Gefapixant is the approved generic name for a compound also known as MK-7264, and prior to that AF-219 and RO-4926219. It is the first-in-class clinically developed antagonist for the P2X3 subtype of trimeric ionotropic purinergic receptors, a family of ATP-gated excitatory ion channels, showing nanomolar potency for the human P2X3 homotrimeric channel and essentially no activity at related channels devoid of P2X3 subunits. As the first P2X3 antagonist to have progressed into clinical studies it has now progressed to the point of successful completion of Phase 3 investigations for the treatment of cough, and the NDA application is under review with US FDA for treatment of refractory chronic cough or unexplained chronic cough. The molecule was discovered in the laboratories of Roche Pharmaceuticals in Palo Alto, California, but clinical development then continued with the formation of Afferent Pharmaceuticals for the purpose of identifying the optimal therapeutic indication for this novel mechanism and establishing a clinical plan for development in the optimal patient populations selected. Geoff Burnstock was a close collaborator and advisor to the P2X3 program for close to two decades of discovery and development. Progression of gefapixant through later stage clinical studies has been conducted by the research laboratories of Merck & Co., Inc., Kenilworth, NJ, USA (MRL; following acquisition of Afferent in 2016), who may commercialize the product once authorization has been granted by regulatory authorities.

Gefapixant 是一种化合物的批准通用名称，也称为 MK-7264，在 AF-219 和 RO-4926219 之前。它是首个临床开发的三聚离子型嘌呤能受体 P2X3 亚型拮抗剂，这是一个 ATP 门控兴奋性离子通道家族，对人类 P2X3 同三聚体通道显示纳摩尔级效力，并且在没有 P2X3 的相关通道上基本上没有活性亚基。作为第一个进入临床研究的 P2X3 拮抗剂，目前已成功完成治疗咳嗽的 3 期研究，美国 FDA 正在审查 NDA 申请，用于治疗难治性慢性咳嗽或不明原因的慢性咳嗽。咳嗽。该分子是在加利福尼亚州帕洛阿尔托的罗氏制药实验室中发现的，但随后临床开发随着 Afferent Pharmaceuticals 的形成而继续，目的是确定这种新机制的最佳治疗适应症，并为选定的最佳患者群体制定临床开发计划。杰夫·伯恩斯托克 (Geoff Burnstock) 是 P2X3 计划的密切合作者和顾问，从事近二十年的发现和开发。美国新泽西州凯尼尔沃思默克公司（MRL；2016 年收购 Afferent 后）的研究实验室已通过后期临床研究推进吉法吡酯，一旦获得授权，他们可能会将产品商业化由监管机构。