GW-0742 Overview
GW-0742 (also designated GW-610742, GW-0742X) is a synthetic small-molecule agonist of peroxisome proliferator-activated receptor delta (PPAR-δ, also written PPARβ/δ), originally developed by GlaxoSmithKline. In published in vitro work, GW-0742 has been characterized as one of the most potent and selective PPAR-δ ligands described to date, with reported EC₅₀ values of approximately 1 nM at human PPAR-δ and roughly 1,000-fold selectivity over human PPAR-α and PPAR-γ.
GW-0742 is widely cited in the primary literature as a reference PPAR-δ agonist in studies of nuclear receptor signaling, lipid and fatty acid oxidation pathways, inflammation, and tissue protection models.
GW-0742 is not approved for human or veterinary use and is supplied strictly for laboratory and analytical research purposes.
Mechanism of Action
GW-0742 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 uptake and oxidation, mitochondrial function, and inflammatory signaling.
Reported in vitro and preclinical characterizations include:
- PPAR-δ EC₅₀ ≈ 1 nM (human reporter assays)
- ~1,000-fold selectivity over PPAR-α and PPAR-γ
- Activity reported in cardiomyocyte, vascular endothelial, hepatic, neuronal, and immune cell models
- At high concentrations and extended exposure (e.g., 100 μM, 48 h), GW-0742 has been reported to induce apoptotic cell death in cerebellar granule neuronal cultures, underscoring its research-use-only status
Chemical Structure
- Chemical Name: 2-[4-[[[2-[3-fluoro-4-(trifluoromethyl)phenyl]-4-methyl-5-thiazolyl]methyl]thio]-2-methylphenoxy]-acetic acid
- Synonyms: GW0742; GW-0742X; GW-610742; GW 610742
- CAS Number: 317318-84-6
- Molecular Formula: C₂₁H₁₇F₄NO₃S₂
- Molecular Weight: 471.49 g/mol
- PubChem CID: 9934458
Structural Description: GW-0742 is a small-molecule, nonsteroidal PPAR-δ ligand built around a 1,3-thiazole core flanked by a 3-fluoro-4-(trifluoromethyl)phenyl group and a phenoxyacetic acid tail linked via a methylenethio bridge. The four fluorine atoms and the two sulfur centers (one in the thiazole, one in the sulfide linker) are key structural features contributing to its receptor affinity and subtype selectivity. Structural identification and molecular data are referenced against PubChem.
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
PPAR-δ agonists in the GW series, including GW-0742 and the related compound GW-501516, were initially advanced through pharmaceutical development programs and subsequently discontinued from clinical development following long-term rodent carcinogenicity findings. This published toxicology profile is part of the scientific record on the compound and reinforces that GW-0742 is supplied strictly as a research reagent for laboratory and analytical use, not for any therapeutic application.
Research Focus Areas
GW-0742 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 and fatty acid oxidation signaling pathway research
- Cardiovascular, hepatic, and neuronal protection models in published preclinical literature
- Inflammatory and immune cell signaling studies
- Analytical method development and reference-standard work
Research Use Disclaimer
GW-0742 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-0742 is a structurally defined, highly selective PPAR-δ agonist with extensive primary-literature support as a reference ligand in nuclear receptor pharmacology, lipid metabolism signaling, and tissue protection models. Its receptor selectivity, well-characterized potency, and documented research utility make it a widely used compound in controlled laboratory investigations of PPAR-δ biology.
| CAS Number | 317318-84-6 |
| Other Names | GW0742, GW 0742, GW0742X, GW-0742X, 4PZK9FJC4Z, CHEMBL38508, DTXSID9040760, CHEBI:79991, GW 0742X, SR-05000000447, 3tkm |
| IUPAC Name | [4-[[[2-[3-fluoro-4-(trifluoromethyl)phenyl]-4-methyl-5-thiazolyl]methyl]thio]-2-methyl phenoxy]-acetic acid[1] |
| Molecular Formula | C₂₁H₁₇F₄NO₃S₂ |
| Molecular Weight | 471.5 |
| Dry-Fill Capsule Concentration | 10mg |
| Liquid Concentration And Solution | 20mg/ml PEG400, DMSO |
| Aliquot Concentration And Solution | 50mg/ml PEG400, Propylene Glycol, Benzyl Benzoate, Benzyl Alcohol |
