Gefapixant (AF219; MK-7264)

Description: Gefapixant (also known as AF-219 and MK-7264) is a novel, potent, and orally bioactive P2X3 receptor (P2X3R) antagonist with IC50s of ca.30 nM versus recombinant hP2X3 homotrimers and 100-250 nM at hP2X2/3 heterotrimeric receptors. Treating pain by inhibiting ATP activation of P2X3-containing receptors heralds an exciting new approach to pain management, and Afferent's program marks the vanguard in a new class of drugs poised to explore this approach to meet the significant unmet needs in pain management. P2X3 receptor subunits are expressed predominately and selectively in so-called C- and Adelta-fiber primary afferent neurons in most tissues and organ systems, including skin, joints, and hollow organs, suggesting a high degree of specificity to the pain sensing system in the human body. P2X3 antagonists block the activation of these fibers by ATP and stand to offer an alternative approach to the management of pain and discomfort.

References: Front Cell Neurosci. 2013; 7: 267.; Purinergic Signal. 2012 Feb; 8(Suppl 1):3-26.