GW501516

Biological Activity

GW501516 (GSK-516, GW1516) is a potent and highly selective PPARβ/δ agonist, with EC50 of 1 nM, with 1000-fold selectivity over hPPARα and hPPARγ. The PPARβ/δ agonist GW501516 inhibited the increase caused by TNF-α in the mRNA levels of the NF-κB target genes interleukin 8 (IL-8), TNF-α and thymic stromal lymphopoietin (TSLP). GW501516 exhibited agonist effects with EC(50) values of 560 and 55 nM against PPARα and PPARδ, respectively, in a luciferase assay. Moreover, GW501516 also exhibited potent ability to induce oleic acid oxidation in a human myotube cell assay with EC(50)=3.7 nM. In contrast, GW501516 treatment decreased TNF-α-induced p65 acetylation. GW501516 increased AMPK phosphorylation and the subsequent p300 phosphorylation, leading to a marked reduction in the association between p65 and this transcriptional co-activator.

Customer Product Validations & Biological Datas

	Source	Oncotarget (2017). Figure 1. GW501516
	Method	migration assay
	Cell Lines	MDA-MB-231, MDA-MB-435, and ZR-75-1 cells
	Concentrations	100 nM
	Incubation Time	48 h
	Results	Consistent with the results in MDA-MB-231 cells, the migration of other high metastatic human breast cancer cell lines MDA-MB-435 and ZR-75-1 was dose-dependently inhibited in the presence of GW501516

Chemical Information

Molecular Weight	453.5
Formula	C21H18F3NO3S2
CAS Number	317318-70-0
Solubility (25°C)	DMSO 47 mg/mL
Storage	Powder          -20°C   3 years ;  4°C   2 years In solvent       -80°C   6 months ;  -20°C   1 month

Conversion of different model animals based on BSA (PMID: 27057123)

Species	Mouse	Rat	Rabbit	Guinea pig	Hamster	Dog
Weight (kg)	0.02	0.15	1.8	0.4	0.08	10
Body Surface Area (m2)	0.007	0.025	0.15	0.05	0.02	0.5
Km factor	3	6	12	8	5	20

Animal A (mg/kg) = Animal B (mg/kg) multiplied by	Animal B Km
	Animal A Km

For example, to modify the dose of Compound A used for a mouse (20 mg/kg) to a dose based on the BSA for a rat, multiply 20 mg/kg by the K_m factor for a mouse and then divide by the K_m factor for a rat. This calculation results in a rat equivalent dose for Compound A of 10 mg/kg.

References

[1] Lu T, et al. Diabetes. Reactive oxygen species signaling facilitates FOXO-3a/FBXO-dependent vascular BK channel β1 subunit degradation in diabetic mice.

[2] Iwaisako K, et al. Proc Natl Acad Sci U S A. Protection from liver fibrosis by a peroxisome proliferator-activated receptor δ agonist.

[3] Ciocoiu CC, et al. Bioorg Med Chem. Synthesis, molecular modeling studies and biological evaluation of fluorine substituted analogs of GW 501516.

[4] Barroso E, et al. Biochem Pharmacol. The peroxisome proliferator-activated receptor β/δ (PPARβ/δ) agonist GW501516 prevents TNF-α-induced NF-κB activation in human HaCaT cells by reducing p65 acetylation through AMPK and SIRT1.