Different SARMs Research and Its Testing

SARMs are under continuous development as promising alternatives to anabolic-androgenic steroids (AAS). SARMs screen tissue-selective androgen activation, unlike AAS which binds with androgens throughout the human body adversely affecting untargeted tissues such as the prostate, heart, or other organs (source). This tissue-selectivity creates SARMs ideal for the improvement of musculoskeletal physical function, as well as bone health, and proceeds to drive clinical study and testing of these regenerative and restorative drugs.

MK-2866 (Ostarine, Enobosarm)

MK-2866, typically known as Ostarine, Is an investigational SARM currently developed by pharmaceutical firm GTx Incorporated for the treatment of muscle wasting and osteoporosis. Ostarine can be bought online and is currently the most researched SARM in existence.

• Clinical Trials

“Selective androgen receptor modulators (SARMs) differentially bind to androgen receptors based on every SARM's compound structure. As a result, SARMs result in anabolic cellular activity whilst avoiding many of the side effects of currently available anabolic steroids. SARMs have been studied in treating breast cancer and cachexia and have also been utilized as performance-enhancing agents." (Source: Selective Androgen Receptor Modulators (SARMs) -- Current Knowledge and Clinical Applications).

In 2011 a 12-week double-blind, Placebo-controlled phase II clinical trial was conducted to evaluate Ostarine in 120 healthy and women. 120 subjects were randomized to Ostarine 0.1, 0.3, 1.0, or 3.0 mg versus placebo over 3 months. At the end of the trial, substantial growth in total lean body mass and progress in measures of physical function were quantified in the 3-mg group (source: The selective androgen receptor modulator GTx-024 (enobosarm) enhances lean body mass and physical function in healthy older men and postmenopausal women).

Finally, in two separate Phase III trials of Ostarine, 325 patients with stage III or IV NSCLC and muscle wasting were randomized to Ostarine 3 mg versus placebo for 3 months, with primary endpoints including total lean body mass and improvement in physical function. Again, the researchers found substantial growth in overall lean body mass in comparison to placebo (GTx Announces Late Breaker Presentation on Results from the Two-Phase 3 POWER Trials of Enobosarm).

LGD-4033 (Ligandrol)

LGD-4033, typically referred to as Ligandrol, is an investigational SARM discovered by Ligand Pharmaceuticals and now under development by Viking Therapeutics for treating conditions like muscle wasting and osteoporosis.

• Clinical Trials

Researchers evaluated the safety of Ligandrol in a Phrase I trial that involved 76 healthy men (21–50 years). These men were randomized to placebo or 0.1, 0.3, or 1.0 mg LGD-4033 per day for 21 days. The researchers concluded by saying Ligandrol was well tolerated (The Safety, Pharmacokinetics, and Effects of LGD-4033, a Novel Nonsteroidal Cosmetic, Selective Androgen Receptor Modulator, in Healthy Young Men).

"LGD-4033 administration was associated with a dose-dependent reduction of testosterone, sex hormone-binding globulin, high-density lipoprotein cholesterol, and triglyceride levels. Follicle-stimulating hormone and free testosterone revealed a significant reduction at a 1.0-mg dose just. Lean body mass raised dose-dependently, but fat mass didn't change significantly. Hormone levels and lipids returned to baseline after therapy discontinuation," the researchers noted.

In 2017, Viking Therapeutics completed enrollment in the Phase II trial of Ligandrol in patients recovering from a hip fracture. Viking Therapeutics plans to administer once-daily doses of 0.5 mg, 1.0 mg, 2.0 mg, or placebo for 12 weeks to 108 patients to study the consequences of Ligandrol on lean body mass, functional performance, and quality-of-life, among other things (source).

MK-677 (Ibutamoren)

MK-677, typically known as Ibutamoren, a potent non-peptide agonist of the ghrelin receptor along with also a growth hormone secretagogue. MK 677 mimics the growth hormone (GH)-stimulating action of the adrenal hormone ghrelin, which regulates appetite and plays a significant role in regulating the distribution and speed of usage of energy.

• Clinical Trials

The effects of MK-677 on the growth hormone (GH)-insulin-like growth factor I axis were studied during a stage I and II trial involving 32 healthy subjects. The subjects received placebo or two, 10, or 25 mg MK-677, orally, once daily for 2 separate study periods of 14 and 28 days. After daily treatment of older individuals with oral MK-677 to get up to 4 months at a dose of 25 mg/day restored serum IGF-I concentrations to those of adults (Stimulation of the growth hormone (GH)-insulin-like growth factor I axis by daily oral administration of a GH secretagogue (MK-677) in healthy elderly subjects).

