GSK726701A

GSK726701A is a novel prostaglandin E2 receptor 4 (EP4) partial agonist with a pEC50 of 7.4.

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

Research Areas >> Inflammation/Immunology

Research Areas >> Neurological Disease

pEC50: 7.4[1]

GSK726701A has high selectivity (>100-fold) against a set of other prostaglandin receptors (EP1-3 , DP1 , FP, IP, TP) and no significant activity against a wider panel of targets. It demonstrates EP4 agonist activity with similar potency and intrinsic activity (pEC50=8.2) in a human whole blood (HWB) assay on the inhibition of LPS-mediated TNFα induction[1].

GSK726701A has good pharmacokinetic file in rat, dog and monkey. GSK726701A has robust activity in a range of animal models of inflammatory and neuropathic pain GSK726701A demonstrates a time-dependant, full reversal of CCI-induced mechanical allodynia at 3mg/kg, equivalent to the clinical gold standard gabapentin (30mg/kg). GSK726701A has an ED50 of 0.2mg/kg in the FCA acute rat model of inflammatory pain[1].

Rats[1] The effect of GSK726701A (0.03-1mg/kg p.o. b.i.d. x5 days) is investigated on the FCA acute rat model of inflammatory pain[1].

[1]. Healy MP, et al. Discovery of {4-[4,9-bis(ethyloxy)-1-oxo-1,3-dihydro-2H-benzo[f]isoindol-2-yl]-2-fluorophenyl}acetic acid (GSK726701A), a novel EP4 receptor partial agonist for the treatment of pain. Bioorg Med Chem Lett. 2018 Jun 1;28(10):1892-1896.

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