GW7647 is a potent PPARα agonist, with EC50s of 6 nM, 1.1 μM, and 6.2 μM for human PPARα, PPARγ and PPARδ, respectively.
GW7647 (1 μM) causes a significant increase of PDZK1 protein expression to 129.7 ± 6.5% of vehicle treated control in Caco2BBE cells in the absence and presence of IL-1β. GW7647 also attenuates the IL-1β-mediated decrease in PDZK1 expression[1]. GW7647 (50 nM) stimulates the PI3K phosphorylation followed by the Akt (Ser473) phosphorylation, which induces NOS1 phosphorylation increased the amounts of NO released in the stripped antral mucosa. GW7647 (50 nM) enhances the initial phase of Ca2+-regulated exocytotic events stimulated by ACh in antral mucous cells, but GW7647 alone does not evoke any exocytotic event. GW7647 plus ACh stimulates the effects of wortmannin (50 nM) and AKT-inh (100 nM) on the exocytotic events in antral mucous cells[2]. GW 7647 (100 nM) reduces the AQP9 protein abundance by 43%, but it shows not significant effect at 10 and 1,000 nM in WIF-B9 hepatocytes. GW 7647 (100 nM) causes a 24% reduction in AQP9 protein abundance in HepG2 cells, however, it does not significantly increase the protein abundance of L-FABP in HepG2 hepatocytes[3].
GW7647 (3 mg/kg per day) does not prevent the development of cardiac hypertrophy, but it prevents the decline in left ventricular ejection fraction in vivo[4].
References:
[1]. Luo M, et al. IL-1β-Induced Downregulation of the Multifunctional PDZ Adaptor PDZK1 Is Attenuated by ERK Inhibition, RXRα, or PPARα Stimulation in Enterocytes. Front Physiol. 2017 Feb 7;8:61.
[2]. Tanaka S, et al. PPARα induced NOS1 phosphorylation via PI3K/Akt in guinea pig antral mucous cells: NO-enhancement in Ca(2+)-regulated exocytosis. Biomed Res. 2016;37(3):167-78.
[3]. Lebeck J, et al. Hepatic AQP9 expression in male rats is reduced in response to PPARα agonist treatment. Am J Physiol Gastrointest Liver Physiol. 2015 Feb 1;308(3):G198-205.
[4]. Lam VH, et al. Activating PPARα prevents post-ischemic contractile dysfunction in hypertrophied neonatal hearts. Circ Res. 2015 Jun 19;117(1):41-51.
[5]. Brown PJ, et al. Identification of a subtype selective human PPARalpha agonist through parallel-array synthesis. Bioorg Med Chem Lett. 2001 May 7;11(9):1225-7.