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LGD-4033 (Ligandrol) Sarm

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Description

LGD-4033 (Ligandrol) description

LGD-4033 (often also called as Ligandrol) is a oral, nonsteroidal and potent selective androgen receptor modulator (SARM). It was developed to increase anabolic activity and reduce muscle wasting in people with severe diseases associated with catabolic conditions and critical loss of muscle mass. In clinical trials, LGD-4033 has shown significant anabolic activity in muscles and antiresorptive and anabolic activity in bones, along with a high selectivity to act in these tissues (where appropriate and desirable) and minimally in other tissues and organs, where undesirable. LGD-4033 binds to androgen receptor with high affinity (Ki of ∼1 nM) and selectivity, has chemical formula C14H12F6N2O, molecular mass 338.253 g·mol−1, prolonged elimination half-life 24–36 hours and linear pharmacokinetics.

LGD-4033 (ligandrol) chemical structure
LGD-4033 (Ligandrol) chemical structure

LGD-4033 development and history

SARM LGD-4033 (Ligandrol) was discovered by Ligand Pharmaceuticals and is currently being developed (under the new designation VK5211) by Viking Therapeutics, which currently does not manufacture any pharmaceutical products but develops several products for the treatment of metabolic and endocrine disorders. Viking Therapeutics assumed the largest expense in 2014 from cited Research and Development costs ($21.2M), which may be related to purchase of required equipment and facilities to develop the drug candidates licensed by Ligand Pharmaceuticals in that year, including LGD-4033. Another promising drug candidate, VK2809, is expected to drive a major shift in the market cap of Viking Therapeutics and its share of the market for TRβ agonists. In the United States, LGD-4033 is currently an investigational compound.

Ligandrol, research and possible clinical use in the future

SARM LGD-4033 is a nonsteroidal selective androgen receptor modulator that is expected to deliver the therapeutic benefits of testosterone with improved safety, tolerability and patient acceptance due to tissue-selective mechanisms of action and oral routes of administration. The research carried out indicates that LGD-4033 seems to be promising candidate for treatment of serious diseases associated with muscle wasting in future, however, the long-term effects of LGD-4033 are not fully known and investigated so far, and further research is still needed.

LGD-4033 and Phase 1 & 2 clinical trials

Administration of LGD-4033 to cynomolgus monkeys at daily doses varying from 0 to 75 mg/kg over 13 weeks demonstrated significant body weight gain in both males and females. After 48 days, the 75 mg/kg dose testing was halted due to toxicity concerns, but this did not negatively impact development as the dose is significantly higher than those being utilized in the Phase 2 clinical trial.

First clinical study in a Phase 1 was the first study in humans of LGD-4033, and evaluated the safety, tolerability and pharmacokinetic profiles of the molecule in a single escalating dose, double blind, placebo-controlled study in 48 healthy volunteers. LGD-4033 was well tolerated by healthy male volunteers after single oral doses up to 22 mg. No serious adverse events (SAE) or clinically significant dose-related adverse events were reported. Systemic exposure of LGD-4033 increased proportionally with the dose level after a single oral dose. Sustained systemic exposure was observed with appreciable plasma levels of LGD-4033 detectable a week post-dose. LGD-4033’s half-life was consistent with a regimen of once-daily oral dosing.

In another Phase 1 clinical study with 76 adult males who receiving escalating low doses of 0.1, 0.3 and 1 mg of LGD-4033 per day, a dose-dependent increase in muscle mass was observed, with no significant adverse effects for 21 days, and a dose of 1 mg of Ligandrol daily was enough to increase lean muscle mass by nearly 3 pounds. However, lower doses had no effect.

The Phase 2 clinical trial, initiated on 3 November 2016, consists of 120 patients recovering from hip fracture surgery. The randomized study participants will receive either a placebo or varying dose sizes of LGD-4033 over a period of 12 weeks, with improved lean body mass as the primary endpoint. Other endpoints include satisfactory results in terms of quality of life, safety, and pharmacokinetics.

LGD-4033 strongly stimulates the growth of muscle mass

The results of clinical trials conducted by the Endocrinology section of the Boston Medical Center also indicate that LGD-4033 can significantly help in increasing muscle mass and muscle strength in severe diseases associated with muscle wasting and without significant side effects (which may be caused by treatment of these diseases with androgenic drugs – steroids). Similarly, another study conducted in January 2013 confirmed that Ligandrol can help increase muscle mass in muscle tissue and its use was well tolerated by test subjects.

