Description
Prostaglandin E2 (PGE2) exerts its effects through four separate G coupled-protein receptors (EP1-4). L-161,982 is a potent and selective EP4 receptor antagonist. It demonstrates selective binding to human EP4 receptors with a Ki value of 0.024 μM compared to other receptors of the prostanoid family, EP1, EP2, EP3, DP, FP, and IP, with Ki values of 17, 23, 1.9, 5.1, 5.6, and 6.7 μM, respectively. L-161,982 at 10 mg/kg/day suppresses PGE2-stimulated bone formation in young rats and at 100 nM reverses the anti-inflammatory action of PGE2 in LPS-activated human macrophages. At 10 μM L-161982 blocks PGE2-induced cell proliferation in HCA-7 colon cancer cells.
Uses
L-161,982 is an EP4 receptor antagonist, which blocks prostaglandin E2-induced signal transduction and cell proliferation in HCA-7 colon cancer cells.
Definition
ChEBI: N-[2-[4-[[3-butyl-5-oxo-1-[2-(trifluoromethyl)phenyl]-1,2,4-triazol-4-yl]methyl]phenyl]phenyl]sulfonyl-3-methyl-2-thiophenecarboxamide is a member of biphenyls.
Biological Activity
EP 4 receptor antagonist that is selective over all other members of the prostanoid receptor family (K i values are 0.024, 0.71, 1.90, 5.10, 5.63, 6.74, 19 and 23 μ M for human EP 4 , TP, EP 3 , DP, FP, IP, EP 1 and EP 2 receptors respectively). Suppresses PGE 2 -induced bone formation in rats and prevents the nociceptive response induced by misoprostol in formalin-injected mice.
Biochem/physiol Actions
L-161,982 is a potent EP4 receptor antagonist that is selective over all other members of the prostanoid receptor family (Ki values are 0.024, 0.71, 1.90, 5.10, 5.63, 6.74, 19 and 23 μM for human EP4, TP, EP3, DP, FP, IP, EP1 and EP2 receptors respectively.
References
[1] M. MACHWATE. Prostaglandin receptor EP(4) mediates the bone anabolic effects of PGE(2).[J]. Molecular Pharmacology, 2001, 60 1 1: 36-41. DOI:
10.1124/mol.60.1.36[2] KIYOSHI TAKAYAMA. Prostaglandin E2 suppresses chemokine production in human macrophages through the EP4 receptor.[J]. The Journal of Biological Chemistry, 2002, 277 46: 44147-44154. DOI:
10.1074/jbc.m204810200[3] DURGA PRASAD CHERUKURI . The EP4 receptor antagonist, L-161,982, blocks prostaglandin E2-induced signal transduction and cell proliferation in HCA-7 colon cancer cells[J]. Experimental cell research, 2007, 313 14: Pages 2969-2979. DOI:
10.1016/j.yexcr.2007.06.004[4] ANG LIN. TLR4 signaling promotes a COX-2/PGE2/STAT3 positive feedback loop in hepatocellular carcinoma (HCC) cells[J]. Oncoimmunology, 2015, 5 1. DOI:
10.1080/2162402x.2015.1074376
