GW0742 60 caps

Chemical reagent intended exclusively for laboratory tests (Research Use Only). It is not a medicinal product, dietary supplement or food. It is not intended for use on humans or animals. Sales only to registered research units and laboratories.

GW-0742 (GW0742, trade name “GW 2.0”) is a synthetic small organic molecule of a selective PPARδ agonist — nuclear receptor peroxisome proliferator-activated receptor delta. The substance was created in laboratories GlaxoSmithKline in the early 2000s as a tool for studying the pharmacology of PPAR receptors; the classic publication characterizing the compound is Sznaidman et al. 2003 (Bioorg Med Chem Lett), describing a series of thiazole PPARδ agonists with high affinity and unprecedented selectivity.

GW-0742 binds PPARδ with affinity at the nanomolar level (~1 nM) and over a thousandfold selectivity for PPARα and PPARγ isoforms. In a chemical context, GW-0742 belongs to a class low molecular weight thiazole ligands in the pharmacology of nuclear receptors – this is an important distinction between peptides (BPC-157, TB-500, MOTS-c) and non-steroidal SARMs (RAD-140).

The central axis of the mechanism is the transcription network PPARδ–RXR, one of the best described regulators of fatty acid β-oxidation and adaptation of skeletal muscle to endurance exercise. For this reason, PPARδ agonists – along with GW-501516 (Cardarine) – have been treated in the literature as model “exercise mimetics” for over a decade. The trade name “GW 2.0” signals the positioning of GW-0742 as a compound next generation against GW-501516 (Cardarine) — the first widely described PPARδ agonist.

However, it should be clarified immediately: GW-0742 and GW-501516 are two structurally distinct molecules (different thiazole core, different substituents), not two varieties of the same substance. GW-0742 has higher receptor selectivity for PPARδ; “2.0” refers to an iteration within a class, not an improved version of a single molecule. This reagent is supplied in a 60 capsules of 10 mg GW-0742 — a form adapted to chronic exposure protocols in in vivo models on rodents and to standardize weighings in long-term experiments on exercise metabolism. Purity verified by HPLC ≥98%, identity confirmed by mass spectrometry, COA available for each batch.

Regulatory status

GW-0742 has not completed any phase of human clinical trials with resultant registration. GSK programs (Phase I/II) were discontinued at the preclinical/early clinical stage due to oncological concerns – PPARδ agonists were associated with cell proliferation and carcinogenic signals in long-term rodent studies. No registration as a drug with the EMA, FDA or anywhere in the world.

Not authorized by EFSA as an ingredient of a dietary supplement. PPARδ agonists have been on the WADA Prohibited List (category S4.4, Metabolic Modulators) since 2009 – a substance permanently prohibited in sports. Marketing the product as a “fat burner”, “endurance enhancer for athletes” or “improved Cardarine” is contrary to the Research Use Only framework.

Peroxisome Proliferator-Activated Receptors (PPARα, PPARβ/δ, PPARγ) are a family of ligand-activated nuclear receptors that act as transcription factors dependent on fatty acids and their derivatives. After binding the ligand, PPAR forms a heterodimer with the retinoid X receptor (RXR), and binds to DNA regulatory sequences called PPRE (Peroxisome Proliferator Response Element) and modulates the transcription of lipid and glucose metabolism genes. The three isoforms differ in tissue distribution and gene program:

• PPARα (NR1C1) — dominant in the liver, heart muscle, brown adipose tissue; regulates hepatic β-oxidation and ketogenesis; molecular target of fibrates
• PPARγ (NR1C3) — dominant in adipose tissue; regulates adipogenesis and insulin sensitivity; molecular target of thiazolidinediones (glitazones)
• PPARβ/δ (NR1C2) — expressed widely, with high expression in skeletal muscles, heart and tissues with high energy demand; regulates fatty acid oxidation, thermogenesis and muscle energy metabolism

That’s it PPARδ has become the subject of particular interest in exercise pharmacology. Activation of this isoform in skeletal muscle triggers a transcriptional program similar to the adaptation of endurance training: intensification of β-oxidation of fatty acids, shift of the muscle fiber profile towards oxidation (type I) and metabolic remodeling towards lipid oxidation as the preferred energy substrate. Classic work Narkar et al. 2008 (Cell) solidified the concept that PPARδ agonists—particularly in synergy with AMPK activation—act as “exercise mimetics” in a mouse model. The biological functions of PPARδ include gene expression programs of fundamental importance for energy metabolism:

• β-oxidation of fatty acids — induction of CPT1, MCAD, ACOX1 genes responsible for the transport and oxidation of lipids in the mitochondrial matrix
• Modulation of muscle fiber type — shift of the profile towards type I fibers (oxidative, slow-twitch, endurance)
• Thermogenesis and energy expenditure — modulation of energy dissipation programs in muscle and fat tissue
• Glucose metabolism — influence on the expression of the GLUT4 transporter and insulin sensitivity of peripheral tissues
• Inflammatory modulation — inhibition of the NF-κB pathway in endothelial cells and macrophages

For this reason, pharmacological activation of PPARδ has for years been treated as an interesting target in the search for molecules that modulate the metabolic program of exercise – i.e. classic “exercise mimetics”. Within the Pro-Body offer, the mechanistically adjacent directions are SARMs for fat burning, studied in the paradigm of metabolic remodeling and lipid oxidation.

Chemically, GW-0742 is a synthetic small organic molecule based on a thiazole core, designed for affinity for the PPARδ receptor ligand pocket.

• Common name: GW-0742, GW0742
• Trade name: GW 2.0
• Pharmacological class: selective low molecular weight PPARδ agonist
• Laboratory of Origin: GlaxoSmithKline (early 2000s)
• Molecular type: small organic molecule, thiazole ligand (NOT a peptide, NOT a steroid)
• Delivered form: HPMC hard capsule (vegan), 10 mg of active substance per capsule, 60 capsules; pharmaceutical grade ≥98% HPLC

Table of physicochemical characteristics

GW-0742 binds to the ligand-binding domain of the PPARδ receptor with nanomolar affinity. Binding of the molecule stabilizes the receptor conformation activating heterodimerization with RXR and recruitment of transcriptional coactivators, which leads to increased transcription of target genes on PPRE elements. The mechanism breaks down into six related axes observed in preclinical models. Pharmacological profile observed in preclinical models:

1. PPARδ receptor agonism (nuclear axis) — GW-0742 binds the ligand-binding domain of PPARδ, the receptor couples to RXR and binds PPRE in the promoters of target genes. This is the primary molecular event that initiates the entire transcriptional program; high selectivity for α and γ isoforms makes GW-0742 a valuable tool for the isolated study of the PPARδ axis
2. Induction of fatty acid β-oxidation genes — activation of PPARδ increases the expression of lipid transport and oxidation genes (CPT1 – carnitine-palmitoyltransferase 1, MCAD – medium-chain acyl-CoA dehydrogenase, ACOX1 – acyl-CoA oxidase). This profile shifts muscle metabolism towards lipid oxidation – a phenotype characteristic of endurance training (“exercise mimetic”).
3. Muscle fiber type conversion (type II → type I) — in mouse models, PPARδ activation is associated with a shift in the profile of skeletal fibers towards oxidative, slow-twitch fibers (type I), in accordance with the adaptive program of endurance exercise and endurance phenotype
4. Synergy with AMPK — work by Narkar et al. 2008 (Cell) showed that PPARδ agonists and AMPK activators act complementarily as “exercise mimetics”; AMPK phosphorylates coactivators and PPARδ, enhancing the transcription of oxidative genes. Combined activation of both pathways replicated a greater proportion of the biochemical endurance phenotype in a mouse model than either pathway alone.
5. Anti-inflammatory effect (NF-κB axis) — in endothelial cells and macrophages, activation of PPARδ by GW-501516 and GW-0742 inhibits the NF-κB pathway, reducing the expression of pro-inflammatory cytokines (Coll et al. 2010); an effect studied in the context of vascular and metabolic protection
6. Modulation of glucose metabolism — activation of PPARδ affects the expression of the glucose transporter GLUT4 and improves the insulin sensitivity of peripheral tissues in metabolic models (Lee et al. 2006), which makes GW-0742 a tool in research on metabolic syndrome and insulin resistance

Pharmacokinetic profile (based on preclinical models):

• Oral bioavailability in humans: unknown (data limited to animal models)
• Human PK profile: uncharacterized – no completed phase I studies with resultant registration
• Molecular target: PPARδ ligand-binding domain, heterodimer with RXR, PPRE binding

The PPARδ mechanism activates one axis from many components of the body’s response to physical exercise. Endurance training simultaneously affects the cardiovascular system, skeletal system, central nervous system, hormonal balance and inflammatory profile. Pharmacological activation of PPARδ replicates a portion of the skeletal muscle metabolic program—primarily the lipid oxidation axis—and nothing else. GW-0742 in the “exercise mimetics” class – pharmacological item: In the last decade, several classes of molecules have been designated “exercise mimetics” – differing in their mechanism, research status and evidence profile:

GW-0742 stands out in this group high receptor selectivity towards PPARδ (>1000× relative to α and γ isoforms) and directly targeting the fatty acid β-oxidation transcriptional machinery – as opposed to uncouplers (uncoupling already existing mitochondria) and ERR pan-agonists such as SLU-PP-332, which target mitochondrial biogenesis through a neighboring node of the metabolic network. The mechanistic predecessor of the GW-0742 in this class is Cardarine GW-501516 — the first generation of PPARδ agonists, with which GW-0742 is sometimes compared in comparative analyzes of receptor selectivity and β-oxidation.