LGD-4033 and bodybuilding

Like anabolic androgenic steroids (AAS), LGD-4033 also has a very strong ability to stimulate significant muscle gains. However, unlike AAS, LGD-4033 as a Selective androgen receptor modulator (SARM), is able to provide its strongly anabolic effects and bind to androgen receptors in the body only where desired, in muscles and bones (its action is selectively targeted just to these tissue). And conversely, it does not act (or minimally compared to AAS) in tissues and organs where this is undesirable and where it could cause serious side effects (prostate, liver, sebaceous glands, etc).

So when we summarize it: LGD-4033 (Ligandrol) has a very strong anabolic activity that makes it possible to help bodybuilders and athletes achieve muscle gains fully comparable to those that can be achieved using the most effective “bulking” anabolic steroids, but without most of the dangerous and unpleasant side effects that such steroids cause. Thus, Ligandol is a great full-fledged alternative for them to the most effective anabolic steroids aimed at muscle gains, while being much safer, less harmful and less risky than using steroids.

This is why the LGD-4033 is so popular and well-known among bodybuilders and strength athletes. However, it should be emphasized here that the use of LGD-4033 as a nutritional supplement or stimulant of sports performance is illegal in many countries. It is an experimental substance whose research is still ongoing, its long-term effects are not fully known and investigated so far, and further research is still needed. Please also keep in mind that the LGD-4033, like all our other products, is sold solely for scientific and research clinical use only.

Ligandrol and doping

The World Anti-Doping Agency (WADA) banned all SARMs (including Ligandrol) as early as 2008. Since then, there have been several notable cases where professional athletes have been positive tested for LGD-4033:

In 2015, the quarterback of the Florida Gators, Will Grier, was suspended for testing positive for Ligandrol, a claim that the University of Florida denies. In 2017, Joakim Noah was banned for twenty games by the NBA for testing positive for LGD-4033. In 2019, Australian swimmer Shayna Jack also tested positive for Ligandrol; she denies knowingly taking the substance. In August 2019, it came to light that Canadian sprint canoeist Laurence Vincent Lapointe tested positive for Ligandrol; the athlete denies knowingly taking a forbidden substance. In January 2020, Chilean ATP tennis singles competitor Nicolás Jarry tested positive for both Ligandrol and Stanozolol.

However, despite bans and the negative media presentation, bodybuilders and athletes at many internet forums and discussions argue that the LGD 4033 is the most effective SARM on the market and the only functional and simultaneously a much safer way to achieve massive muscle gain without the use of anabolic steroids.

Scientifically investigated possible benefits of LGD-4033

    • Significant and selective anabolic activity in muscles and bones, without strong androgenic undesirable effects and negative effects in other organs
    • Promising candidate for the treatment of serious diseases associated with muscle wasting
    • Promising candidate for the treatment of osteoporosis and fractures
    • Very effectively helps build lean muscle mass
    • Has strong anti-catabolic effects and ability to maintain muscle mass even with reduced caloric intake
    • Increases bone density and helps prevent bone loss

Advantages of LGD-4033 over Anabolic-Androgenic Steroids

    • SARM LGD-4033 is highly selective and primarily aimed at acting in muscles and bones. Due to this selectivity, unlike anabolic steroids, it does not cause strong androgenic side effects and negative effects on other organs
    • LGD-4033 has anabolic activity fully comparable to anabolic steroids, is able to help achieve muscle mass growth in the similar results, but without many of the negative effects and health risks that arise from the use of anabolic steroids:
        • LGD-4033 does not interact with enzymes of CYP19 aromatase or 5α-reductase (LGD-4033 does not convert on Estrogens or Dihydrotestosterone (DHT))
        • LGD-4033 does not cause Gynecomastia (abnormal development of mammary glands in men causing breast enlargement)
        • LGD-4033 does not cause significant retention of water and salts in the body
        • LGD-4033 does not cause increased Cortisol and Estrogen production
        • LGD-4033 does not present a heavy load and damage to the Liver
        • LGD-4033 does not cause prostate enlargement
        • LGD-4033 does not cause kidney disease
        • LGD-4033 does not cause acne and oily skin
        • LGD-4033 does not cause hair loss and baldness
        • LGD-4033 does not cause swollen face
        • LGD-4033 does not cause excess facial or body hair (hirsutism)
        • LGD-4033 does not cause sudden changes in mood and behavior
        • LGD-4033 does not cause irritability, nervousness, depression, restlessness
        • LGD-4033 does not cause aggression, explosiveness and psychological problems
        • LGD-4033 is highly effective when administered orally (no injections required)

LGD-4033 possible side-effects

    • LGD-4033 suppresses the production and reduces the levels of natural Testosterone in the body
    • After discontinuation, therapy is required in many cases to restore the natural production of testosterone
    • LGD-4033 may increase the risk of heart attack and stroke (in the elderly)
    • LGD-4033 may have adverse effects on blood lipid levels
    • LGD-4033 may decrease libido and potency

LGD-4033 (Ligandrol) FAQ

What is LGD-4033 (Ligandrol)?

