---
title: "GW1516 (Cardarine)"
slug: "gw1516"
type: "compound"
category: "Body Composition"
url: "https://peptidesciencethailand.com/compounds/gw1516"
description: "A PPARdelta agonist studied for endurance performance and lipid metabolism in preclinical and early human research. Mechanism and evidence overview."
---
# GW1516 (Cardarine)

*PPAR-Delta Agonist, Reprogramming Metabolic Substrate Utilization and Endurance Capacity*

**Category:** Body Composition  
**Format:** Lyophilized Vial  
**Amount:** 10mg  
**Purity:** >99% (HPLC)

## Overview

GW1516, also known as GW501516, Cardarine, or Endurobol, is a synthetic selective agonist of the peroxisome proliferator-activated receptor delta (PPAR-delta), originally developed through a collaboration between GlaxoSmithKline and Ligand Pharmaceuticals in the early 2000s. With the molecular formula C21H18F3NO3S2 and a molecular weight of 453.50 g/mol, GW1516 is a small molecule research compound, not a peptide, steroid, or hormone. It represents a pharmacologically distinct class of metabolic modulators that directly reprogram cellular energy substrate utilization by activating the PPAR-delta nuclear receptor.

PPAR-delta is a ligand-activated nuclear transcription factor that plays a central role in regulating fatty acid metabolism, glucose homeostasis, inflammation, and cellular differentiation. It is widely expressed throughout the body, with particularly high levels in skeletal muscle, liver, adipose tissue, and the gastrointestinal tract. When activated by its ligand (in this case, GW1516), PPAR-delta forms a heterodimer with retinoid X receptor (RXR), binds to PPAR response elements (PPREs) in the promoter regions of target genes, and initiates the transcription of genes involved in fatty acid catabolism, mitochondrial biogenesis, and oxidative metabolism.

The primary metabolic effect of GW1516 is a fundamental shift in cellular fuel preference from glucose to fatty acids. This metabolic reprogramming occurs primarily in skeletal muscle, the largest metabolic organ in the body. GW1516 activates the transcription of genes encoding key enzymes in the fatty acid beta-oxidation pathway, including carnitine palmitoyltransferase 1 (CPT1), acyl-CoA dehydrogenases, and 3-hydroxyacyl-CoA dehydrogenase. Simultaneously, it upregulates genes involved in fatty acid transport and uptake, including fatty acid translocase (CD36) and fatty acid binding proteins (FABPs). This coordinated upregulation of fatty acid oxidation machinery enables muscle cells to derive a greater proportion of their energy from fat stores rather than glucose.

Research published in Cell demonstrated the remarkable metabolic effects of GW1516 in animal models. Mice treated with GW1516 exhibited a 68% increase in running endurance compared to controls, an effect attributed to the compound's ability to reprogram slow-twitch muscle fiber metabolism toward oxidative fat utilization. Gene expression analysis revealed upregulation of over 300 genes involved in fat metabolism, with concurrent downregulation of glycolytic genes, indicating a comprehensive shift in the muscle metabolic program. This finding earned GW1516 the informal designation as an exercise mimetic, as it produced metabolic adaptations typically requiring sustained aerobic training.

The interaction between GW1516 and the AMPK (AMP-activated protein kinase) signaling pathway adds another layer to its metabolic effects. Research published in Cell Metabolism showed that PPAR-delta activation by GW1516 synergizes with AMPK signaling to activate a transcriptional program that converts fast-twitch glycolytic (Type IIb) muscle fibers toward a slow-twitch oxidative (Type I) phenotype. This fiber-type transformation increases the proportion of fatigue-resistant, fat-burning muscle fibers and enhances overall oxidative capacity. When GW1516 was combined with exercise training in animal studies, the endurance-enhancing effects were additive, suggesting complementary rather than redundant mechanisms.

GW1516 also exerts significant effects on lipid profiles and cardiovascular risk markers. Clinical Phase II trials in humans demonstrated that GW1516 treatment (2.5mg and 10mg daily for 12 weeks) reduced LDL cholesterol, triglycerides, and apolipoprotein B while simultaneously increasing HDL cholesterol and shifting LDL particle distribution toward larger, less atherogenic particles. These lipid-modifying effects are mediated through PPAR-delta-dependent regulation of hepatic lipid metabolism, including increased expression of ABCA1 (a cholesterol efflux transporter) and reduced expression of genes involved in de novo lipogenesis.

