RAD-140 (Testolone)

Identity, and four names for one molecule

Despite the company it keeps, RAD140 is not a peptide, and its identity resolves cleanly. PubChem holds a single compound record under that name: CID 44200882, CAS 1182367-47-0, molecular formula C20H16ClN5O2, molecular weight 393.8 g/mol, InChIKey XMBUPPIEVAFYHO-KPZWWZAWSA-N, UNII 4O87Q44KNC. The FDA Global Substance Registration System agrees on the formula for that UNII and computes a weight of 393.827. The IUPAC name on the PubChem record, 2-chloro-4-[[(1R,2S)-1-[5-(4-cyanophenyl)-1,3,4-oxadiazol-2-yl]-2-hydroxypropyl]amino]-3-methylbenzonitrile, describes a nonsteroidal small molecule built around a 1,3,4-oxadiazole ring, carrying two nitrile groups and a chlorinated benzonitrile head.

Four further designations attach to that same record. Testolone is the name the consumer market uses. Vosilasarm is the International Nonproprietary Name and the USAN, registered under INN number 11230 and USAN code MN-282. EP-0062 is the code carried by the current clinical programme. Radius Health described the molecule in 2011, the first-in-human trial was sponsored by Stemline Therapeutics, and the trial now recruiting is sponsored by Ellipses Pharma. Secondary pages routinely treat the oncology programme and the powder sold online as two separate subjects. Both chemical registries index every one of those names to the same substance.

No medicines regulator has approved this molecule for any indication anywhere. The FDA's consumer update on selective androgen receptor modulators states that they are not FDA approved, that although they are often marketed as dietary supplements or sold for research use only they are considered unapproved drugs, and that they cannot be legally marketed in the United States as a dietary supplement or drug.

What the 2011 discovery paper measured

Miller and colleagues published the discovery paper in ACS Medicinal Chemistry Letters in 2011. Binding affinity for the androgen receptor was reported as Ki 7 nM, against 29 nM for testosterone and 10 nM for dihydrotestosterone in the same assay. The closest off-target receptor was the progesterone receptor at IC50 750 nM. Functional agonist activity in the C2C12 osteoblast differentiation assay gave an EC50 of 0.1 nM, with DHT at 0.05 nM. Oral bioavailability was given as 27 to 63 percent in rats and 65 to 75 percent in monkeys.

Two rat experiments followed the standard Hershberger design. In castrated immature males dosed orally for eleven days, five per group, levator ani weight rose from 0.03 mg/kg and reached the sham-operated control level at 0.3 mg/kg, while prostate weight stayed below the response to subcutaneous testosterone propionate at every dose tested. In intact young males, eight per group over the same eleven days, levator ani weight rose above control from the lowest dose tested, and prostate weight did not exceed the intact control until 30 mg/kg. Separation between those two thresholds is the paper's central result.

Primate work was smaller. Three young intact male cynomolgus monkeys per group received 0.01, 0.1 or 1.0 mg/kg orally for 28 days, followed by 21 days off drug. Mean body weight rose more than 10 percent at 0.1 mg/kg. DEXA scans taken two days before dosing and one day after the last dose showed no consistent effect on fat mass and what the authors called a qualitative trend in lean tissue; the paper states that none of the tissue weight increases reached statistical significance, and attributes that to the group size of three and large standard deviations. Total plasma testosterone fell from roughly 600 to 800 ng/dL at baseline to roughly 200 to 300 ng/dL in all three groups, significantly so only in the lowest-dose group.

Liver chemistry in that monkey study was unremarkable. No animal at any dose showed transaminase elevation greater than twofold over its own baseline. The paper closes by stating that the compound was being prepared for phase 1 studies in cancer cachexia. No such trial appears in ClinicalTrials.gov.

The human record is oncology, and it is small

Preclinical work set up the oncology programme. Yu and colleagues, publishing in Clinical Cancer Research in 2017, reported that orally administered RAD140 bound the androgen receptor with high affinity, activated it in breast cancer but not prostate cancer cells, and inhibited growth in androgen-receptor and oestrogen-receptor positive patient-derived xenograft models, alone and in combination with palbociclib, with repression of the ESR1 gene offered as the mechanism.

NCT03088527 opened in October 2017 and completed in September 2020, sponsored by Stemline Therapeutics, in postmenopausal women with hormone-receptor-positive breast cancer. The registry records 20 participants as the actual enrolment. LoRusso and colleagues, publishing the trial in Clinical Breast Cancer in 2022, report 22 enrolled, of whom 21 were androgen-receptor positive. Two figures for one study; this record does not reconcile them, and the numbers below follow the published paper, which is the more detailed account.

