight management were randomised 1:1:1 to enobosarm 3 mg, enobosarm 6 mg, or placebo; the first GLP-1 dose was Day 1 of the study. The primary efficacy endpoint is percentage change from baseline in total lean body mass by DEXA at 112 days. Subjects continued enobosarm or matching placebo monotherapy from Day 112 to Day 196 to assess lean mass, muscle mass, weight-loss maintenance, and rebound fat gain after GLP-1 discontinuation.

Veru press releases and investor communications claiming lean-mass preservation and greater fat loss are recorded in the harvest as discovery leads. They remain secondary until a peer-reviewed full text is admitted. This monograph therefore states the registry design with confidence and withholds numerical topline efficacy claims that have not passed peer review.

06 Axis, lipids, and what short trials show

Class-level hypothalamic–pituitary–gonadal and HDL effects appear whenever they are carefully measured in short SARM trials. Enobosarm programmes are not exempt from that reading even when a particular paper emphasises tolerability. The honest comparison is to other oral AR ligands and to anabolic-androgenic steroids, not to an imagined “non-hormonal” supplement. Milligram amounts used in trials are study parameters; they are not transcribed here as use advice.

07 Drug-induced liver injury and product identity

LiverTox’s SARM chapter (NBK619971; Camoufox harvest noting a 20 September 2025 update) frames consumer SARM exposure as a cause of severe cholestatic jaundice resembling anabolic-steroid jaundice, while noting that no SARM was approved for human use. Case reports and series naming ostarine- or enobosarm-labelled products appear in the peer-reviewed and clinical-journal literature (examples surfaced in the harvest include DILI case reports indexed around PMC8337042 / related enobosarm DILI titles; class reviews PMID 38059982 and 35340496). Two variables must stay in the same sentence: (1) pharmaceutical trial material at protocol exposures often showed quiet aminotransferase profiles over limited durations; (2) consumer cases frequently involve unverified product identity, multi-agent stacks, and labelled amounts far from Phase 2 oncology or cachexia protocols. A bottle that says “ostarine” is not Dobs 2013 study drug until analytics say so.

08 Regulatory and anti-doping status

Enobosarm is not FDA-approved for bodybuilding, physique enhancement, or aging. Selective androgen receptor modulators are listed by the World Anti-Doping Agency under S1 Anabolic Agents. FDA consumer updates and warning letters on body-building products containing SARMs apply to the market context in which “ostarine” is sold. Those regulatory facts are independent of Research Use Only stamps on grey-market labels.

09 Grey-market fog

Analytical surveys of research-chemical SARMs have found under-dosing, over-dosing, mislabelling, and undeclared second agents. That literature is market-behaviour evidence. It means that spontaneous case reports and forum pharmacokinetics cannot be casually mapped onto GTx-024 or VERU-024 trial pharmacokinetics. Sibling monographs on ligandrol and RAD140 return to the same identity problem wherever DILI is discussed.

10 What is not in the admitted record

Independent long-term randomised trials of grey-market ostarine products do not exist. A peer-reviewed primary publication of QUALITY efficacy and safety tables was not admitted at the 5 August 2026 harvest; registry completion is not a results paper. Functional endpoints remain harder than lean-mass endpoints across the historical cachexia programmes. Cardiovascular outcome trials of enobosarm do not underpin the grey-market conversation. Head-to-head comparisons of enobosarm versus testosterone or versus other SARMs on hard clinical outcomes in the same protocol are sparse.

In-vitro cytotoxicity observations (for example sex-specific cardiomyocyte findings indexed in the harvest) are mechanistic signals, not clinical dosing guides, and are not expanded here into causal claims about human cardiac risk without clinical confirmation.

11 How this monograph sits beside the class document

The SARMs class monograph (No. 86 in the filing plan) maps shared pharmacology, shared DILI themes, WADA/FDA status, and the Cardarine identity trap. This compound document carries molecule-specific trial history: Dobs 2013, Palmieri 2024, QUALITY registry architecture, and the enobosarm-named case layer. Readers who need the shelf overview start with the class document; readers who need the molecule stay here.

How this document was assembled

Commissioned 5 August 2026 in the Adjacent Compounds / SARMs group and rewritten the same day after a deep research-API harvest. Sources: PubMed via NCBI E-utilities (counts, esummary, efetch abstracts); Tavily and Exa discovery queries; ClinicalTrials.gov API v2 for NCT06282458; Camoufox fetch of LiverTox NBK619971; FDA and WADA public pages; Phase A packets under projects/adjacent_compounds_research_2026/. Firecrawl returned empty markdown for several PubMed and registry URLs and was not treated as negative evidence. HOUSE_STYLE governs presentation. PubMed-indexed references are NCBI-resolved in manifest/05_references.json.

