Ligandrol (LGD-4033)

Overview

Ligandrol (development code LGD-4033, also VK5211, and marketed by sellers as "Anabolicum") is a nonsteroidal selective androgen receptor modulator (SARM). It is NOT a peptide — it is a synthetic small molecule (a pyrrolidinyl-benzonitrile) that binds the androgen receptor (AR). It appears on this peptide reference because it is frequently discussed and stacked alongside peptides in the fitness and "research chemical" community, not because it is one.

The "selective" in SARM refers to the theoretical goal of separating the anabolic effects of androgens in muscle and bone from the androgenic effects in tissues such as the prostate. Ligandrol was developed by Ligand Pharmaceuticals and later licensed to Viking Therapeutics, which advanced it as VK5211 into a Phase 2 trial for muscle loss after hip fracture. It has not been approved for any indication, and it is not an approved or established treatment for physique or performance enhancement.

Chemistry and structure

Ligandrol is a small-molecule androgen-receptor ligand, not an amino-acid chain.

Mechanism of action

• Androgen receptor (AR) binding. LGD-4033 is a high-affinity, nonsteroidal tissue-selective AR ligand that acts as an agonist / partial agonist, recruiting coactivators differently across tissues — the basis for the intended separation of muscle/bone anabolism from prostatic androgenic activity (weaker, partial-agonist activity in the prostate). [Human] (PMID 22459616)
• Lean-mass gain, dose-dependent. In the 21-day Phase 1 trial, dual-energy X-ray (DXA) lean body mass rose dose-dependently: about +0.2 kg (0.1 mg), +0.6 kg (0.3 mg), and +1.21 kg (1.0 mg) versus baseline, with no change in prostate-specific antigen (PSA) over the short exposure. [Human] (PMID 22459616)
• HPG-axis suppression (the central safety signal). Despite its "selective" label, LGD-4033 still suppresses the hypothalamic-pituitary-gonadal (HPG) axis: dose-dependent decreases in total testosterone, SHBG, HDL cholesterol and triglycerides; free testosterone and FSH were significantly suppressed at 1.0 mg. Suppression was measurable even at the lowest dose, and hormones/lipids returned toward baseline after discontinuation. Direct AR agonism at the hypothalamus/pituitary feeds back to reduce endogenous testosterone. [Human] (PMID 22459616)
• Functional anabolic effect in an at-risk population. In the Phase 2 VK5211 trial of adults recovering from hip fracture, once-daily dosing produced dose-dependent, placebo-adjusted increases in total lean body mass (up to ~9.1% at 2 mg) and improvements in 6-minute walk distance. [Human] (Viking Therapeutics Phase 2 top-line results, ASBMR 2018)

Research and evidence

Human evidence in context. The strongest data are a 21-day Phase 1 trial and a 12-week Phase 2 trial. Both showed dose-dependent lean-mass gains, but the exposures are short and the populations narrow. There is no Phase 3 data and no regulatory-approval efficacy/safety package for any indication. The Phase 1 trial itself documented that even a controlled, short course suppresses the HPG axis and lowers HDL — the effects most relevant to real-world, higher-dose, longer-duration misuse are not studied.

Status and regulation

• Regulatory approval: None. LGD-4033 is not approved by the FDA, the EMA, or any other regulator for any indication.
• Developer / phase history: Originated by Ligand Pharmaceuticals (Phase 1); later licensed to Viking Therapeutics, which advanced it as VK5211 into a Phase 2 trial for hip-fracture recovery. Development has not advanced past Phase 2 as of the latest available public information.
• Anti-doping: Prohibited by WADA, listed under Other Anabolic Agents (SARMs), S1.2, on the WADA Prohibited List. WADA is a sport-eligibility axis, separate from legality. (The exact sub-code wording can vary by edition; verify against the current-year WADA List.)
• Market reality: Outside clinical trials it is sold only as a "research chemical" and circulates on the black market. Such products are of unknown identity, purity, and potency.