During a 1999 trial whose goal was to determine the effect of chronic administration MK-677 on serum IGF-I and markers of bone turnover in 187 elderly adults, 30 subjects received either placebo for 4 weeks or 25 mg of MK-677 daily for two weeks followed by 50 mg daily for fourteen days. The researchers noted that the ability of MK-677 to significantly increase serum IGF-I levels stimulates bone turnover in elderly subjects (Oral administration of the growth hormone secretagogue MK-677 increases markers of bone turnover in healthy and functionally impaired elderly adults).

YK-11

YK-11 is a myostatin inhibitor, in the form of a synthetic SARM, with significant anabolic activity demonstrated during an in vitro study (Selective androgen receptor modulator, YK11, regulates myogenic differentiation of C2C12 myoblasts by follistatin expression). 

Accompanied by follistatin, YK11 causes increased production of myogenin, myogenic factor 5 (Myf5), and myogenic differentiation factor (MyoD). This myogenin cause gains in differentiated muscle cells at a greater speed than DHT or Testosterone alone.

Because in vitro studies have been performed with microorganisms, cells, or biological molecules out of their normal biological circumstance, they might not fully or accurately predict the effects on a complete organism.

RAD-140 (Testalone)

RAD-140 typically referred to as Testalone, is a potent, orally highly-bioavailable, nonsteroidal SARM currently under development by Radius Health for treating conditions such as muscle wasting and breast cancer.

• Clinical Trials

Several studies have been conducted showing impressive and muscle-selective anabolic activity. A 2010 study with monkeys produced lean muscle mass weight gain of greater than 10% in just 28 days at a dose of merely 0.1 mg/kg, in addition to a significant decrease in fat tissue. More recently, RAD-140's inhibiting effect on the growth of the androgen/estrogen receptor has found it to be a very promising drug in the battle against breast cancer. A fascinating study in 2014 revealed RAD-140 may offer neuroprotective actions and resilience to bronchial disorders, which might signal an ability to assist in the prevention and reduction of Alzheimer's and related diseases.

GW-501516 (Cardarine)

GW-501516 typically referred to as Cardarine, is a PPARδ receptor agonist. It was invented in a collaboration between Ligand Pharmaceuticals and GlaxoSmithKline in the 1990s as a drug candidate for metabolic diseases and cardiovascular diseases.

• Clinical Trials

A 2012 study showed this SARM effective at helping with repairing liver damage. During animal testing, Cardarine was discovered to cause cancer cells to develop if given to rats at daily ultra-doses of 3 mg per kg of body weight (source). A few clinical trials have also been performed on cardarine and its effects on fat metabolism. Despite pessimistic findings in rodents, "no substantial adverse effects were reported in any of the individual studies, which might reflect the considerably lower doses handled (up to 10 mg/day) for much shorter periods (around 12 weeks)".

S-4 (Andarine)

S-4, typically known as Andarine, is an investigational SARM developed by GTx Incorporated for the treatment of conditions like muscle wasting, osteoporosis, and benign prostatic hypertrophy. Although Andarine is proven to have a similar chemical structure to Ostarine (the compound structure of Ostarine has never been publicly revealed), the two medications are not the same.

• Clinical Trials

In various trials, S-4 treatment was shown to reduce body fat and improve body strength. GTx completed phase I research on both Andarine and Ostarine and discovered both drugs equally safe. According to Nonsteroidal Selective Androgen Receptor Modulators (SARMs): Dissociating the Anabolic and Androgenic Activities of the Androgen Receptor for Therapeutic Benefit, "Ostarine was chosen for advanced clinical development based on corporate strategy," while testing of Andarine was ceased.

SARMs Legal Status

In the United States and several other countries, all SARMs like MK 677, RAD-140, LGD 4033, and many more are currently in the testing and research phases for various physical ailments and health conditions. Since investigational new drugs, SARMs are sold online like SARMs Pharm, but they can't be lawfully advertised and labeled as dietary supplements -- a significant distinction.

In 2017, the FDA’s Center for Drug Evaluation and Research put out a warning regarding the use of SARMs in Body-building goods: "We are extremely concerned about unscrupulous companies marketing body-building products with potentially harmful ingredients. Body-building products that contain selective androgen receptor modulators, or SARMs, have not been accepted by the FDA and are associated with serious safety concerns, including the potential to raise the risk of heart attack or stroke and life-threatening reactions like liver damage."