For laboratory research use only. Not for human consumption. All compounds referenced in this article are sold by Explicit SARMs solely as reference materials for in-vitro and animal research by qualified professionals. Nothing here is medical advice, and no statement has been evaluated by the FDA. These materials are not intended to diagnose, treat, cure or prevent any disease.
LGD-4033, known by the trade-style name Ligandrol and later by the development code VK5211, is a nonsteroidal selective androgen receptor modulator (SARM) with one of the clearer clinical development records in the class. It has a published phase 1 study in healthy volunteers and a completed phase 2 study in older patients recovering from hip fracture. That combination of animal pharmacology and controlled clinical data makes it a common subject of androgen receptor research.
This review covers what LGD-4033 is, how it acts on the androgen receptor, how its development progressed, and what laboratories should consider for documentation and handling. Explicit SARMs supplies LGD-4033 Ligandrol Capsules and LGD-4033 Liquid strictly as reference material for laboratory research.
What Is LGD-4033?
LGD-4033 is a nonsteroidal androgen receptor ligand built on a pyrrolidinyl-benzonitrile scaffold. It is chemically distinct from the aryl-propionamide SARMs such as Ostarine and from the scaffold of RAD-140, although all three target the same receptor.
- Common names: LGD-4033, Ligandrol, VK5211
- Class: nonsteroidal selective androgen receptor modulator
- Primary target: androgen receptor
- Originator: Ligand Pharmaceuticals; later licensed to Viking Therapeutics
- Regulatory status: not approved by the FDA or any other regulator for any indication
Mechanism of Action
Like other SARMs, LGD-4033 binds the ligand-binding domain of the androgen receptor, triggering nuclear translocation, DNA binding at androgen response elements, and recruitment of coregulator proteins. Its reported tissue selectivity in preclinical models rests on the same principles that apply across the class: it is not converted to DHT by 5-alpha reductase, it is not aromatized to estradiol, and the receptor conformation it induces recruits coregulators differently from endogenous androgens. [4]
LGD-4033 is described in the literature as binding the androgen receptor with high affinity and selectivity relative to other steroid receptors. Its long elimination half-life in humans, reported in the phase 1 study, is a practical consideration for analytical work, because it extends the window over which parent compound and metabolites can be detected. [1][5]
Research History
Ligand Pharmaceuticals developed LGD-4033 in the 2000s with conditions involving loss of muscle and bone in mind, such as age-related decline and muscle wasting. Preclinical work in rodents characterized its anabolic activity in muscle and bone relative to its effects on the prostate.
The first controlled human data were published in 2013 by Basaria and colleagues. [1] Viking Therapeutics subsequently licensed the compound, renamed it VK5211, and ran a phase 2 trial in patients aged 65 and over recovering from acute hip fracture (NCT02578095). That trial is listed as completed on ClinicalTrials.gov.
What Published Studies Report
Phase 1 study
The 2013 study in the Journals of Gerontology was a randomized, double-blind, placebo-controlled trial in healthy young men over 21 days. [1] The authors reported that LGD-4033 was well tolerated over that short period, had a long elimination half-life, and produced dose-dependent suppression of total testosterone, sex hormone-binding globulin, HDL cholesterol and triglycerides. They also reported increases in lean body mass by DXA. The study was short and small, and the authors described it as an early safety and pharmacokinetic study rather than evidence of clinical benefit.
Hip fracture trial
The Viking phase 2 trial (NCT02578095) evaluated VK5211 against placebo in older patients after hip fracture surgery. The sponsor reported lean body mass changes as the primary endpoint, with functional measures as secondary endpoints. Viking has not taken the compound into phase 3.
Animal research
In ovariectomized rats, Roch and colleagues compared LGD-4033 with Ostarine and reported changes in muscle tissue characteristics, including fiber size and capillarization, with some effects on other organs that varied by exposure. [2] This is one of the few direct head-to-head comparisons of two SARMs in the same model.
Adverse event reports
Case reports describe drug-induced liver injury associated with unregulated products labeled as containing LGD-4033, sometimes combined with RAD-140. [3] The composition of those products was not verified, which limits causal interpretation, but hepatic endpoints are clearly relevant to study design.
Research Considerations
- Long half-life. In pharmacokinetic and washout designs, allow for slow elimination and include enough sampling time points.
- Endocrine suppression. The phase 1 data show dose-dependent suppression of testosterone and SHBG. Animal protocols that measure HPG-axis hormones should include vehicle controls and recovery time points. [1]
- Lipids and liver. HDL reduction and the hepatic case literature support including lipid and liver panels as secondary endpoints. [1][3]
- Metabolite analysis. Anti-doping laboratories have characterized LGD-4033 metabolites in detail, and that literature is useful for anyone developing LC-MS methods. [5]
- Reference standards. Validate methods against an authenticated standard and record lot numbers.