Dose levels were 50 mg once daily in six patients, 100 mg in thirteen and 150 mg in three, with 100 mg identified as the maximum tolerated dose and a half-life of 44.7 hours supporting once-daily administration. The most frequent treatment-emergent adverse events were elevated AST in 59.1 percent, elevated ALT in 45.5 percent and elevated total bilirubin in 27.3 percent, with vomiting, dehydration, decreased appetite and weight loss each at 27.3 percent. Grade 3 or 4 events occurred in 16 of 22 patients. Sex hormone binding globulin fell in 18 of 18 patients measured and prostate-specific antigen rose in 16 of 20, which the authors read as target engagement. One patient had a partial response, clinical benefit rate at 24 weeks was 18.2 percent, and median progression-free survival was 2.3 months.

A second trial, NCT05573126, has been recruiting since January 2023 under Ellipses Pharma, testing the molecule as EP0062 alone and in combination with elacestrant, everolimus, abemaciclib, fulvestrant or exemestane in the same tumour type. The registry gives an estimated enrolment of 95 and a completion date of February 2028; the sponsor's own announcement of the trial design at the San Antonio Breast Cancer Symposium on 5 December 2022 said recruitment had commenced for up to 130 patients globally. Findings so far exist only as conference abstracts, including one presented at ASCO in 2025. Conference abstracts are not peer-reviewed publications, and the ASCO abstract page returned HTTP 403 to retrieval attempts made for this record.

Liver injury, and what the case reports have in common

Transaminase elevation in the phase 1 trial recurs across the case literature, in younger people, at exposures nobody recorded. Barbara and colleagues published the first indexed report in 2020: a 52-year-old man who had taken two supplements, one containing RAD-140 and one containing RAD-140 and LGD-4033. Liver biopsy showed diffuse centrilobular canalicular cholestasis, a prominent ductular reaction and mild lobular inflammation with a rare non-necrotising epithelioid granuloma. Liver enzymes returned to normal roughly three months after he stopped both products.

Several reports since have described the same cholestatic pattern. Leung and colleagues in 2022 reported a 24-year-old man with a peak total bilirubin of 38.5 mg/dL after five weeks of use, with biopsy showing intracytoplasmic and canalicular cholestasis and minimal portal inflammation, resolving after cessation. Ladna and colleagues in 2023 reported a 26-year-old man whose liver panel normalised at two months. Niazi and colleagues in 2025 reported prolonged cholestasis managed with corticosteroids. Dao and colleagues in 2026 reported a previously healthy young man taking a product containing RAD-140 and andarine whose progressive hyperbilirubinaemia required plasmapheresis, with a course complicated by pancreatitis and acute kidney injury; the authors describe it as the most severe presentation reported to date.

Three further indexed reports show the pattern is not uniform. Mohamed and colleagues in 2023 described a 22-year-old man whose biopsy showed mixed portal hepatitis, cholestasis and biliary reactive changes, with total bilirubin falling from a peak of 530 micromol/L to 188 micromol/L at one month. Perananthan and George in 2024 described a 43-year-old man with a mixed cholestatic and hepatotoxic picture and a serum bilirubin of 708 micromol/L on admission. Demangone and colleagues in 2024 described a 29-year-old man with jaundice after three months of use whose liver ultrasound showed hepatic steatosis and a hyperechoic lesion rather than a cholestatic picture, resolving after cessation.

Vignali and colleagues searched four databases in November 2022 and included 33 studies covering 2,136 participants, 1,447 of them exposed to some SARM. Across every compound in that review there were 15 drug-induced liver injury case reports, one Achilles tendon rupture and one rhabdomyolysis, with elevated ALT reported at a mean of 7.1 percent across clinical trials. Case reports establish that something happened; they cannot establish how often, because the denominator is unrecorded. Several of the reports above also involve multi-ingredient products, so the exposure being described is a mixture rather than a molecule.

Cardiac and endocrine reports

Three cardiac case reports name this compound. Padappayil and colleagues described acute myocarditis in a young man in a 2022 report in Cureus. Schwartzman and colleagues described myopericarditis in a 16-year-old boy following a first dose, published in JACC: Case Reports in 2024. Skorupski and colleagues described heart failure in Polish Archives of Internal Medicine the same year. Each is a single patient, none establishes frequency, and in each the compound's contribution is inferred from timing and from the absence of another explanation.

Endocrine effects appear in one report with unusually thorough product analysis. Chong and colleagues described a 40-year-old man with bilateral gynaecomastia and biochemical hypogonadotropic hypogonadism after six months of taking three commercial supplements. Analysis found RAD-140, the growth hormone secretagogue MK-677 and cardarine in those products, and also detected undisclosed testosterone, oestradiol and growth hormone in all three, plus an unidentified compound co-eluting near the testosterone peak. Symptoms and biochemistry resolved on cessation. What that report documents is an outcome following exposure to a mixture containing undeclared hormones, which is a different object from an outcome following exposure to one characterised molecule.

