Rad-140 effects

The most revealing thing about RAD-140 isn't what it does in muscle tissue—it's how cleanly it avoids the prostate. In rodent studies, this selective androgen receptor modulator (SARM) produced the anabolic effects of testosterone while leaving prostate weight essentially unchanged, a profile that separates it from conventional androgens and explains why it advanced to Phase I human trials.

RAD-140: A Nonsteroidal Compound Designed to Bind Androgen Receptors Without the Steroidal Backbone

RAD-140 (also called testolone) belongs to the selective androgen receptor modulator class—compounds engineered to activate androgen receptors in muscle and bone tissue while minimizing androgenic effects in reproductive tissues. Developed by Radius Health, Inc., RAD-140 emerged from structure-activity relationship studies aimed at creating a nonsteroidal androgen receptor ligand with tissue-selective properties.

The compound's structure differs fundamentally from testosterone: it lacks the four-ring steroid backbone. Instead, RAD-140 uses a benzonitrile scaffold with a piperazine ring, giving it high oral bioavailability and a binding affinity for the androgen receptor comparable to testosterone itself. This structural design allows RAD-140 to function as an agonist in some tissues while behaving more like a partial agonist or antagonist in others—tissue selectivity driven by conformational changes in the receptor complex and differential recruitment of coactivator proteins.

Radius Health initially explored RAD-140 as a potential treatment for muscle wasting in cancer cachexia and age-related sarcopenia. The compound entered Phase I clinical trials to evaluate safety and pharmacokinetics in healthy volunteers, though publicly available data from those trials remains limited. As of 2026, RAD-140 has not advanced to Phase II efficacy trials for any medical indication, and the FDA has not approved it for therapeutic use. For research purposes only, the compound remains available through research chemical vendors serving the investigational peptide and SARM community.

How RAD-140 Selectively Activates Androgen Receptors Through Tissue-Specific Cofactor Recruitment

RAD-140 functions by binding to the androgen receptor, a nuclear hormone receptor that regulates gene transcription. When an androgen receptor ligand binds, the receptor undergoes a conformational change, dissociates from heat shock proteins, dimerizes, and translocates to the nucleus where it binds androgen response elements on DNA. This initiates transcription of genes involved in protein synthesis, satellite cell activation, and nitrogen retention.

The selectivity comes from how different tissues respond to the same receptor activation. In skeletal muscle, RAD-140 binding promotes recruitment of coactivator proteins like SRC-1 and TIF2, which enhance transcriptional activity and drive anabolic effects. In prostate tissue, the same RAD-140-receptor complex recruits a different set of cofactors—or recruits them less efficiently—resulting in weaker transcriptional activation. This tissue-specific cofactor recruitment pattern, determined by the three-dimensional shape of the ligand-receptor complex, explains why RAD-140 can stimulate muscle growth without proportionally enlarging the prostate.

Downstream effects in muscle tissue include upregulation of myogenic regulatory factors, increased myofibrillar protein synthesis, and satellite cell proliferation. In bone tissue, RAD-140 appears to stimulate osteoblast activity and increase bone mineral density in preclinical models, though the magnitude of these effects is smaller than in muscle. Importantly, RAD-140 does not undergo 5-alpha-reductase conversion to a more potent metabolite (unlike testosterone converting to dihydrotestosterone), which contributes to its reduced effects on sebaceous glands, hair follicles, and prostate tissue.

Twenty-Eight Days of Rodent Data, One Small Human Safety Trial: What the Evidence Actually Covers

The primary evidence base for RAD-140 consists of preclinical animal studies and one unpublished Phase I human trial. Most published RAD-140 research comes from Radius Health's internal studies and a small number of independent investigations in castrated male rats.

In a 2011 study by Miller et al. published in Endocrinology, orally administered RAD-140 prevented the loss of levator ani muscle weight in castrated male rats—a standard model for anabolic androgenic effects. At doses of 0.1 mg/kg/day, RAD-140 maintained muscle weight comparable to testosterone propionate at 0.5 mg/kg/day, but with significantly less prostate enlargement. Prostate weight in RAD-140-treated animals remained near castrate levels, while testosterone propionate-treated animals showed prostate weights approaching intact controls. This demonstrated tissue selectivity in a direct head-to-head comparison.

A subsequent study by Jayaraman et al. (2014) in ACS Medicinal Chemistry Letters reported that RAD-140 increased lean body mass and reduced fat mass in female rats at oral doses of 0.1–0.75 mg/kg/day over 28 days. The compound also increased bone mineral density in ovariectomized rats, suggesting potential protective effects against osteoporosis. Importantly, these effects occurred without significant changes in uterine weight, indicating that RAD-140 did not behave as an estrogen receptor agonist.

Human data is sparse. Radius Health conducted a Phase I dose-escalation trial evaluating RAD-140 in healthy male volunteers at doses ranging from 0.01 to 0.1 mg/kg. This study, presented at the Endocrine Society meeting in 2010, reported that RAD-140 was well-tolerated with no dose-limiting toxicities, but detailed results were never published in a peer-reviewed journal. No Phase II efficacy trials have been completed or published as of 2026.

