Chemistry on this one is actually correct — first one in the audit that didn’t have an error. CAS, formula, MW, and IUPAC name all check out.
Other accurate data points worth incorporating:
- IC₅₀ at human PPAR-δ ≈ 1 nM, ≥100-fold selectivity over PPAR-α and PPAR-γ
- PubChem CID: 9803963
- Additional synonyms: GW 1516, GSK-516, Endurobol
- GSK halted clinical development specifically due to multi-organ carcinogenicity in long-term rodent studies (the original cause of the WADA ban)
- WADA Prohibited List, currently classified under “Other anabolic agents” / metabolic modulators
Rewrite:
GW-501516 Overview
GW-501516 (also designated GW 1516, GSK-516, and commonly referenced as Cardarine) is a synthetic small-molecule agonist of peroxisome proliferator-activated receptor delta (PPAR-δ, also written PPARβ/δ), originally developed by GlaxoSmithKline. It has been extensively cited in the primary literature as a reference PPAR-δ ligand in studies of lipid metabolism, fatty acid oxidation, mitochondrial function, and inflammatory and metabolic signaling pathways. GW-501516 is widely characterized as one of the most potent and selective PPAR-δ agonists described, with reported binding affinity in the low-nanomolar range and substantial selectivity over the other PPAR subtypes.
GW-501516 is not approved for human or veterinary use and is supplied strictly for laboratory and analytical research purposes.
Mechanism of Action
GW-501516 binds the ligand-binding domain of PPAR-δ and acts as a high-affinity agonist. Upon activation, PPAR-δ heterodimerizes with the retinoid X receptor (RXR) and binds peroxisome proliferator response elements (PPREs) in target gene promoters, modulating transcription of genes involved in fatty acid transport, β-oxidation, mitochondrial biogenesis, and cellular lipid handling.
Reported in vitro and preclinical characterizations include:
- PPAR-δ binding IC₅₀ ≈ 1 nM (human reporter assays)
- ≥100-fold selectivity over PPAR-α and PPAR-γ
- Activity reported in skeletal muscle, hepatic, adipose, vascular endothelial, and immune cell models
- Documented modulation of IL-6/STAT3 inflammatory signaling and reverse cholesterol transport pathways in published primate and rodent studies
Chemical Structure
- Chemical Name: 2-[2-Methyl-4-[[4-methyl-2-[4-(trifluoromethyl)phenyl]-1,3-thiazol-5-yl]methylsulfanyl]phenoxy]acetic acid
- Synonyms: GW501516; GW 1516; GSK-516; Cardarine; Endurobol
- CAS Number: 317318-70-0
- Molecular Formula: C₂₁H₁₈F₃NO₃S₂
- Molecular Weight: 453.49 g/mol
- PubChem CID: 9803963
Structural Description: GW-501516 is a small-molecule, nonsteroidal PPAR-δ ligand built around a 1,3-thiazole core flanked by a 4-(trifluoromethyl)phenyl group and a phenoxyacetic acid tail linked via a methylenethio bridge. The trifluoromethyl group and the two sulfur centers (one in the thiazole ring, one in the sulfide linker) are key structural features contributing to receptor affinity and subtype selectivity. Structural identification and molecular data are referenced against PubChem.
GW-501516 is structurally closely related to GW-0742, differing by a single aromatic fluorine substituent — the two compounds are frequently compared in PPAR-δ structure-activity studies.
Physical and Chemical Properties
- Appearance: White to off-white crystalline powder
- Solubility: Soluble in DMSO; poorly soluble in water
- Stability: Stable under dry, cool, light-protected storage conditions
- Recommended storage: -20 °C for long-term stability
Research Background and Safety Context
GW-501516 was advanced through pharmaceutical development programs and subsequently discontinued from clinical development following long-term rodent carcinogenicity findings, which were reported across multiple organ systems and dose levels. As a result, GW-501516 is included on the World Anti-Doping Agency (WADA) Prohibited List under the metabolic modulators category. This published toxicology and regulatory record is part of the scientific literature on the compound and reinforces that GW-501516 is supplied strictly as a research reagent for laboratory and analytical use, not for any therapeutic or performance-related application.
Research Focus Areas
GW-501516 is commonly referenced in laboratory research involving:
- PPAR-δ binding, transactivation, and downstream gene expression studies
- Nuclear receptor selectivity and structure-activity analysis across PPAR subtypes
- Lipid metabolism, fatty acid oxidation, and cholesterol transport signaling research
- Inflammatory and immune cell signaling studies (including IL-6/STAT3 pathway research)
- Analytical method development and reference-standard work, including LC-MS/MS panels referenced in anti-doping analytical literature
- Comparative PPAR agonist studies alongside GW-0742, fenofibrate, and related ligands
Research Use Disclaimer
GW-501516 is intended strictly for laboratory research use only (RUO). Not for human consumption, clinical use, veterinary use, or diagnostic application. All handling and use must comply with applicable laws, regulations, and institutional laboratory safety standards.
Summary
GW-501516 is a structurally defined, highly selective PPAR-δ agonist with extensive primary-literature support as a reference ligand in nuclear receptor pharmacology, lipid metabolism, and inflammatory signaling research. Its receptor selectivity, well-characterized potency, and documented research utility make it a widely studied compound in controlled laboratory investigations of PPAR-δ biology.
| CAS Number | 317318-70-0 |
| Other Names | GW501516, GW 501516, GW-501516, Cardarine, Endurobol, GSK-516, GW1516, GW 1516, UNII-7I2HA1NU22 |
| IUPAC Name | 2-[2-methyl-4-[[4-methyl-2-[4-(trifluoromethyl)phenyl]-1,3-thiazol-5-yl]methylsulfanyl]phenoxy]acetic acid |
| Molecular Formula | C₂₁H₁₈F₃NO₃S₂ |
| Molecular Weight | 453.5 |
| Dry-Fill Capsule Concentration | 10mg |
| Liquid Concentration And Solution | 30mg/ml PEG400, DMSO |
| Aliquot Concentration And Solution | 50mg/ml PEG400, Propylene Glycol, Benzyl Benzoate, Benzyl Alcohol |
