Background:

GSK0660 is a potent antagonist of PPARβ and PPARδ, with IC50s of 155 nM for both isoforms.

GSK0660 is a potent antagonist of PPARβ and PPARδ, with IC50s of both 155 nM, and is nearly inactive on PPARα and PPARγ with IC50s of both >10 μM. GSK0660 antagonizes 100% of the activity of PPARβ/δ with a pIC50 of 6.8. GSK0660 (100 nM) reduces CPT1a (a PPARβ/δ target gene) expression below the basal vehicle-treated level by approximately 50%, but shows no effect on PDK4 expression, which is also a PPARβ/δ target gene in skeletal muscle cells[1]. GSK0660 (0.5 μM) reduces the levels of AMPK and eNOS phosphorylation, and BMP-2, Runx-2 mRNA expression in MC3T3-E1 cells. GSK0660 (0.1 and 0.5 μM) reverses the bezafibrate-induced enchancement of ALP activity on d 7 in MC3T3-E1 cells[2]. GSK0660 (1 μM) markedly blocks GW501516-mediated attenuation of glutamate release, and the effect of GW501516 on ROS generation in BV-2 cells stimulated with LPS. Furthermore, GSK0660 significantly reduces inhibitory effect of GW501516 on the LPS-induced expression of gp91phox mRNA in BV-2 cells[3].

参考文献:
[1]. Shearer BG, et al. Identification and characterization of a selective peroxisome proliferator-activated receptor beta/delta (NR1C2) antagonist. Mol Endocrinol. 2008 Feb;22(2):523-9. Epub 2007 Nov 1.
[2]. Zhong X, et al. Bezafibrate enhances proliferation and differentiation of osteoblastic MC3T3-E1 cells via AMPK and eNOS activation. Acta Pharmacol Sin. 2011 May;32(5):591-600.
[3]. Lee WJ, et al. Activation of PPARδ attenuates neurotoxicity by inhibiting lipopolysaccharide-triggered glutamate release in BV-2 microglial cells. J Cell Biochem. 2018 Feb 1.