tcsc0021727 Gefapixant

Gefapixant is an orally active P2X3 receptor (P2X3R) antagonist with IC ₅₀s of ~30 nM versus recombinant hP2X3 homotrimers and 100-250 nM at hP2X2/3 heterotrimeric receptors.

IC50 & Target: IC50: ~30 nM (recombinant hP2X3 homotrimers), 100-250 nM (hP2X2/3 heterotrimeric receptors)^[1].

In Vitro: The aryloxy-pyrimidinediamine, Gefapixant (AF-219) is an orally active small molecule antagonist at human P2X3-containing receptors. The IC₅₀ of Gefapixant has been reported as ~30 nM versus recombinant hP2X3 homotrimers and 100-250 nM at hP2X2/3 heterotrimeric receptors, potencies very similar to those reported for recombinant rat receptors, and it displays no inhibitory impact on any non-P2X3 subunit containing receptors (IC₅₀ values>>10,000 nM at recombinant homotrimeric hP2X1, hP2X2, hP2X4, rP2X5 and hP2X7 channels)^[1].

In Vivo: In an adjuvant-induced rthritis model in rat (7d following intraplantar administration of complete Freund's adjuvant), AF-353 produces dose-dependent antihyperalgesia in weight-bearing asymmetry and von Frey filament mechanical tests; magnitude of effect is compared with that of the NSAID naproxen. In a rat model of knee osteoarthritis (14d following intra-articular administration of monoiodoacetate), Gefapixant (7d bid, orally; right) attenuates the weight bearing laterality with complete reversal of apparent hyperalgesia at the two higher doses^[2].