How LGD-4033 Compares With Other SARMs
LGD-4033 occupies a middle position in the SARM evidence base. It has more human data than RAD-140, S-23 or YK-11, but far less than Ostarine. Its distinguishing features in the literature are:
- Potency. The phase 1 study reported measurable, dose-dependent hormonal suppression at very small exposures, which indicates high potency at the androgen receptor. [1]
- Long half-life. Its elimination half-life in humans was reported as long, with accumulation on repeated administration, which is relevant to washout design in comparative studies. [1]
- Distinct scaffold. Its pyrrolidinyl-benzonitrile structure differs from the aryl-propionamides, which makes it a useful structural comparator in receptor pharmacology work.
In head-to-head animal work, the ovariectomized rat study by Roch and colleagues remains the clearest direct comparison with Ostarine. [2]
WADA Status
LGD-4033 (ligandrol) is named explicitly in WADA section S1.2 (Other Anabolic Agents) and is prohibited at all times. [6]
Storage, Purity and COA
- Store sealed and protected from light, heat and humidity.
- Keep liquid material tightly capped to prevent solvent loss and concentration drift.
- Log lot numbers and receipt dates with every experiment.
- Review the lot-specific Certificate of Analysis. A credible COA reports HPLC purity, confirms identity by mass spectrometry, and lists the lot number and test date.
For lot documentation, use the contact page.
Related Research Compounds
- RAD-140 Testolone Capsules, a nonsteroidal SARM with a phase 1 oncology dataset
- Ostarine MK-2866 Capsules, the comparator in the ovariectomized rat study [2]
- YK-11 Myostine Capsules, a steroidal AR partial agonist studied in cell models (see the YK-11 research overview)
- Class overview: SARMs vs Traditional Research Compounds and the SARMs collection
Frequently Asked Questions
Are LGD-4033, Ligandrol and VK5211 the same compound?
Yes. LGD-4033 was the original Ligand Pharmaceuticals code, Ligandrol is a trade-style name, and VK5211 is the Viking Therapeutics development code.
Is LGD-4033 approved by the FDA?
No. It has been studied in phase 1 and phase 2 trials but has never been approved by the FDA or any other regulator.
What did the phase 1 study find?
Over 21 days in healthy young men, the investigators reported a long half-life, dose-dependent suppression of testosterone, SHBG and HDL cholesterol, and increases in lean body mass. [1]
Why is LGD-4033 relevant to anti-doping research?
It is prohibited by WADA, and its long half-life and persistent metabolites have made it a frequent subject of detection-method studies. [5][6]
What is the difference between the capsule and liquid formats?
The compound is the same. Capsules provide pre-measured solid material, and the liquid suits protocols based on preparing solutions.
Why does the long half-life matter for research?
A long elimination half-life means the compound and its metabolites remain measurable for an extended period after exposure ends. That affects washout periods in crossover designs and makes LGD-4033 a common target in detection-window studies. [1][5]
What endpoints are most relevant in animal studies?
Based on the published record, HPG-axis hormones, lipid panels, liver enzymes and androgen-dependent tissue weights are the most informative endpoints. [1][3]
References
- Basaria S, et al. The safety, pharmacokinetics, and effects of LGD-4033, a novel nonsteroidal oral, selective androgen receptor modulator, in healthy young men. J Gerontol A Biol Sci Med Sci. 2013. PubMed 22459616
- Roch PJ, et al. Ostarine and Ligandrol Improve Muscle Tissue in an Ovariectomized Rat Model. Front Endocrinol (Lausanne). 2020. PubMed 33042018
- Barbara M, et al. Drug-Induced Liver Injury Associated With Alpha Bolic (RAD-140) and Alpha Elite (RAD-140 and LGD-4033). ACG Case Rep J. 2020. PubMed 33062783
- Narayanan R, et al. Development of selective androgen receptor modulators (SARMs). Mol Cell Endocrinol. 2018. PubMed 28624515
- Thevis M, Schanzer W. Detection of SARMs in doping control analysis. Mol Cell Endocrinol. 2018. PubMed 28137616
- World Anti-Doping Agency. 2026 Prohibited List. wada-ama.org
- ClinicalTrials.gov. Acute Hip Fracture Study in Patients 65 Years or Greater (VK5211; Viking Therapeutics). NCT02578095
For laboratory research use only. Not for human consumption. All compounds referenced in this article are sold by Explicit SARMs solely as reference materials for in-vitro and animal research by qualified professionals. Nothing here is medical advice, and no statement has been evaluated by the FDA. These materials are not intended to diagnose, treat, cure or prevent any disease.