GW-501516

GW-501516 (Cardarine)

GW-501516 (also identified as GW 1516, GSK-516, or Cardarine) is a synthetic, non-steroidal agonist of the peroxisome proliferator-activated receptor delta (PPARδ / PPARβ-δ). Originally developed by GlaxoSmithKline with Ligand Pharmaceuticals, it serves as the reference PPARδ ligand in the primary literature.

Technical Specifications

Mechanism of Action & Selectivity

GW-501516 binds to the PPARδ ligand-binding domain, facilitating heterodimerization with RXR and promoting transcription at peroxisome proliferator response elements (PPREs). This process modulates genes involved in fatty acid transport, β-oxidation, and mitochondrial biogenesis.

• Binding Affinity: In human PPARδ binding assays, the compound demonstrates a Ki of 1.1 nM.

• Transactivation Potency: It exhibits an EC50 of 1.2 nM in GAL4 reporter transactivation assays.

• Selectivity: It is >1,000-fold selective for PPARδ over PPARα and PPARγ, allowing for clean tool-compound application.

Research Background & Safety Context

• Development History: GW-501516 was discontinued from clinical development following long-term rodent carcinogenicity findings across multiple organ systems.

• Regulatory/Prohibited Status: It was added to the WADA Prohibited List in 2009 as a metabolic modulator following the 2007 endurance research that generated a doping market. WADA has issued separate public warnings regarding the compound’s toxicity.

Research Applications

• PPARδ Studies: Used for mapping binding, transactivation, and downstream gene expression profiles.

• Receptor Selectivity: Investigating nuclear receptor subtype selectivity and structure-activity relationships (SAR) across PPAR isoforms.

• Metabolic Research: Studies focused on fatty acid oxidation, cholesterol transport, and mitochondrial biogenesis.

• Analytical Standards: Utilized as an analytical reference standard for anti-doping LC-MS/MS method development.

• Comparative Panels: Used in comparative PPAR agonist panels alongside GW-0742 and GW7647.

Research Use Disclaimer

Research Use Only Disclaimer: This product is developed and distributed strictly as a Research Use Only (RUO) laboratory reference material intended exclusively for non-clinical analytical and scientific investigation. It is not an FDA-approved drug formulation, active pharmaceutical ingredient, therapeutic agent, cosmetic, or dietary supplement, and is strictly prohibited for human or veterinary consumption. No dosing information is provided or implied.