RAD-140 (testolone) is a non-steroidal selective androgen receptor modulator (SARM). SARMS have been under investigation since the 1990s and in the last few years have exploded onto the bodybuilding scene, for their anabolic potential, without the severity of induced side effects compared to their steroid related counterparts. We’re going to discuss the research behind RAD-140, the benefits, uses, and potential side effects.
What Is RAD-140 (testolone), EP0062
RAD-140 is an investigational non-steroidal selective androgen receptor modulator (SARMS). Developed by Radius Health, Inc, for potential therapeutic use in androgen replacement therapy, it was licensed to Ellipses Pharmaceuticals in 2020, for its potential therapeutic use in the treatment of breast cancer and is now referred as EP0062/vosilasarm.
RAD-140 whose synthesis was first described in 2011, from in-vitro studies, showed osteoblast differentiation potential in C2C12, neuroprotective properties in primary rat neurons as well as androgen receptor (AR) agonistic effects and growth suppression of AR+ breast cancer cells.
SARMS are currently investigational drugs being developed in an attempt to overcome the pharmacologic and pharmacokinetic limitations of steroidal androgen receptor agonists (i.e., testosterone and DHT), which have known associations with liver and heart disease [R].
SARMS have been investigated for several indications such as cachexia (muscle wasting), osteoporosis (bone loss), stress urinary incontinence, erectile dysfunction, symptomatic benign prostatic hyperplasia, Alzheimer’s disease, muscular dystrophy, and breast cancer [R].
Selective androgen receptor modulators comprise compounds that bind as ligands to the androgen receptor and possess tissue-selective activities. Ideally, they show agonistic properties in anabolic target tissues (muscle, and bone), while inducing antagonistic or only weak agonistic effects in reproductive organs (prostate) [R].
How Does RAD-140 (testolone) Work
RAD-140 is a relatively new compound, with Phase 1 study results completed just in 2020. Phase 1 clinical trials are the first step in human clinical trials to establish safety, efficacy, and dose tolerability, in order to proceed with further investigation for indicated therapeutic use.
In addition to high tissue-selectivity of androgen receptors in muscle and bone, preclinical animal data shows that RAD-140 has neuroprotective effects. The natural decline in testosterone levels is normal of the aging process, with increased risk in androgen responsive tissues. These tissues also include the brain. Testosterone replacement therapy (TRT) has the risk of inducing changes in tissues other than muscle and bone and accelerating the progression of cancer. To overcome these limitations, research is currently on going with SARMS as a potential alternative.
Preclinical data shows that RAD-140 was as effective as testosterone in reducing cell death induced by apoptotic insults. Mechanistically, RAD140 neuroprotection was dependent upon MAPK signaling, as evidenced by elevation of ERK phosphorylation and inhibition of protection by the MAPK kinase inhibitor U0126 [R].
These findings show initial preclinical efficacy of a SARM in neuroprotective actions relevant to Alzheimer’s disease and other age-related neurodegenerative disease states.
Animal studies reveal that RAD140 appears to be a potent and complete androgen agonist on the levator ani muscle but a weaker, partial antagonist on the seminal vesicle and possibly the prostate.
RAD-140 (testolone) Benefits
Increases Lean Muscle Mass
Preclinical animal studies shows that RAD-140 has high dose-dependent selectivity on muscle mass. Administered animal models found that RAD-140 increased muscle mass, yet, had no effect on or stimulation of the prostate at 0.1mg/kg. RAD140 demonstrated no stimulation of the prostate above the intact animal control level until the highest dose tested, 30 mg/kg.
RAD-140 like other SARMS, has a high binding affinity to androgen receptors, with high oral bioavailability. RAD140 demonstrated muscle efficacy similar to testosterone propionate at 0.5 mg/kg, but a dose of 30 mg/kg of RAD140 was required to approximate the prostate efficacy of 0.5 mg/kg TP.
In just 28 days of dosing at 0.1 mg/kg, a greater gain of 10% in muscle mass and weight occurred with a similar effect observed at the 1.0 mg/kg dosing group.
Preclinical research has shown that androgen receptor activation exerts potent antitumor activity across a number of ER+/AR+ breast tumors, including those resistant to standard-of-care endocrine therapy and CDK4/6 inhibitors [R].
Phase 1 study of RAD-140 safety, tolerability, maximum tolerated dose (MTD), pharmacokinetic (PK) profile, and antitumor activity of RAD140, was exhibited and investigated with postmenopausal women with ER+/HER2- metastatic breast cancer (mBC).
21 patients were enrolled, and dosed at levels of 50, 100, and 150mg once daily. Most frequent treatment-emergent adverse events (TEAEs) were elevated AST (59.1%), ALT (45.5%), and total blood bilirubin (27.3%), and vomiting, dehydration, and decreased appetite and weight (27.3% each).
