RAD140

Description

RAD140 (also known as Testolone) is an oral nonsteroidal selective androgen receptor modulator (SARM) that cannot be converted to estrogen by aromatase. It has been demonstrated that RAD140 has high AR affinity and target selectivity, showing marked tissue-selective AR agonist activity comparable to natural androgens in breast cancer cells, while lacking agonist activity in prostate cancer cells.
We have recently reported anti-tumor activity of RAD140 in multiple in vivo and in vitro models of AR/ER+ breast cancer as a single agent and in combination with inhibitors of CDK4/6 and mTOR.
Pharmacodynamic investigation indicates RAD140 acted as an AR agonist in breast cancer cells while suppressing ER signaling and reduced ESR1 mRNA expression.

RAD140 exhibited anti-tumor activity in patient-derived xenograft (PDX) models of AR/ER+ breast cancer, as single agent and in combination with inhibitors of CDK4/6 or mTOR
RAD140 inhibited ER signaling and ESR1 mRNA level in the HBCx-22 PDX model.

The Uses of RAD140

RAD140 is a potent, orally bio-available, and non-steroidal selective androgen receptor modulator (SARM) for the treatment of conditions such as muscle wasting and breast cancer.

Benefits

Significant and selective anabolic effect on muscles and bones, without strong androgenic adverse effects on other organs
Has strong neuroprotective effects, may be effective in preventing Alzheimer’s disease and related neurodegenerative disorders
Has the potential to fight breast cancer
Can help treat serious diseases associated with muscle loss
Can help protect brain cells and their proper functions
May help in the treatment of osteoporosis
Helps build and maintain muscle mass
May help reduce excess fat

Biological Activity

RAD140 is an orally bioavailable, nonsteroidal selective androgen receptor modulator (SARM) that binds to the androgen receptor with a Ki value of 7nM. At 0.03-0.3mg/kg, it has been shown to stimulate muscle weight increase without affecting prostate or seminal vesicle in castrated male rats. At 0.3-1 mg/kg, RAD140 demonstrates partial antagonist activity in seminal vesicle and prostate.

Side Effects

In animal studies, RAD 140 has shown to be safer than testosterone replacement therapy, when administered to rats. This is impressive, given the general positive safety profile of testosterone, hence its FDA-approved status.
However, in humans there appears to be a different trend, with RAD 140 demonstrating harsher side effects.
Suppressed levels of natural Testosterone
Anxiety, depression
Nausea and vomiting
Possible liver toxicity
Abnormal body hair growth in women
Excessive hair loss in men (which stops after the end of RAD140 treatment)
The long-term effects of RAD140 are unknown

Synthesis

The synthesis of RAD140 is shown in Scheme 1.We relied on an expeditious, ipso-fluorine substitution of the left-hand side precursor, piece 8, with d-threonine in the presence of K2CO3 in DMSO to give the desired product 9 in workable yields (typically >50%). The d-Thr adduct 9 was coupled with 4-cyanobenzohydrazide under standard coupling conditions using EDCI and HOBt. The resultant product 10 was silylated with TBDMS-Cl, subjected to dehydrative cyclization conditions in the presence of TPP/I2, and then desilyated for the final step.Overall, this has proven to be a reliable and efficient synthesis using a fairly inexpensive, albeit nonproteinogenic amino acid as the chirality source.

Preparation and handling

RAD140 is supplied as a crystalline solid. A stock solution may be made by dissolving the RAD140 in the solvent of choice. RAD140 is soluble in organic solvents such as ethanol, DMSO, and dimethyl formamide (DMF), which should be purged with an inert gas. The solubility of RAD140 in ethanol is approximately 2 mg/ml and approximately 30 mg/ml in DMSO and DMF.
RAD140 is sparingly soluble in aqueous buffers. For maximum solubility in aqueous buffers, RAD140 should first be dissolved in ethanol and then diluted with the aqueous buffer of choice. RAD140 has a solubility of approximately 0.25 mg/ml in a 1:3 solution of ethanol:PBS (pH 7.2) using this method. We do not recommend storing the aqueous solution for more than one day.

