GW0742 powder, also known as GW610742 powder and GW0742X is a PPARδ/β agonist. GW0742 Induces Early Neuronal Maturation of Cortical Post-Mitotic Neurons. GW0742 prevents hypertension, vascular inflammatory and oxidative status, andendothelial dysfunction in diet-induced obesity. GW0742 has direct protective effects on right heart hypertrophy.GW0742 may enhance lipid metabolism in heart both in vivo and in vitro.
02 GW0742 (GW610742) powder video
03 GW0742 (GW610742) Base Information
|Name||GW0742 (GW610742) powder|
|Chemical name||GW0742; GW-0742; GW 0742; GW0742X; GW-0742X; GW 0742X; GW610742; GW-610742; GW 610742.|
|Synonyms||[4-[[[2-[3-fluoro-4-(trifluoromethyl)phenyl]-4-methyl-5-thiazolyl]methyl]thio]-2-methyl phenoxy]-acetic acid|
|Molecular Weight||471.4846 g/mol|
|Appearance||White to Off-white|
|Half Life||14 days|
|Solubility||Soluble in DMSO, not in water|
|Storage Condition||0 – 4 C for short term (days to weeks), or -20 C for long term (months).|
|Application||GW0742 (also known as GW610742) is a PPARδ/β agonist that is investigated for drug use by GlaxoSmithKline.|
04 GW0742 (GW610742) General Description
GW0742 powder is a selective PPARδ agonist (EC50 = 1.1 nM) that exhibits 1,000-fold selectivity over the other human PPAR subtypes. GW0742 exhibits time-dependent neuroprotection in low KCl-induced apoptosis in cerebellar granule neuronal cultures. Despite the neuroprotective properties observed, prolonged (48h) incubation with GW0742 produced significant inherent toxicity. This celldeath was determined to be apoptotic as identified with the TUNEL assay.
05 GW0742 (GW610742) powder History
The development of new drugs for the treatment of diabetes mellitus (DM) iscritically important. Insulin resistance (IR) is one of the main problems associated with type-2 DM (T2DM) seen in clinics. GW0742 powder, a selective peroxisomeproliferator-activated receptor (PPAR)-δ agonist, has been shown to ameliorate metabolic abnormalities including IR in skeletal muscle in mice fed high-fructose corn syrup. However, the influence of GW0742 on systemic insulin sensitivity has still not been elucidated. Therefore, it is important to investigate the effect of GW0742 on systemic IR in diabetic rats for the development of new drugs.
06 GW0742 (GW610742) Mechanism Of Action
A high throughput screening campaign was conducted to identify small molecules with the ability to inhibit the interaction between the vitamin D receptor(VDR) and steroid receptor coactivator 2. These inhibitors represent novel molecular probes to modulate gene regulation mediated by VDR. The peroxisomeproliferator-activated receptor δ (PPARδ) agonist GW0742 was among the identified VDR-coactivator inhibitors and has been characterized herein as a pannuclear receptor antagonist at concentrations higher than 12.1 µM. The highest antagonist activity for GW0742 was found for VDR and the androgen receptor (AR). Surprisingly, GW0742 behaved as PPAR agonist/antagonist activating transcription at lower concentration and inhibiting this effect at higher concentrations. A unique spectroscopic property of GW0742 was identified as well. Inthe presence of rhodamine-derived molecules, GW0742+ increased fluorescence intensity and fluorescence polarization at an excitation wavelength of 595 nm and emission wavelength of 615 nm in a dose dependent manner. The GW0742-inhibited NR-coactivator binding resulted in a reduced expression of five different NR target genes in LNCaP cells in the presence of agonist. Especially VDR target genes CYP24A1, IGFBP-3 and TRPV6 were negatively regulated by GW0742. GW0742 is the first VDR ligand inhibitor lacking the secosteroid structure of VDR ligand antagonists. Nevertheless, the VDR-meditated downstream process of cell differentiation was antagonized by GW0742 in HL-60 cells that were pretreated with the endogenous VDR agonist 1,25-dihydroxyvitamin D3.
07 GW0742 (GW610742) Application
GW0742 prevents hypertension, vascular inflammatory and oxidative status, andendothelial dysfunction in diet-induced obesity. GW0742 has direct protectiveeffects on right heart hypertrophy.GW0742 may enhance lipid metabolism in heart both in vivo and in vitro.
08 GW0742 (GW610742) More research
GW0742 attenuated the increased HOMA-IR in diabetic rats fed a fructose-richdiet. This action was blocked by GSK0660 at the dose sufficient to inhibit PPAR-δ. Improvement of IR by GW0742 was also characterized in diabetic rats using hyperinsulinemic euglycemic clamping. Additionally, an increase of insulinsensitivity due to GW0742 was observed in these diabetic rats. Moreover, GW0742 reduced the hyperglycemia in T1DM rats lacking insulin. Western blotting analysis indicated that GW0742 reversed the decrease in GLUT4 and markedly reduced the increased PEPCK in liver.
09 GW0742 (GW610742) Document Download
10 GW0742 (GW610742) Reference
- 01. Overview
- 02. GW0742 (GW610742) powder video
- 03. GW0742 (GW610742) Base Information
- 04. GW0742 (GW610742) General Description
- 05. GW0742 (GW610742) powder History
- 06. GW0742 (GW610742) Mechanism Of Action
- 07. GW0742 (GW610742) Application
- 08. GW0742 (GW610742) More research
- 09. GW0742 (GW610742) Document Download
- 10. GW0742 (GW610742) Reference