What it is
RAD-140 (Testolone, Vosilasarm, Ellipses code EP0062; CAS 1182367-47-0, PubChem CID 44200882, molecular formula C20H16ClN5O2, MW 393.83 g/mol) is a nonsteroidal selective androgen receptor modulator designed by Miller and colleagues at Radius Health and first published in ACS Medicinal Chemistry Letters in 2011. The compound is built on a benzonitrile core bearing a 1,3,4-oxadiazole linker and a chiral (1R,2S)-hydroxypropyl amino bridge. It binds the androgen receptor with Ki of approximately 7 nM — comparable to testosterone (29 nM) and dihydrotestosterone (10 nM) — and shows greater than 100-fold selectivity over the progesterone receptor. Because it is nonsteroidal, it is not a substrate for aromatase and does not produce estradiol on-target. Development for sarcopenia, cancer cachexia, and osteoporosis was discontinued by Radius Health; the asset was licensed to Ellipses Pharma as EP0062 for continued investigation in AR+/ER+/HER2- metastatic breast cancer. It is sold as a research chemical only and is not approved for human use by any regulator.
In plain English
RAD-140 (also called Testolone) is a synthetic drug made in a lab to act like testosterone at specific receptors — mainly in muscle and bone — while hopefully affecting the prostate less. The technical term for this type of drug is "selective androgen receptor modulator" or SARM. It was invented around 2011 by Radius Health. It is NOT a peptide and NOT a supplement — it's an unapproved investigational drug. It was tested in a breast cancer clinical trial because certain breast cancers grow in response to androgen and estrogen, and RAD-140 can interfere with both signals. An Alzheimer's drug trial also started but was discontinued early. No regulator anywhere has approved it for any medical use.
How it works
- 01
Androgen receptor agonism with tissue-selective coregulator recruitment
Miller (2011, ACS Med Chem Lett) described the original medicinal-chemistry rationale: full AR agonism in anabolic tissue (skeletal muscle, bone) with minimal agonist activity in prostate. In castrated rat models the compound increased levator ani mass at doses that produced little prostate weight gain — the defining SARM pharmacological signature. The molecular basis is differential coregulator recruitment: ligand-specific AR conformational states recruit different coactivator/corepressor complexes in different tissues, producing tissue-selective transcriptional programs. No human receptor-occupancy or tissue-distribution PK has been published.
In plain English
Acts like testosterone in muscle and bone — with less prostate effect (in animals)
RAD-140 binds the same receptor that testosterone does — the androgen receptor — but the drug's shape causes that receptor to behave differently in different tissues. In castrated rat studies, it built up the levator ani muscle without enlarging the prostate much. That "muscle yes, prostate no" pattern is the entire scientific basis for SARM marketing. The tissue-selectivity happens because the drug triggers a slightly different receptor shape, which attracts different helper proteins depending on where in the body you are. This selective effect has NOT been confirmed in healthy adult humans.
- 02
AR-mediated repression of ESR1 in AR+/ER+ breast cancer
Wagoner (2017, Clin Cancer Res) showed that in AR+/ER+ breast-cancer patient-derived xenografts, RAD-140 acts as a potent AR agonist whose activated AR occupies regulatory regions of the ESR1 gene and represses ER-alpha expression. The resulting dual effect — AR activation plus ER suppression — inhibits tumor growth as monotherapy and additively with the CDK4/6 inhibitor palbociclib in PDX models. This is the mechanism that carried the compound into the NCT03088527 Phase 1 and justifies continued development under EP0062.
In plain English
How it attacks a specific type of breast cancer
Most breast cancers grow because of estrogen. Some also respond to androgens (male hormones). In 2017, researchers showed that RAD-140 activates the androgen receptor — and when that happens, the activated receptor turns OFF the gene that makes the estrogen receptor. So one drug suppresses two cancer-growth signals at once. In mice implanted with human breast cancer tumors, it worked as a standalone treatment and was even better combined with a common cancer drug (palbociclib). This double-action is why it entered the human breast cancer trial.