The anti-inflammatory properties of GW1516 operate through PPAR-delta-mediated transcriptional repression of pro-inflammatory gene expression. PPAR-delta activation suppresses NF-kB signaling, a master regulator of inflammatory gene transcription, reducing the production of inflammatory cytokines including TNF-alpha, IL-6, and MCP-1. In macrophages, GW1516 promotes a shift from pro-inflammatory M1 polarization toward anti-inflammatory M2 polarization, reducing tissue inflammation. These anti-inflammatory effects have been demonstrated in models of atherosclerosis, metabolic syndrome, and inflammatory bowel disease.

GW1516 influences adipose tissue metabolism through direct PPAR-delta activation in adipocytes. The compound increases expression of uncoupling protein 1 (UCP1) in white adipose tissue, promoting thermogenesis and the browning of white fat. This thermogenic activation increases energy expenditure and contributes to the fat-reducing effects observed in animal models. Research has also demonstrated that GW1516 reduces adipose tissue inflammation and improves adipokine secretion profiles, normalizing the metabolic dysfunction associated with obesity.

It is essential to note the safety considerations associated with GW1516 research. GlaxoSmithKline discontinued clinical development of GW1516 in 2007 after long-term animal toxicology studies (conducted at doses significantly exceeding those used in human trials and administered over the animals' lifetime) revealed an increased incidence of tumors in multiple organ sites. These findings have been debated in the scientific literature, with some researchers noting the extreme dose levels and durations used in the toxicology studies, but the carcinogenicity signal led to the termination of the clinical program. This safety concern is a critical consideration in any research context involving GW1516.

Despite the discontinuation of clinical development, GW1516 remains an important research tool for studying PPAR-delta biology, metabolic reprogramming, and the molecular mechanisms of endurance physiology. It is prohibited by WADA in competitive athletics and is classified as a Gene and Cellular Doping substance. All research with GW1516 requires comprehensive medical oversight and informed risk assessment.

## Mechanism of Action

### Step 1: PPAR-Delta Receptor Activation

GW1516 binds to the ligand-binding domain of PPAR-delta, inducing a conformational change that promotes heterodimerization with RXR and binding to PPAR response elements (PPREs) in target gene promoters.

### Step 2: Fatty Acid Oxidation Gene Transcription

Activated PPAR-delta/RXR heterodimers drive transcription of fatty acid catabolism genes including CPT1, acyl-CoA dehydrogenases, CD36, and FABPs, upregulating the entire beta-oxidation machinery in skeletal muscle.

### Step 3: Metabolic Substrate Switch

The coordinated upregulation of fat oxidation enzymes and transporters shifts cellular fuel preference from glucose to fatty acids. Glycolytic gene expression is concurrently downregulated, producing a comprehensive metabolic reprogramming.

### Step 4: AMPK Synergy and Fiber-Type Transformation

PPAR-delta activation synergizes with AMPK signaling to promote conversion of glycolytic Type IIb muscle fibers toward oxidative Type I fibers, increasing the proportion of fatigue-resistant, fat-burning muscle and enhancing aerobic capacity.

### Step 5: Systemic Metabolic Improvement

Downstream effects include improved lipid profiles (reduced LDL, increased HDL), enhanced thermogenesis in adipose tissue through UCP1 upregulation, suppression of NF-kB-mediated inflammation, and increased overall endurance capacity.

## Researched Benefits

### Enhanced Endurance Capacity

Animal studies demonstrated a 68% increase in running endurance with GW1516 treatment, driven by metabolic reprogramming of skeletal muscle toward fatty acid oxidation. Gene expression analysis revealed upregulation of over 300 metabolic genes, producing adaptations that mimic the effects of sustained aerobic training.

### Improved Lipid Profiles

Phase II human clinical trials showed that GW1516 reduced LDL cholesterol, triglycerides, and apolipoprotein B while increasing HDL cholesterol. It also shifted LDL particle distribution toward larger, less atherogenic particles, producing a comprehensive improvement in cardiovascular lipid markers.

### Fat Metabolism Activation

GW1516 shifts cellular energy production from glucose utilization to fatty acid beta-oxidation in skeletal muscle. It additionally promotes thermogenesis in white adipose tissue through UCP1 upregulation, increasing energy expenditure and reducing fat accumulation in preclinical models.

### Anti-Inflammatory Metabolic Effects

Through PPAR-delta-mediated suppression of NF-kB signaling and promotion of anti-inflammatory M2 macrophage polarization, GW1516 reduces systemic inflammation. These effects have been demonstrated in models of atherosclerosis and metabolic syndrome, complementing its lipid-modifying activity.