Evidence handling

Study type is named in the reporting sentence. Animal and in-vitro results are not phrased as human outcomes. QUALITY sponsor toplines are labelled secondary. Consumer DILI cases are labelled as grey-market exposure literature unless product analytics accompany the report. Conflicting trial-versus-case safety signals are presented as conflict with product identity as the bridging variable.

References

1. Coss CC, Jones A, Dalton JT. Pharmacokinetic drug interactions of the selective androgen receptor modulator GTx-024(Enobosarm) with itraconazole, rifampin, probenecid, celecoxib and rosuvastatin. Invest New Drugs. 2016;34(4):458-67.
   PMID 27105861 · doi:10.1007/s10637-016-0353-8
2. Dalton JT, Barnette KG, Bohl CE, Hancock ML, Rodriguez D, Dodson ST, et al.. The selective androgen receptor modulator GTx-024 (enobosarm) improves lean body mass and physical function in healthy elderly men and postmenopausal women: results of a double-blind, placebo-controlled phase II trial. J Cachexia Sarcopenia Muscle. 2011;2(3):153-161.
   PMID 22031847 · doi:10.1007/s13539-011-0034-6 · PMC3177038
3. Dobs AS, Boccia RV, Croot CC, Gabrail NY, Dalton JT, Hancock ML, et al.. Effects of enobosarm on muscle wasting and physical function in patients with cancer: a double-blind, randomised controlled phase 2 trial. Lancet Oncol. 2013;14(4):335-45.
   PMID 23499390 · doi:10.1016/S1470-2045(13)70055-X · PMC4898053
4. Dubois V, Simitsidellis I, Laurent MR, Jardi F, Saunders PT, Vanderschueren D, et al.. Enobosarm (GTx-024) Modulates Adult Skeletal Muscle Mass Independently of the Androgen Receptor in the Satellite Cell Lineage. Endocrinology. 2015;156(12):4522-33.
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6. Leciejewska N, Pruszyńska-Oszmałek E, Nogowski L, Sassek M, Strowski MZ, Kołodziejski PA. Sex-specific cytotoxicity of ostarine in cardiomyocytes. Mol Cell Endocrinol. 2023;577:112037.
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7. Leciejewska N, Jędrejko K, Gómez-Renaud VM, Manríquez-Núñez J, Muszyńska B, Pokrywka A. Selective androgen receptor modulator use and related adverse events including drug-induced liver injury: Analysis of suspected cases. Eur J Clin Pharmacol. 2024;80(2):185-202.
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8. Palmieri C, Linden H, Birrell SN, Wheelwright S, Lim E, Schwartzberg LS, et al.. Activity and safety of enobosarm, a novel, oral, selective androgen receptor modulator, in androgen receptor-positive, oestrogen receptor-positive, and HER2-negative advanced breast cancer (Study G200802): a randomised, open-label, multicentre, multinational, parallel design, phase 2 trial. Lancet Oncol. 2024;25(3):317-325.
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9. Solomon ZJ, Mirabal JR, Mazur DJ, Kohn TP, Lipshultz LI, Pastuszak AW. Selective Androgen Receptor Modulators: Current Knowledge and Clinical Applications. Sex Med Rev. 2019;7(1):84-94.
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10. Srinath R, Dobs A. Enobosarm (GTx-024, S-22): a potential treatment for cachexia. Future Oncol. 2014;10(2):187-94.
    PMID 24490605 · doi:10.2217/fon.13.273
11. ClinicalTrials.gov. NCT06282458 — QUALITY / enobosarm + GLP-1 body composition. Protocol inventory via API v2.
    https://clinicaltrials.gov/study/NCT06282458
12. NIDDK LiverTox. Selective Androgen Receptor Modulators (SARMs). NBK619971 (Camoufox harvest 5 August 2026).
    https://www.ncbi.nlm.nih.gov/books/NBK619971/
13. U.S. Food and Drug Administration. Consumer updates and warning letters on body-building products containing SARMs. Regulatory context.
    https://www.fda.gov/
14. World Anti-Doping Agency. Prohibited List — S1 Anabolic Agents (selective androgen receptor modulators).
    https://www.wada-ama.org/
15. NIDDK LiverTox. Selective Androgen Receptor Modulators (SARMs). NCBI Bookshelf NBK619971.
    https://www.ncbi.nlm.nih.gov/books/NBK619971/
16. ClinicalTrials.gov. Protocol inventory via API v2; not peer-reviewed results.
    https://clinicaltrials.gov/
17. PubChem compound summary pages used for identity cross-checks.
    https://pubchem.ncbi.nlm.nih.gov/