af 353

AF-353 (Ro-4) 是一种选择性、可口服的 P2X3 P2X2 3 受体拮抗剂，抑制人和大鼠 P2X3 的 pIC50值为 8.0，抑制人 P2X2 3 的 pIC50值为 7.3。

This novel compound is an orally bioavailable antagonist of P2X3 P2X2 3 receptors, exhibiting potent activity with a pIC50 of 8 in both human and rat, and a pIC50 of 7.3 specifically for the human P2X2 3 receptor. It demonstrates high brain penetration, evidenced by a brain to plasma ratio of 6, and effectively blocks agonist-evoked intracellular Ca2+ flux and inward currents within the nanomolar range (10 nM to 1 µM) in cell lines that express human P2X3 and P2X2 3 receptors recombinantly. The compound also shows favorable pharmacokinetic properties, with a half-life (t1 2) of 1.63 hours and a time to reach maximum concentration (Tmax) of 30 minutes.