- 03
AR / MAPK-ERK-mediated neuroprotection
Jayaraman (2014, Endocrinology) demonstrated that in cultured rat hippocampal neurons, RAD-140 protected against apoptosis induced by β-amyloid peptide and apoptosis activator II at potency comparable to testosterone. The effect was AR-dependent (blocked by AR antagonists) and required MAPK/ERK signaling (abolished by the MEK inhibitor U0126, with concomitant loss of ERK phosphorylation). In gonadectomized male rats with kainate-induced hippocampal excitotoxic lesions, systemically administered RAD-140 crossed the blood-brain barrier, activated androgenic gene programs in neural tissue, and reduced neuronal loss while sparing prostate weight. This mechanistic dataset supported the MK-0567 Alzheimer's-disease program, which did not progress.
In plain English
Possible brain protection — animal research only
In rats and cell experiments, RAD-140 protected brain cells from two types of damage similar to what happens in Alzheimer's disease. The protection worked through the androgen receptor and a cell-survival signaling chain. The drug crossed from the bloodstream into the brain and reduced nerve cell death in rats without enlarging their prostate. An Alzheimer's drug trial was started based on this promising data — and then shut down before any results were published. No human brain or cognition data exists.
- 04
Hepatic metabolism and the hepatotoxicity signal
The Phase 1 in metastatic breast cancer (NCT03088527) defined the MTD at 100 mg/day and identified hepatocellular injury as the dose-limiting toxicity: AST elevation in 59.1% of patients, ALT 45.5%, total bilirubin 27.3%. The specific CYP450 isoforms responsible for RAD-140 biotransformation have not been published in peer-reviewed form. The clinical-trial hepatotoxicity pattern converges with the unregulated-use DILI case literature (Flores 2020 NEJM, Leciejewska 2022 review, Barbara 2020) describing cholestatic and mixed-pattern drug-induced liver injury — including cases requiring hospitalization — in otherwise healthy young men taking RAD-140 or related SARMs from online sources.
In plain English
Why it damages the liver
In the breast cancer trial, liver damage was the main reason doses couldn't go higher — over half the patients had elevated liver enzymes at the maximum tolerated dose. Exactly how the drug harms the liver hasn't been published. Outside the trial, multiple healthy young men buying RAD-140 online have ended up hospitalized with serious liver injury: jaundice (yellowing of the skin and eyes), high liver enzymes, and a pattern called cholestatic injury where bile can't flow properly. This same liver-damage pattern has been reported across multiple SARMs.
- 05
HPG-axis suppression (expected but undercharacterized)
Because RAD-140 is an AR agonist, it produces negative feedback at the hypothalamus and pituitary, suppressing GnRH pulsatility, luteinizing hormone, follicle-stimulating hormone, and consequently endogenous testosterone. The NCT03088527 postmenopausal-female population does not allow direct measurement of this effect in eugonadal males. The Leciejewska 2022 review summarizes the published SARM HPG-axis data across the class: reductions in LH/FSH/total testosterone are reproducible at bodybuilding-market doses, with recovery timelines on the order of weeks to months that have not been formally characterized for RAD-140 specifically.
In plain English
It shuts down your body's natural testosterone production
When you take a drug that acts like testosterone at receptors throughout your body, your brain detects the signal and tells the body to make less real testosterone. It's the same shutdown that happens with anabolic steroids. The brain thinks there's enough, so it stops sending signals to the testes. The clinical trial was in postmenopausal women, so this couldn't be measured directly. But case reports and reviews of male SARM users document drops in LH, FSH, and total testosterone. How long recovery takes after stopping is not formally studied for RAD-140.
- 06
What is NOT known about the mechanism or its human consequences
No formal human pharmacokinetic profile is in the peer-reviewed literature (absorption, tissue distribution, elimination half-life, metabolite identities). The CYP enzymology is not published. Off-target nuclear-receptor activity has been characterized only in vitro. The Brown 2023 female-mouse finding — chronic 5 mg/kg worsened frailty and mortality relative to controls rather than improving musculoskeletal outcomes — is unexplained and has not been reconciled with the earlier castrated-rat preclinical signature. Whether the tissue selectivity observed in rodents translates to the human prostate at chronic bodybuilding-market doses is unknown.
In plain English
What we still don't understand about how it works in people
No formal human pharmacokinetics study has been published — we don't know the drug's exact half-life in humans, how it distributes in tissues, what breakdown products it makes, or which liver enzymes process it. The 2023 finding that RAD-140 worsened frailty and raised death risk in female mice has not been explained and contradicts the earlier rat data. The "selective" muscle vs. prostate effect shown in castrated rats has never been tested in a controlled study of healthy human adults. Whether it applies at the doses people actually use is completely unknown.