## Dosage & Administration

| Parameter | Detail |
| --- | --- |
| Protocol | 10-20mg per day, administered orally once daily |
| Route | Oral administration |
| Duration | 6-8 week cycles in research settings |
| Cycle Notes | Research protocols typically employ 10-20mg daily dosing for 6-8 weeks. GW1516 does not suppress the HPG axis and does not require post-cycle therapy. However, the safety considerations associated with long-term PPAR-delta agonism necessitate conservative cycle durations and comprehensive medical monitoring. |
| Reconstitution | For lyophilized research-grade formulations, reconstitute with appropriate solvent per protocol. GW1516 is commonly administered in oral solution or capsule form for research use. |

> **Specialist note:** A your specialist will conduct comprehensive risk assessment before initiating any GW1516 research protocol. Baseline and periodic monitoring of liver function, complete blood count, lipid panels, and fasting glucose is essential. Individuals with a personal or family history of cancer, liver disease, or metabolic disorders require careful evaluation. The compound's safety profile at standard research doses remains a subject of ongoing scientific discussion.

## Compound Reference Data

| Property | Value |
| --- | --- |
| Format | Lyophilized Powder |
| Amount | 10mg per vial |
| Purity | >99% |
| Purity Method | HPLC (High-Performance Liquid Chromatography) |
| Composition | GW501516 (Cardarine), PPAR-delta agonist |
| Molecular Weight | 453.50 g/mol |
| Storage | Store at -20°C or 2-8°C in a dry, light-protected environment. |
| Appearance | White to off-white powder |

## Medical Guidance

GW1516 is a PPAR-delta agonist with broad metabolic effects on lipid metabolism, glucose homeostasis, and inflammatory signaling. Long-term animal toxicology studies at high doses revealed carcinogenicity signals that led to discontinuation of clinical development. Any research use requires comprehensive specialist oversight, thorough risk-benefit assessment, conservative dosing, and regular monitoring of liver function and general health markers. Individuals with any history of malignancy, pre-malignant conditions, or elevated cancer risk factors should not participate in GW1516 research protocols.

## Frequently Asked Questions

### What is GW1516 and is it a peptide or SARM?

GW1516 (Cardarine) is neither a peptide nor a SARM. It is a selective PPAR-delta receptor agonist, a class of compounds that activate nuclear transcription factors to reprogram cellular metabolism. Unlike SARMs, it does not interact with androgen receptors and does not affect testosterone or hormonal axes. It is a metabolic modulator that shifts energy substrate utilization from glucose toward fatty acid oxidation.

### Why was clinical development of GW1516 discontinued?

GlaxoSmithKline discontinued GW1516 development in 2007 after long-term animal toxicology studies showed increased tumor incidence in multiple organs. These studies used doses substantially higher than those tested in humans and administered the compound over the animals' lifetime. The relevance of these high-dose, chronic exposure findings to short-term, lower-dose human use remains debated in the scientific literature, but the carcinogenicity signal was sufficient to halt the clinical program.

### Does GW1516 suppress testosterone or require post-cycle therapy?

No. GW1516 does not interact with androgen receptors and does not suppress the hypothalamic-pituitary-gonadal axis. It does not affect testosterone, LH, FSH, or estrogen levels. Post-cycle therapy is not required from a hormonal perspective. However, periodic health monitoring is recommended due to the compound's broad metabolic effects.

### How does GW1516 increase endurance?

GW1516 activates PPAR-delta in skeletal muscle, triggering transcription of genes involved in fatty acid oxidation while downregulating glycolytic genes. This reprograms muscle cells to derive energy preferentially from fat rather than glucose. When synergized with AMPK signaling, it promotes muscle fiber-type transformation toward fatigue-resistant oxidative fibers. Animal studies showed a 68% increase in running distance with treatment.

### Is GW1516 prohibited in competitive sports?

Yes. GW1516 has been prohibited by the World Anti-Doping Agency (WADA) since 2009, classified under S4.5 (Metabolic Modulators). WADA took the unusual step of issuing a direct warning to athletes about GW1516 in 2013 due to safety concerns. Multiple athletes across cycling, triathlon, and other endurance sports have received suspensions for positive GW1516 tests. This compound is intended exclusively for supervised research applications.

## Related Compounds

- /compounds/aod-9604
- /compounds/tesamorelin
- /compounds/mk-677