LGD-4033 (Ligandrol) Overview
LGD-4033, also known as Ligandrol and by the developmental designation VK-5211, is a synthetic, orally bioavailable nonsteroidal selective androgen receptor modulator (SARM) originally developed by Ligand Pharmaceuticals and subsequently advanced under license by Viking Therapeutics. It is one of the most extensively studied SARMs in the published literature, characterized as a high-affinity androgen receptor ligand with reported binding K_i of approximately 1 nM and substantial selectivity over other steroid hormone receptors.
LGD-4033 has been advanced through Phase I and Phase II clinical research investigations and is widely cited as a reference compound in androgen receptor pharmacology, SARM structure-activity studies, anti-doping analytical chemistry, and pharmacokinetic and metabolism research.
LGD-4033 is not approved for human or veterinary use and is supplied strictly for laboratory and analytical research purposes.
Mechanism of Action
LGD-4033 binds the androgen receptor ligand-binding domain with high affinity and acts as a tissue-differential AR ligand. Published in vitro and preclinical characterizations describe a pattern of differential transcriptional output across androgen-responsive cell types, with full-agonist activity in muscle- and bone-derived cell models and reduced (partial agonist) activity in prostate-derived reporter models.
Reported characterizations include:
- AR binding K_i ≈ 1 nM
- Oral bioavailability in published rodent and human pharmacokinetic studies
- Non-aromatizable nonsteroidal scaffold
- Distinct AR ligand-binding domain conformational pattern relative to testosterone and steroidal androgens
- Documented in vitro metabolite profile relevant for analytical and forensic research
Chemical Structure & Identification
- Chemical Name: 4-[(2R)-2-[(1R)-2,2,2-Trifluoro-1-hydroxyethyl]pyrrolidin-1-yl]-2-(trifluoromethyl)benzonitrile
- Synonyms: LGD4033; LGD 4033; Ligandrol; VK-5211; VK5211
- CAS Number: 1165910-22-4
- Molecular Formula: C₁₄H₁₂F₆N₂O
- Molecular Weight: 338.25 g/mol
- Exact Mass: 338.0854
- PubChem CID: 44137686
- UNII: 1EJT54415A
- InChIKey: OPSIVAKKLQRWKC-VXGBXAGGSA-N
Structural Description: LGD-4033 is a small-molecule, nonsteroidal androgen receptor ligand built on a benzonitrile scaffold with a 2-(trifluoromethyl) substituent and a 4-substituted (R,R)-2-(2,2,2-trifluoro-1-hydroxyethyl)pyrrolidinyl group. The two stereocenters and the two trifluoro substituents contribute to receptor binding affinity, metabolic stability, and the compound’s distinctive chemical signature in mass spectrometric analysis. Structural classification places LGD-4033 within the phenylpyrrolidine chemical class. Structural identification and molecular data are referenced against PubChem.
Physical and Chemical Properties
- Appearance: White to off-white solid
- Solubility: Soluble in DMSO; poorly soluble in water
- LogP (predicted): ~3.6–3.7
- Melting point: ~108–111 °C
- Stability: Stable under dry, cool, light-protected storage conditions
- Recommended storage: -20 °C for long-term stability
Research Focus Areas
LGD-4033 is commonly referenced in laboratory research involving:
- Androgen receptor binding, competition, and transactivation assays
- SARM structure-activity relationship (SAR) analysis, particularly within the phenylpyrrolidine class
- Nuclear receptor selectivity profiling
- AR ligand-binding domain conformation and coregulator recruitment studies
- Analytical and reference-standard work, including extensive LC-MS/MS method development referenced in anti-doping analytical literature
- In vitro metabolism, ADME, and forensic toxicology research (LGD-4033 metabolite identification is well-characterized in the published literature)
- Comparative SARM evaluation alongside other Ligand Pharmaceuticals compounds (LGD-3303, LGD-2226) and the broader nonsteroidal AR ligand class
Research Background & Regulatory Context
LGD-4033 is included on the World Anti-Doping Agency (WADA) Prohibited List under the anabolic agents category and is among the most frequently detected SARM analytes in anti-doping testing programs. The U.S. Food and Drug Administration has issued public consumer advisories specifically naming Ligandrol in the context of unapproved bodybuilding supplements. This published regulatory and analytical record is part of the scientific literature on the compound and reinforces that LGD-4033 is supplied strictly as a research reagent for laboratory and analytical use, not for any therapeutic, performance, or supplement-related application.
Research Use Disclaimer
LGD-4033 is intended strictly for laboratory research use only (RUO). Not for human consumption, clinical use, veterinary use, therapeutic application, dietary supplement use, or diagnostic purposes. All handling and use must comply with applicable federal, state, and local laws and institutional laboratory safety standards.
Summary
LGD-4033 (Ligandrol) is a structurally defined, well-characterized nonsteroidal selective androgen receptor modulator with extensive primary-literature support as a reference ligand in androgen receptor pharmacology, SARM SAR research, and anti-doping analytical method development. Its phenylpyrrolidine scaffold and detailed binding, pharmacokinetic, and metabolite profiles make it a widely used reference compound in controlled laboratory studies of androgen receptor signaling.
| CAS Number | 1165910-22-4 |
| Other Names | LGD4033, LGD 4033, Ligandrol, UNII-1EJT54415Am, VK-5211, 1EJT54415A, SCHEMBL221159, CHEMBL5170587 |
| IUPAC Name | 4-[(2R)-2-[(1R)-2,2,2-trifluoro-1-hydroxyethyl]pyrrolidin-1-yl]-2-(trifluoromethyl)benzonitrile |
| Molecular Formula | C₁₄H₁₂F₆N₂O |
| Molecular Weight | 338.25 |
| Dry-Fill Capsule Concentration | 7.5mg |
| Liquid Concentration And Solution | 20mg/ml (PEG400) |
| Aliquot Concentration And Solution | 50mg/ml (MCT, Benzyl Benzoate, Benzyl alcohol) |
