GW-0742

Overview

GW-0742 is a synthetic small-molecule PPARδ (PPAR-beta/delta) agonist developed by GlaxoSmithKline as a phenoxyacetic-acid/thiazole derivative—not a peptide or hormone. It exhibits ~1000-fold selectivity for human PPARδ (EC50 = 1.1 nM) over PPARα and PPARγ. Never advanced past preclinical development, GW-0742 has no approved human therapeutic use and no registered clinical trials. It is prohibited at all times under WADA as a member of the banned PPARδ-agonist class (Hormone and Metabolic Modulators), though not individually named on the list.

Mechanism of Action

GW-0742 is a high-affinity, highly selective agonist of human PPARδ (EC50 = 1.1 nM for hPPARδ transactivation vs ~1.1 µM for hPPARα and ~2 µM for hPPARγ), conferring ~1000-fold selectivity for PPARδ over the other PPAR subtypes. Upon activation, PPARδ heterodimerizes with RXR and binds PPAR-response elements (PPREs) to alter transcription of genes governing fatty-acid oxidation, glucose utilization, and inflammatory signaling. In mice, however, GW-0742-induced hepatomegaly, hepatic/skeletal-muscle peroxisome proliferation, and skeletal myopathy were shown to be predominantly mediated by off-target PPARα cross-activation rather than PPARδ—a mechanism-based toxicity concern at animal-study exposures.

Research Summary

No human efficacy or safety data exist; the only identified human exposure is a single 15 mg oral dose administered to volunteers solely to characterize urinary metabolites for an anti-doping detection assay—a bioanalytical study yielding no therapeutic or safety information. Preclinical rodent findings include: oral GW-0742 (30 mg/kg/day × 3 weeks) reduced right ventricular hypertrophy and systolic pressure in rats with chronic hypoxia-induced pulmonary hypertension but did not prevent pulmonary vascular remodeling; intraperitoneal GW-0742 (0.1 mg/kg) improved survival and reduced intestinal injury, leukocyte activation, cytokines, and apoptosis markers in a mouse gut ischemia/reperfusion model; and GW-0742 ameliorated hepatic steatosis, ER stress, and lung inflammation in various mouse models. Critically, mouse studies also demonstrated hepatomegaly, hepatic/skeletal-muscle peroxisome proliferation, and skeletal myopathy driven predominantly by off-target PPARα cross-activation, indicating mechanism-based toxicity risk.

Vendors selling GW-0742

Scored vendors carrying GW-0742, ranked by trust grade. Grades are computed from indexed Certificates of Analysis. Full $/mg pricing is on the comparison page.

Reported Side Effects

• Hepatomegaly (liver enlargement) observed in mice
• Hepatic and skeletal-muscle peroxisome proliferation (mouse studies)
• Skeletal myopathy driven by off-target PPARα cross-activation (mouse studies)
• No human safety data beyond single-dose bioanalytical exposure
• Prohibited at all times by WADA (PPARδ agonist class ban)

Compare GW-0742 with Others

Research References

• Novel selective small molecule agonists for peroxisome proliferator-activated receptor δ (PPARδ) — synthesis and biological activity. 2003. PMID 12699745.
• The PPARbeta/delta agonist GW0742 relaxes pulmonary vessels and limits right heart hypertrophy in rats with hypoxia-induced pulmonary hypertension. 2010. PMID 20209098.
• GW0742, a selective PPAR-beta/delta agonist, contributes to the resolution of inflammation after gut ischemia/reperfusion injury. 2010. PMID 20430778.
• PPAR alpha, more than PPAR delta, mediates the hepatic and skeletal muscle alterations induced by the PPAR agonist GW0742. 2008. PMID 18593727.

Frequently asked questions

Has GW-0742 been independently lab-tested?

Disclosed Labs has collected 3 Certificates of Analysis (COA) for GW-0742 from 2 independent testing labs. 1 vendor has submitted material for testing. Products average 99.6% tested purity across the corpus. Full testing data is available at https://www.disclosedlabs.com/peptides/gw-0742/testing.

What is the average purity of GW-0742 on the market?

Based on 3 COAs analyzed by Disclosed Labs, GW-0742 products average 99.6% (±0.3%) tested purity. Individual vendor results vary; see per-vendor COA data at https://www.disclosedlabs.com/peptides/gw-0742/coas.

Where can researchers source GW-0742?

1 vendor with Disclosed Labs trust grades currently list GW-0742, including Kimera Chems. Compare live prices and lab-verified COAs at https://www.disclosedlabs.com/prices/gw-0742.

How does GW-0742 work?

GW-0742 is a high-affinity, highly selective agonist of human PPARδ (EC50 = 1.1 nM for hPPARδ transactivation vs ~1.1 µM for hPPARα and ~2 µM for hPPARγ), conferring ~1000-fold selectivity for PPARδ over the other PPAR subtypes. Upon activation, PPARδ heterodimerizes with RXR and binds PPAR-response elements (PPREs) to alter transcription of genes governing fatty-acid oxidation, glucose utilization, and inflammatory signaling. In mice, however, GW-0742-induced hepatomegaly, hepatic/skeletal-muscle peroxisome proliferation, and skeletal myopathy were shown to be predominantly mediated by off-target PPARα cross-activation rather than PPARδ—a mechanism-based toxicity concern at animal-study exposures.

What does the research say about GW-0742?

No human efficacy or safety data exist; the only identified human exposure is a single 15 mg oral dose administered to volunteers solely to characterize urinary metabolites for an anti-doping detection assay—a bioanalytical study yielding no therapeutic or safety information. Preclinical rodent findings include: oral GW-0742 (30 mg/kg/day × 3 weeks) reduced right ventricular hypertrophy and systolic pressure in rats with chronic hypoxia-induced pulmonary hypertension but did not prevent pulmonary vascular remodeling; intraperitoneal GW-0742 (0.1 mg/kg) improved survival and reduced intestinal injury, leukocyte activation, cytokines, and apoptosis markers in a mouse gut ischemia/reperfusion model; and GW-0742 ameliorated hepatic steatosis, ER stress, and lung inflammation in various mouse models. Critically, mouse studies also demonstrated hepatomegaly, hepatic/skeletal-muscle peroxisome proliferation, and skeletal myopathy driven predominantly by off-target PPARα cross-activation, indicating mechanism-based toxicity risk.