Rodent ageing work, and a split by sex

Rodent ageing studies point in different directions depending on the sex of the animal. Brown and colleagues gave 5 mg/kg to young and adult female mice for ten weeks and measured strength, recovery from eccentric contractions, frailty status and mortality risk. Frailty and mortality risk rose in both treated groups relative to controls, at p values of 0.042 or lower; adaptive potential fell in the young group (p = 0.040) but not the adult group (p = 0.688), and torque did not differ after two to three weeks of recovery.

Heinze and colleagues treated older C57BL/6 mice, 21 males and 15 females aged 23.7 to 25.5 months, with the same 5 mg/kg daily for six weeks. Frailty did not differ between treated and control animals in either sex. Male mice showed preserved lean mass (p = 0.024), preserved bone mineral density (p = 0.004) and lower serum interleukin-6 (p = 0.043); female mice showed neither the body-composition nor the inflammatory change. Grip strength, fat mass and the skeletal muscle genes assayed were unaffected in both sexes.

Heinze and colleagues followed that work with a 2026 report in GeroScience, echocardiographing 23-month-old male and female mice on the same 5 mg/kg daily schedule for six weeks. Ejection fraction was higher by 10.4 percent, stroke volume by 9.6 microlitres and cardiac output by 4.5 mL/min in treated animals of both sexes, while myocardial strain (-5.8 percent) and isovolumic relaxation time (-4.7 ms) improved in males and showed lesser or opposite changes in females. Higher interleukin-6 correlated with worse global circumferential strain in males but not females. Left ventricular androgen receptor mRNA was lower with treatment in both sexes, and no structural differences were observed.

Muscle work in rats supplies a fourth reading. Puskas and colleagues randomised male Sprague-Dawley rats, ten per group, to RAD140 or vehicle methylcellulose delivered in drinking water, with or without functional overload of the plantaris, for fourteen days. Muscle weight rose markedly in the treated overload group but was not statistically different from the vehicle overload group. Fibre cross-sectional area was significantly elevated in the treated control group against the vehicle control. Micro-computed tomography showed no effect on cortical or trabecular bone morphometry at fourteen days.

What is sold under the name, and where it stands

Two analytical studies bear on what the name actually buys. Van Wagoner and colleagues purchased 44 products marketed as SARMs over the internet in 2016 and analysed them under chain of custody. Twenty-three, or 52 percent, contained a selective androgen receptor modulator, and the three detected were ostarine, LGD-4033 and andarine. RAD140 was not among the compounds found. Seventeen products, 39 percent, contained a different unapproved drug, four contained no active compound at all, and the amount present matched the label in 18 of the 44. That paper carries an erratum printed in JAMA in February 2018, which does not alter those figures.

Gaudiano and colleagues repeated the exercise on 13 products bought from retail sites accessible in Italy, publishing in Sexual Medicine in 2024. The stated SARM was present in about 70 percent of samples; in 23 percent a different SARM was present instead; one sample contained none. Undeclared tamoxifen, clomifene, testosterone, epimethandienone or tadalafil were measured in 30 percent of samples, more than one active substance was present in over 60 percent, and quantitative NMR put content between 30 and 90 percent of the label claim.

Anti-doping and regulatory positions are explicit. The 2026 WADA Prohibited List places selective androgen receptor modulators under S1.2, Other Anabolic Agents, and names RAD140 among its examples; the whole S1 class is prohibited at all times, in and out of competition, and is non-specified. The FDA's consumer update on this class names heart attack and stroke, psychosis or hallucinations, sleep disturbance, sexual dysfunction, liver injury and acute liver failure, infertility, pregnancy miscarriage and testicular shrinkage among the harms reported to it.

What is not known

The published record does not establish what this molecule does in healthy men, which is the population that actually consumes it. Both registered trials enrolled postmenopausal women with breast cancer; the phase 1 was 22 patients, heavily pretreated, followed for a median progression-free survival of 2.3 months. No study has characterised effects on lean mass, strength, bone density, endogenous gonadal function or lipids in healthy human subjects of either sex, and no trial has run long enough to say anything about chronic exposure. The frequency of liver injury is unknown: the eight indexed case reports establish a recurring, mostly cholestatic picture, but no denominator exists, one report describes a steatotic rather than cholestatic pattern, and several of the reported cases involve products containing more than one compound, sometimes including undeclared hormones. No published study has measured aromatisation, fertility effects, carcinogenicity or reproductive toxicity for this molecule. Rodent ageing work has produced sex-divergent results that no one has yet reconciled, with one study reporting increased frailty and mortality risk in females and another reporting preserved lean mass and bone density in males at the same dose. Whether the reformulated clinical material used in the current Ellipses trial behaves pharmacokinetically like the powder sold online is not addressed by any published comparison; the registries index both to one chemical structure, which is a statement about the molecule and not about a product.

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