Safety

Documented and reported signals, tagged by evidence source:

• Drug-induced liver injury (DILI) / hepatotoxicity. [Human] Post-market case reports of DILI following LGD-4033 use, including biopsy-confirmed cholestatic hepatitis in a 32-year-old man after ~2 weeks of use (Barbara et al., ACG Case Reports J 2020, PMID 32637435), and a 52-year-old man with pruritic jaundice, weight loss and elevated liver enzymes after ~3 months of high-dose use (Labban et al., Cureus 2024, PMID 39421081).
• FDA warning — liver injury including acute liver failure. [Human] The FDA warns that SARM-containing bodybuilding products are associated with life-threatening reactions including liver injury and acute liver failure requiring hospitalization, plus increased heart-attack and stroke risk; these products are unapproved drugs not reviewed by FDA for safety or effectiveness. (FDA consumer update; FDA bodybuilding-products safety communication)
• Testosterone / HPTA suppression. [Human] Even a controlled 21-day course suppressed total and free testosterone, LH, FSH and SHBG dose-dependently — even at the lowest dose (0.1 mg). Recovery toward baseline occurred after discontinuation in that controlled setting, but higher-dose / longer real-world use is unstudied. (Basaria et al., PMID 22459616)
• Adverse lipid changes. [Human] Dose-dependent reductions in HDL cholesterol and triglycerides in the Phase 1 trial — a cardiovascular-risk-relevant signal. (Basaria et al., PMID 22459616)

Product contamination and mislabeling (class-wide). [Human] A "SARM" label is not a reliable statement of contents. In Van Wagoner et al., JAMA 2017;318(20):2004-2010 (PMID 29183075), of 44 products sold as SARMs, only 52% actually contained the labeled SARM, 39% contained a different unapproved drug, and 9% contained no active compound at all. A buyer cannot know what a product marketed as "LGD-4033" actually contains without independent assay.

Legal status

How it compares

Ligandrol is often grouped with peptides used for muscle and recovery, but the honest comparison is that it is a small-molecule androgen-receptor drug, not a peptide, and it is not an approved therapy:

• Cardarine (GW-501516) — another non-peptide "research chemical" frequently stacked with SARMs. Cardarine is a PPARδ agonist, not a SARM and not a peptide; both are unapproved and WADA-prohibited, but they act on entirely different targets.
• CJC-1295 and Ipamorelin — actual peptides in the growth-hormone / muscle space. Unlike Ligandrol, these are peptides that work through the GH axis rather than the androgen receptor; all three are investigational or unapproved and none is a benchmarked, approved performance therapy.

The decisive difference: Ligandrol acts on the androgen receptor, suppresses the body's own testosterone even in short controlled use, and is linked to liver injury in case reports — with no approval anywhere. See the Muscle growth & hormone overview.

Common misconceptions

• "SARMs like Ligandrol are a mild, safe, or legal alternative to steroids." Not established, and not framed that way here. Even a controlled 21-day course suppressed testosterone and HDL at every dose, and LGD-4033 is linked to drug-induced liver injury in case reports. It is not approved for human use and is WADA-prohibited. "Selective" is a mechanistic hypothesis about tissue targeting, not a claim of safety.
• "Ligandrol is a peptide." No. It is a synthetic small molecule (C14H12F6N2O, 338.25 g/mol) that binds the androgen receptor. It is covered here only because it is discussed and stacked alongside peptides.
• "A product labelled 'LGD-4033' contains LGD-4033." Not reliably. In the JAMA 2017 analysis, 48% of products did not match their label — 39% contained a different unapproved drug and 9% contained nothing active. You cannot know the contents without an assay.
• "It passed trials, so it's proven safe." No. It reached only Phase 2; there is no Phase 3 and no approval. Long-term safety, the reversibility of suppression after real-world use, and the mechanism/frequency of the hepatotoxicity signal are all not established.

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This entry is educational and summarizes published research and public regulatory information. It is not medical advice, a recommendation, or a guide to obtaining or using any substance.