GSK-269984A

GSK-269984A is a Prostaglandin E2 Receptor 1 (EP1) antagonist with a pIC50 of 7.9.

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

Research Areas >> Neurological Disease

EP1 Receptor:7.9 (pIC50)

Results from [3H]-PGE2 binding assay in CHO cells overexpressing the human EP1 receptor demonstrate that GSK-269984A is an antagonist of EP1 receptor with a pIC50 of 7.9. GSK-269984A is found to cause a concentration-dependent rightward shift of the PGE2 dose-response curve and Schild analysis shows that GSK-269984A is a competitive antagonist with pA2 8.1±0.3 and slope 1.0[1].

GSK-269984A demonstrates an ED50 of 2.6 mg/kg (po), with the 10 mg/kg dose showing equivalent reversal of hypersensitivity to the standard. GSK-269984A displays moderate blood clearance in the ratand dog and high clearance in the monkey which is reflected in the half-life for each species[1].

Rats are used in this study. GSK-269984A is progressed to the rat CFA model of inflammatory pain. GSK-269984A is dosed orally at doses of 1, 3 and 10 mg/kg, 23 h after intraplantar administration of the adjuvant. Analgesia is assessed 1 h post-dose of GSK-269984A[1].

[1]. Hall A, et al. Discovery of sodium 6-[(5-chloro-2-{[(4-chloro-2-fluorophenyl)methyl]oxy}phenyl)methyl]-2-pyridinecarboxylate (GSK269984A) an EP(1) receptor antagonist for the treatment of inflammatory pain. Bioorg Med Chem Lett. 2009 May 1;19(9):2599-603.

Dinoprostone | Prostaglandin E1 | E7046 | ONO-AE3-208 | PF 04418948 | Fevipiprant | grapiprant | TG6-10-1 | Taprenepag | GW 627368 | MRE-269 | Ramatroban | AH 6809 | Laropiprant | AZD1981