AF-353 (hydrochloride)

AF-353 is a noncompetitive dual antagonist of the purinoreceptors P2X₃ and P2X_2/3 (IC₅₀s = 10 and 79.4 nM, respectively).^1,2 It is selective for P2X₃ and P2X_2/3 over P2X₁, P2X₂, P2X₄, P2X₅, and P2X₇ (IC₅₀ = >10 µM for all).² It inhibits calcium flux in CHO-K1 cells expressing the rat P2X₃ receptor and in 1321N1 cells expressing the human P2X₃ and P2X_2/3 receptors (IC₅₀s = 8.91, 8.71, and 38.9 nM, respectively). AF-353 decreases the electrical signals in the detrusor, but not striated, muscle of the bladder in female rats.³

1.Carter, D.S., Alam, M., Cai, H., et al.Identification and SAR of novel diaminopyrimidines. Part 1: The discovery of RO-4, a dual P2X3/P2X2/3 antagonist for the treatment of painBioorg. Med. Chem. Lett.19(6)1628-1631(2009) 2.Gever, J.R., Soto, R., Henningsen, R.A., et al.AF-353, a novel, potent and orally bioavailable P2X3/P2X2/3 receptor antagonistBr. J. Pharmacol.160(6)1387-1398(2010) 3.Salazar, B.H., Hoffman, K.A., Zhang, C., et al.Electrical activity of the bladder Is attenuated by intravesical inhibition of P2X2/3 receptors during micturition in female ratsInt. Neurourol. J.21(4)259-269(2017)