Clinical claims and research

As no results of RAD140 clinical trials in humans are yet known, it is not yet possible to speak of frequently used or safe clinical doses of RAD140 in humans. However, a clinical study performed in young primates showed that even a low dose of 0.1 mg RAD140 per kg body weight has already led to strong anabolic effects and a significant increase in muscle mass. This suggests that RAD140 is a very potent SARM, which begins to show its strong anabolic effects already from relatively low doses.
In various bodybuilding forums and discussions on the internet, bodybuilders and users who have used (abused) RAD140 to build muscle mention 10 mg of RAD140 daily as a basic and sufficient dose to achieve significant results; and a cycle duration of 6-8 weeks. In the case of more experienced (hardcore) bodybuilders, there is talk of an optimal dose of 20 mg RAD140 per day and a cycle duration of 8 to 10 weeks. However, none of these doses are based on any scientific research.
We emphasize that RAD140 is not an approved nutritional supplement or stimulant for athletes. It is an experimental substance that is still under investigation and not all of its side effects may be known. Keep in mind that RAD140, like all our other products, is sold solely for scientific and research clinical use.

Mode of action

RAD 140 is a powerful SARM and its characteristics are much similar to those of steroids. RAD 140 has very unique working mechanism as they don't have androgenic properties, but they carry very similar anabolic properties to testosterone and other steroids. As a result, your body will get an enhanced capacity to increase the amount of protein synthesis, which is a necessary part of building muscle mass. With boosted protein synthesis, your body will work towards building more muscle with reduced recovery time. It means that you can work super hard in the gym with better and faster recovery time after workout. As RAD 140 is not an androgen, it doesn't come with the negative effects like steroids. Androgens can affect your body's natural production of testosterone in the long run and can have devastating impacts on your internal organs and fertility levels.
RAD 140 has surely has an upper hand to all other SARMs as it is pretty faster in giving better results when it comes to bulking or muscle growth. It is still under the developing stage, as researchers believe that besides preventing muscle loss, it can also be used in different treatments for health issues in the future. However, you should not really risk your health in using the bodybuilding products that haven't been approved by FDA, as RAD 140 Testolone is still under investigations and testing. Instead, you can eat clean and do workout or use legal SARMs alternatives to ensure safe bodybuilding experience.

Dosage forms

RAD140 is the most effective when used in smaller amounts. It is essential that you follow an appropriate dosage for the drug. Nothing is beneficial in excessive amounts. Since it is a SARM, it is also recommended that you use it in cycles, starting with small dosages and moving upwards.
The beginner level dosage is 5 mg every day for a week. This will allow your body to adjust and build tolerance for more as you start your daily workouts. You can later change the dosage to 10 mg every day.
The first cycle is a trial period. It should be fully completed, or the results may not turn out at optimal capacity. This first cycle should be followed for a maximum of 6 weeks. Alternatively, if you have used SARMs before, especially RAD140, then you can start with 10 mg a day for the first week and move up to 15 mg for a seven-week cycle.
More experienced consumers, who have already tried RAD140 for several cycles, can start their dosage directly at 20 mg a day for a 10-week cycle. It is essential that you discontinue the dosage if you experience any side effects at any moment in your cycle. However, you must build up your cycles if there are no side effects.
For women, the starting point for the first cycle should be 5 mg a day, which can be moved up to 10 mg a day for a cycle of 6 weeks. It is also recommended that you take the dosage in one go and not in intervals throughout the day.
It is also recommended by professionals that you do PCT since RAD140 increases the natural amount of testosterone in your body. The PCT cycle should be done for at least 4 to 6 weeks. This is done to prevent your body from any side effects. You can take 20mg of Clomid or Nolvadex every day, reducing it to 10 mg, for your PCT cycle.