Purity: > 98%
|IUPAC Name:||2-[2-methyl-4-[[4-methyl-2-[4-(trifluoromethyl)phenyl]-1,3-thiazol-5-yl]methylsulfanyl]phenoxy]acetic acid|
GW501516(CAS 317318-70-0), also known as Endurobol or GSK-516 ,is a PPARδ receptor agonist. Endurobol was entered into clinical development as a drug candidate for metabolic diseases and cardiovascular diseases, and was abandoned in 2007 because animal testing showed that the drug caused cancer to develop rapidly in several organs.
GW501516 is peroxisome proliferator-activated receptor delta agonist. The Phase-II clinical trials in Hyperlipidaemia in USA started in 2003.
1. Bioorg Med Chem. 2011 Dec 1;19(23):6982-8. doi: 10.1016/j.bmc.2011.10.020. Epub 2011 Oct 17.
Synthesis, molecular modeling studies and biological evaluation of fluorine substituted analogs of GW 501516.
Ciocoiu CC(1), Ravna AW, Sylte I, Rustan AC, Hansen TV.
(1)School of Pharmacy, Department of Pharmaceutical Chemistry, University of Oslo, PO BOX 1068, Blindern, N-0316 Oslo, Norway.
(±)-2-Fluoro-2-(2-methyl-4-(((4-methyl-2-(4-(trifluoromethyl)phenyl)thiazol-5-yl) methyl)thio)phenoxy)acetic acid (2a) has been prepared and subjected to biological testing against all three subtypes of the PPARs. This compound exhibited agonist effects with EC(50) values of 560 and 55 nM against PPARα and PPARδ, respectively, in a luciferase assay. Moreover, compound (±)-2a also exhibited potent ability to induce oleic acid oxidation in a human myotube cell assay with EC(50)=3.7 nM. Compound (±)-2a can be classified as a dual PPARα/δ agonist with a 10-fold higher potency against the PPARδ receptor than against the PPARα receptor. Molecular modeling studies revealed that both enantiomers of 2a bind to the PPARδ receptor with similar binding energies.
2. Am J Physiol Endocrinol Metab. 2006 Apr;290(4):E607-11. Epub 2005 Nov 8.
PPARdelta activator GW-501516 has no acute effect on glucose transport in skeletal muscle.
Terada S(1), Wicke S, Holloszy JO, Han DH.
(1)Division of Geriatrics and Nutritional Sciences, Department of Medicine, Washington University School of Medicine, St. Louis, Missouri 63110, USA.
It has been reported that treatment of cultured human skeletal muscle myotubes with the peroxisome proliferator-activated receptor-delta (PPARdelta) activator GW-501516 directly stimulates glucose transport and enhances insulin action. Cultured myotubes are minimally responsive to insulin stimulation of glucose transport and are not a good model for studying skeletal muscle glucose transport. The purpose of this study was to evaluate the effect of GW-501516 on glucose transport to determine whether the findings on cultured myotubes have relevance to skeletal muscle. Rat epitrochlearis and soleus muscles were treated for 6 h with 10, 100, or 500 nM GW-501516, followed by measurement of 2-deoxyglucose uptake. GW-501516 had no effect on glucose uptake. There was no effect on insulin sensitivity or responsiveness. Also, in contrast to findings on myotubes, treatment of muscles with GW-501516 did not result in increased phosphorylation or increased expression of AMP-activated protein kinase (AMPK) or p38 mitogen-activated protein kinase (MAPK). Treatment of epitrochlearis muscles with GW-501516 for 24 h induced a threefold increase in uncoupling protein-3 mRNA, providing evidence that the GW-501516 compound that we used gets into and is active in skeletal muscle. In conclusion, our results show that, in contrast to myotubes in culture, skeletal muscle does not respond to GW-501516 with 1) an increase in AMPK or p38 MAPK phosphorylation or expression or 2) direct stimulation of glucose transport or enhanced insulin action.