PPARδ Agonist • Oral • Research

GW-0742: The Selective PPARδ Endurance Compound

Last updated: March 2026

GW-0742 is a highly selective PPARδ agonist from GlaxoSmithKline's metabolic research program — structurally related to Cardarine (GW-501516) but with greater PPARδ selectivity over PPARα. Animal studies demonstrate endurance enhancement, fat oxidation, and favorable lipid profile changes. No human clinical trials exist.

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Typical Research Dose
Once daily oral
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Primary Target
High subtype selectivity
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VO₂max-equivalent gain
Rodent endurance study (animal)

How GW-0742 Works

GW-0742 activates PPARδ (peroxisome proliferator-activated receptor delta), a nuclear receptor that functions as a master regulator of fatty acid oxidation, mitochondrial biogenesis, and skeletal muscle fiber type. Unlike Cardarine, GW-0742 has minimal activity at PPARα, making it a cleaner tool for isolating PPARδ-specific effects in research.

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Selective PPARδ Activation

GW-0742 binds the PPARδ ligand-binding domain with high affinity and potency (EC₅₀ ~1 nM in cell assays). PPARδ is expressed highly in skeletal muscle, heart, and adipose tissue. Its activation drives transcriptional programs that shift cellular metabolism toward lipid utilization. GW-0742's selectivity ratio over PPARα is significantly higher than Cardarine's, reducing off-target PPARα signaling.

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Enhanced Fatty Acid Oxidation

Activated PPARδ upregulates key genes in fatty acid beta-oxidation: CPT1 (carnitine palmitoyltransferase), HADHA, and ACADL. These enzymes shuttle long-chain fatty acids into the mitochondria and oxidize them for ATP. In exercising skeletal muscle, this means more fat burned relative to glycogen — the metabolic basis of the endurance effect observed in rodent studies.

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Muscle Fiber Type Remodeling

PPARδ activation promotes expression of slow-twitch (Type I) oxidative muscle fiber characteristics in fast-twitch (Type II) fibers. In rodent models, chronic PPARδ agonist administration increased the proportion of oxidative, fatigue-resistant fiber markers, including myoglobin and mitochondrial density. This is the cellular basis for the dramatic endurance improvements seen in Cardarine and related compound studies.

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Lipid Profile Modulation

PPARδ agonism in liver and adipose tissue affects lipoprotein metabolism. Animal and some early human trial data with related compounds show: increased HDL cholesterol ("good" cholesterol), reduced LDL, reduced VLDL triglycerides, and suppression of hepatic lipid accumulation. GW-0742 demonstrated similar lipid-improving effects in dyslipidemic animal models, though human extrapolation remains speculative.

What Preclinical Studies Show

⚠️ All data below is from animal studies (primarily rodent models). No human clinical trial data exists for GW-0742. Where Cardarine (GW-501516) data is referenced for context, it is labeled. These figures are for research reference only.

Running Endurance Improvement vs Control
GW-0742 in sedentary mice treadmill model — animal study
~60%
HDL Cholesterol Increase
Dyslipidemic rodent model — animal study
~25-30%
Triglyceride Reduction
Hyperlipidemic rodent model — animal study
~30-40%
Fat Mass Reduction (diet-induced obesity model)
GW-0742 vs control — animal study
~15-20%
Type I Fiber Gene Expression Increase (skeletal muscle)
Oxidative fiber markers in rodent muscle — animal study
Significant
PPARδ Selectivity vs Cardarine (GW-501516)
Binding assay — PPARα:PPARδ ratio comparison
Higher selectivity

Side Effects & Risks

Carcinogenicity Risk (class concern)
Cardarine (related compound) showed multi-organ tumor promotion in rodents at high dose — long-term risk for GW-0742 is unknown
Unknown / High concern
Liver Enzyme Elevation
Observed at high doses in rodent studies; monitor ALT/AST
Low–Moderate
Hormonal Suppression
No AR activity — does not suppress testosterone axis
None (not androgenic)
GI Discomfort
Reported anecdotally — nausea, loose stools at higher doses
Low

Key Takeaways

✅ What We Know
  • Highly selective PPARδ agonist with minimal PPARα cross-activity
  • Animal studies show significant endurance gains (~60%) via oxidative fiber remodeling
  • Improves lipid panels: raises HDL, lowers triglycerides in dyslipidemic rodent models
  • Reduces fat mass in obesity rodent models via enhanced fatty acid oxidation
  • Does not suppress testosterone — not androgenic
  • More selective than Cardarine at the PPARδ receptor subtype
⚠️ What We Don't Know
  • No human clinical trials — zero human safety or efficacy data
  • Carcinogenicity risk: class-related compound (Cardarine) showed tumor promotion in rodents; GW-0742 long-term oncology data absent
  • Optimal human dose, half-life in humans, and bioavailability not characterized
  • Long-term cardiovascular effects at research doses unknown

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⚠️ Important Disclaimer

This page is for educational purposes only. It is not medical advice. GW-0742 is not FDA approved and is not intended for human use. All data referenced is from preclinical animal studies. The closely related compound Cardarine (GW-501516) was discontinued from clinical development due to carcinogenicity findings. Do not use any research chemical without consulting a qualified medical professional.