GSK726701A

GSK726701A is a novel prostaglandin E2 receptor 4 (EP4) partial agonist with a pEC₅₀ of 7.4. IC50 & Target: pEC50: 7.4^[1] In Vitro: 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]. In Vivo: 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].