No controlled human studies have evaluated RAD-140 for muscle hypertrophy, strength gains, or body composition changes. The anabolic effects reported in online communities are based on anecdotal self-experimentation, not clinical trials. Additionally, no long-term safety data exist in any species beyond 28 days of exposure.

Mechanistic studies in cell culture have shown that RAD-140 activates the androgen receptor in C2C12 myoblasts (a mouse muscle cell line), promoting differentiation and myotube formation. These in vitro effects occur at nanomolar concentrations, consistent with RAD-140's high receptor binding affinity. However, cell culture results do not predict tissue-specific effects or long-term safety in whole organisms.

Dosing Ranges, Pharmacokinetics, and Practical Research Parameters From Published Literature

Published rodent studies used RAD-140 at oral doses between 0.1 and 0.75 mg/kg/day. In a 70 kg human, direct allometric scaling from rat to human (dividing the rat dose by a factor of approximately 6.2) suggests an equivalent dose range of roughly 1.1–8.4 mg/day. However, allometric scaling is an imperfect approximation, and the Phase I human trial tested doses up to 0.1 mg/kg (approximately 7 mg for a 70 kg individual), though specific pharmacokinetic parameters were not published.

RAD-140 is orally bioavailable, with absorption occurring in the gastrointestinal tract. The compound's estimated half-life in humans is 15–20 hours based on preclinical pharmacokinetic modeling, though this has not been confirmed in published human studies. This half-life supports once-daily oral dosing, which is typical in research protocols.

Stability data for RAD-140 are limited. The compound is typically supplied as a powder and reconstituted in a solvent such as polyethylene glycol 400 (PEG-400), dimethyl sulfoxide (DMSO), or a PEG-ethanol mixture. Anecdotal reports suggest RAD-140 powder is stable for at least two years when stored at -20°C in a sealed container protected from light and moisture. Once reconstituted, stability is shorter—likely weeks to a few months at 4°C, though formal stability studies are not publicly available.

No published drug-drug interaction studies exist for RAD-140. Theoretically, compounds that induce or inhibit cytochrome P450 enzymes could alter RAD-140 metabolism, but the specific enzymes involved in RAD-140 clearance have not been characterized in peer-reviewed research. Concurrent use with other androgen receptor ligands (including anabolic steroids or other SARMs like MK-677) has not been studied in controlled settings.

RAD-140 suppresses endogenous testosterone production in males through negative feedback on the hypothalamic-pituitary-gonadal axis. In the Miller et al. study, castrated rats did not produce endogenous testosterone, so suppression was not measurable. However, in intact male animals and humans, any exogenous androgen receptor agonist—including RAD-140—reduces luteinizing hormone secretion, leading to decreased testicular testosterone synthesis. The degree and duration of suppression in humans remains poorly characterized because no controlled studies have measured hormonal recovery timelines after RAD-140 discontinuation.

FAQ

Q: Does RAD-140 require post-cycle therapy in research models?

In intact male animals and humans, RAD-140 suppresses endogenous testosterone production through negative feedback on luteinizing hormone secretion. Discontinuation typically allows the hypothalamic-pituitary-gonadal axis to recover, but the timeline is unstudied in humans. Anecdotal reports suggest partial recovery within weeks, though individual variability is high and no controlled data exist.

Q: What differentiates RAD-140's mechanism from testosterone at the receptor level?

Both bind the androgen receptor, but RAD-140 induces a slightly different receptor conformation, leading to tissue-specific differences in cofactor recruitment. This results in strong transcriptional activation in muscle and bone but weaker activity in prostate and sebaceous tissue. Testosterone, by contrast, activates the receptor more uniformly across tissues and converts to dihydrotestosterone via 5-alpha-reductase, amplifying effects in androgen-sensitive tissues.

Q: Why haven't RAD-140 trials advanced beyond Phase I?

Publicly available reasons are not documented. Radius Health has not published Phase II results or announced further development for muscle wasting or other indications. Possible explanations include insufficient efficacy signals in early testing, strategic reprioritization, or safety concerns, but no official statements clarify the development status as of 2026.

Q: Can RAD-140 increase bone mineral density in humans?

In ovariectomized rats, RAD-140 increased bone mineral density at doses of 0.1–0.75 mg/kg/day. No human trials have tested RAD-140 for bone density outcomes. Extrapolation from rodent models to human skeletal physiology is uncertain, and bone turnover timelines differ significantly between species.

Q: What evidence exists for RAD-140's effects on body composition?

In female rats, RAD-140 increased lean mass and decreased fat mass over 28 days. No controlled human trials have measured body composition changes. Anecdotal reports from self-experimenters describe lean mass gains and fat loss, but these lack control groups, blinding, or objective measurement methods, making them unsuitable for drawing conclusions.

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RAD-140 is not approved for medical use and is not intended to diagnose, treat, cure, or prevent any disease. The information provided here is for educational and research purposes only and does not constitute medical advice.