SARMS have several etiologies as agonists of androgen receptors. Mechanistically, RAD-140 showed agonist activation of AR and alters the genomic distribution of estrogen receptors and essential co-activators resulting in repression of estrogen receptor-regulated cell cycle genes and up-regulation of androgen receptor target genes, including known tumor suppressors.
Future, phase 2 studies will investigate safety and efficacy, as well as establish a threshold for patient selection as well as efficacy combined with established standard of care therapies [R].
RAD-140, (testolone), EP0062 Side Effects
Preclinical and Phase 1 data shows that RAD-140, EP0062 is well tolerated and safe from 0.1mg to 150mg per day, at 24 weeks.
However, SARMS do exhibit several side effects. Without long-term efficacy and toxicity studies, it is impossible to know the long-term detriment, these compounds can create [R].
Yet due to the trial length of RAD-140, 24 weeks, is a longer clinical evaluation than most SARMS.
Studies show that RAD-140, like other SARMS does suppress high-density lipoproteins, (HDL), LDL and triglycerides in a dose-dependent manner [R]. Negative effects are also notorious and associated with therapeutic application of all anabolic steroids and non-steroidal anabolics.
SARMs have shown to suppress luteinizing hormone (LH) and follicle stimulating hormone (FSH) through the hypothalamus-pituitary-testis axis, thus decreasing testosterone in a dose-dependent manner [R].
Studies also show, RAD-140 does reduce other hormones specifically sex hormone-binding globulin (SHBG). Commonly reported symptoms and findings for all SARMs were headaches, dry mouth, and upper respiratory infections (URIs), constipation, dyspepsia, and nausea.
Moreover, RAD-140 does not aromatize into Estrogen, yet it can still cause a systemic increase or decrease in Estrogen levels.
RAD0140, like other SARMS, suppresses natural Testosterone levels, which can result in an disparaging balance between Testosterone and Estrogen levels in the body.
This can result in symptoms such as
- Low Libido
- Depressive Mood State
- High Blood Pressure
- Change in testicular size
Pharmacokinetics studies and Phase 1 clinical trials show that the average terminal half-life of RAD-140 is 44 hours and was rapidly absorbed and completely bioavailable [R].
Therefore, post cycle therapy is recommended to be started immediately after application has been concluded.
Any anabolic agent, SARMS or not, increase androgen activity. While RAD-140 is selective for muscle and bone relative to androgen modulation there is still potential for androgen related side effects.
Anabolic agents are well known to cause liver damage which may manifest with elevated liver enzymes. Selective androgen receptor modulators (SARMs) have been heavily marketed as alternatives to androgenic anabolic steroids (AASs) for muscle gain and physical performance because of their perceived superior side-effect profile.
RAD-140 does show changes in AST or ALT levels in human trials at doses much higher than those shown for efficacy, ranging between 01mg/kg of body weight to 1.0mg/kg of body weight. Despite the rather dramatic increases in body weight over such a short time, there was no elevation of liver enzyme transaminase levels in any animal at any dose >2 fold over its baseline value. Given the well-established relationship between oral androgen use and liver stress indicators, we were quite pleased that at a dose 10-fold greater than the fully effective dose we saw minimal liver enzyme elevations [R].
Doses ranging between 50-150mg per day, can result in elevated AST and ALT levels.
At therapeutic dosages, there appears to be a low risk associated with use and liver damage. However, it should be noted, that any anabolic modulator may have some degree of liver toxicity with ergogenic dosages.
With doses higher than 10mg per day, it is possible, that RAD-140, will exhibit some degree of liver toxicity, However, at therapeutic dosages, there appears to be a strong safety profile and the data suggests a complete absence of liver toxicity.
Is RAD-140, EP0062 Legal
RAD-140 is classified as experimental and used for research purposes.
RAD-140, now EP0062 is classified as an investigational new drug by the FDA, meaning that it is still being studied and has not been approved for human use. As such, it is illegal to sell or distribute EP0062 in the U.S. for any purpose other than FDA-approved clinical trials.
Thus, it is legal to sell and buy SARMs that are marketed for research purposes, which commonly occurs online. However, it is illegal to sell and buy those that are packaged in capsules for human consumption and/or labeled as dietary supplements. Furthermore, SARMS cannot be marketed to the public as dietary supplements and claims regarding their benefits cannot be made.
SARMs were banned by the World Anti-Doping Agency in January 2008, despite no drugs from this class yet being in clinical use, and blood tests for all known SARMs have been developed.
RAD-140, EP0062 is still under investigation, for metastatic breast cancer indications.
Swolverine is no way supports or condones the use of illegal or nefarious substances or compounds. This article is for informational purposes only.
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