LGD-4033 (Ligandrol) is a oral, nonsteroidal and potent selective androgen receptor modulator (SARM), expected to deliver the therapeutic benefits of testosterone with improved safety, tolerability and patient acceptance due to tissue-selective mechanisms of action and oral routes of administration.

What does LGD-4033 do?

LGD-4033 binds to androgen receptor with high affinity (Ki of ∼1 nM) and selectivity in muscle and bone tissues. It has strong anabolic effects on building new muscle mass, and strong anti-catabolic effects and ability to maintain muscle mass even with reduced caloric intake.

What is Ligandrol used for?

LGD-4033 is a selective androgen receptor modulator (SARM), that is currently being investigated as a pharmaceutical treatment for muscle wasting and weakness associated with aging.

Does LGD-4033 Ligandrol build muscle?

The results of clinical trials conducted confirmed that LGD-4033 can significantly help in increasing muscle mass, it has strong anabolic properties, and moreover, it act selectively only in tissues where it is required, in the muscles and bones.

Is the LGD-4033 the strongest SARM for building muscle mass?

Bodybuilders and athletes at many internet forums and discussions argue that the LGD 4033 is the most effective SARM on the market and the only functional and simultaneously a much safer way to achieve massive muscle gain without the use of anabolic steroids.

Does LGD-4033 Ligandrol have strong side effects?

In clinical studies performed LGD-4033 appeared to be safe and well tolerated. It is highly selective and binds to androgen receptors in the body only where desired, in muscles and bones. Due to this selectivity, also its possible side effects are many times milder, less numerous and less dangerous compared to anabolic steroids.

Does LGD-4033 cause gynecomastia?

LGD-4033 does not cause Gynecomastia (abnormal development of mammary glands in men causing breast enlargement), because it does not interact with enzymes of CYP19 aromatase.

Is LGD-4033 dangerous for the prostate?

LGD-4033 is highly selective for action only in muscle and bone, does not interact with 5α-reductase enzymes (does not convert to dihydrotestosterone), therefore, unlike anabolic steroids, it does not pose a risk to the prostate (its enlargement or cancer)

Does LGD-4033 cause increased cortisol production?

No, LGD-4033 does not affect cortisol levels and does not increase its production in the body

Is Ligandrol banned in sports?

Yes, the World Anti-Doping Agency (WADA) banned all SARMs including Ligandrol (LGD-4033) as early as 2008.

Is LGD-4033 Ligandrol use legal in USA?

Since LGD-4033 Ligandrol is still a investigational new compound, it has not yet been approved to be marketed for consumption by humans in the United States. However, it has been used experimentally by some in the bodybuilding community.

Does LGD-4033 Ligandrol lower testosterone?

LGD-4033 suppresses the production and reduces the levels of natural Testosterone in the body, but considerably less than some anabolic steroids. The effect on the reduction of testosterone production is also influenced by the size of the dose and the length of its use.

How safe is LGD 4033?

In clinical studies performed LGD-4033 was safe, had favorable pharmacokinetic profile, and increased lean body mass even during this short period without change in prostate-specific antigen. Longer randomized trials should evaluate its efficacy in improving physical function and health outcomes in select populations.

LGD-4033 dosage

While one phase 1 clinical study found that even a low dose of 1 mg LGD-4033 (Ligandrol) daily led to an increase in muscle mass, another phase 1 clinical study found that LGD-4033 was well tolerated by healthy male volunteers after single oral doses of up to 22 mg.

However, if higher doses (over 20 mg) are used, in addition to increasing the overall anabolic effect, the negative effect of LGD-4033 on suppressing endogenous testosterone production may also increase. Therefore, a dose of 10-20 mg per day could be considered optimal. Due to long half-life of LGD-4033, 1 dose per day is sufficient.

We emphasize that LGD-4033 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 LGD-4033, like all our other products, is sold solely for scientific and research clinical use.

Additional information

Synonyms

Ligandrol, VK5211, VK-5211

CAS Number

1165910-22-4

Molecular formula

C14H12F6N2O

Molecular weight

338.253 g·mol−1

Restrictions

Sold for the scientific research use only

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