GW-0742 is used in research in several areas of nuclear receptor pharmacology and exercise metabolism. In in vivo models (mouse, rat), its impact on the expression of β-oxidation genes (CPT1, MCAD, ACOX1), muscle fiber profile, running endurance parameters (treadmill tests), lipid profile and inflammatory markers are examined. In vitro models (C2C12 muscle cell lines, hepatocyte cultures, endothelial cells) measure OCR and ECAR on Seahorse-type platforms, kinetics of PPRE target gene expression, and structure-activity relationship (SAR) analyzes of selective PPARδ ligands. Specific research directions include:

• Pharmacological studies on PPARδ as a therapeutic target — characterization of selective ligands, mapping of the agonist profile against PPAR isoforms, SAR analyzes and receptor selectivity; GW-0742 as a reference highly selective PPARδ agonist
• Models of muscle metabolism and endurance — treadmill tests, indirect calorimetry, fiber type analysis, oxidative gene expression in rodent skeletal muscle
• Experiments on “exercise mimetics” — comparative pharmacological studies in the paradigm of endurance, β-oxidation and synergy with AMPK (continuation of the research line of Narkar et al. 2008)
• Research on metabolic syndrome and insulin resistance — modulation of GLUT4, insulin sensitivity and lipid profile in metabolic models
• Cardioprotective and anti-inflammatory studies — modulation of the NF-κB pathway in endothelial cells, protection of cardiomyoblasts in stress models (Pesant et al. 2006; Coll et al. 2010)

In comparative comparisons of metabolic modulators, GW-0742 is sometimes compared with Rev-ErbA axis agonists, such as SR-9011, tested for their impact on energy metabolism and substrate oxidation – a different molecular node, a similar area of ​​research interest.

GW-0742 (GW 2.0; 10 mg × 60 capsules) is a synthetic small organic molecule of the selective PPARδ agonist class from GlaxoSmithKline laboratories (Sznaidman et al. 2003), binding the receptor with nanomolar affinity (~1 nM) and selectivity >1000× towards PPARα isoforms and PPARγ. In preclinical models, the compound is characterized as an “exercise mimetic” – it increases β-oxidation of fatty acids (CPT1, MCAD, ACOX1), shifts the profile of muscle fibers towards oxidation (type I) and works in synergy with AMPK (Narkar et al. 2008).

GW-0742 is a separate molecule from GW-501516 (Cardarine), not a variant of it; both share the oncological risk profile from long-term rodent studies. HPLC purity ≥98%, MS confirmation (Q-TOF), COA for each batch. Regulatory Status – Research Use Only; GSK clinical programs suspended; PPARδ agonists permanently banned by WADA (category S4.4) since 2009.

1. Sznaidman ML, Haffner CD, Maloney PR, Fivush A, Chao E, Goreham D, et al. (2003). Novel selective small molecule agonists for peroxisome proliferator-activated receptor delta (PPARδ) — synthesis and biological activity. PubMed
2. Narkar VA, Downes M, Yu RT, Embler E, Wang YX, Banayo E, et al. (2008). AMPK and PPARδ agonists are exercise mimetics. PubMed
3. Coll T, Barroso E, Álvarez-Guardia D, Serrano L, Salvadó L, Merlos M, et al. (2010). Activation of peroxisome proliferator-activated receptor-δ by GW501516 prevents fatty acid-induced nuclear factor-κB activation and insulin resistance in skeletal muscle cells. PubMed
4. Pesant M, Sueur S, Dutartre P, Tallandier M, Grimaldi PA, Rochette L, et al. (2006). Peroxisome proliferator-activated receptor δ (PPARδ) activation protects H9c2 cardiomyoblasts from oxidative stress-induced apoptosis. PubMed
5. Lee CH, Olson P, Hevener A, Mehl I, Chong LW, Olefsky JM, et al. (2006). PPARδ regulates glucose metabolism and insulin sensitivity. PubMed