CAY10580

CAY10580 is a potent and selective prostaglandin EP4 receptor agonist (Ki=35 nM)[1].

Signaling Pathways >> GPCR/G Protein >> Prostaglandin Receptor

Research Areas >> Metabolic Disease

EP4:35 nM (Ki)

EP4 Receptor:35 nM (Ki)

EP2 Receptor:3000 nM (Ki)

EP3 receptor:2000 nM (Ki)

CAY10580 (10-10000 nM; 40 min) significantly increases apical membrane abundance of AQP2 in MDCK cells at 100 to 10000 nM[2].

CAY10580 (200 μg/kg body weight; i.p; daily for three weeks) effectively prevents diet-induced hypercholesterolemia, enhances endogenous bile acid synthesis and their fecal excretion[3]. Animal Model: Six-week old male EP4+/+ mice (Treating high fat diet-challenged mice)[3] Dosage: 200 μg/kg body weight Administration: Intraperitoneal injection; daily for remaining three weeks Result: High fat diet fed mice exhibited lower total cholesterol levels compared to the vehicle group by 28.5%. Total cholesterol levels decreased from 137.4 to 98.2 mg/dl, restoring plasma cholesterol back to near-normal values.

[1]. Billot X, et al. Discovery of a potent and selective agonist of the prostaglandin EP4 receptor. Bioorg Med Chem Lett. 2003;13(6):1129-1132.

[2]. Olesen ET, et al. Vasopressin-independent targeting of aquaporin-2 by selective E-prostanoid receptor agonists alleviates nephrogenic diabetes insipidus. Proc Natl Acad Sci U S A. 2011;108(31):12949-12954.

[3]. Ying F, et al. EP4 emerges as a novel regulator of bile acid synthesis and its activation protects against hypercholesterolemia. Biochim Biophys Acta Mol Cell Biol Lipids. 2018;1863(9):1029-1040.