BAY-1797 is an orally active and selective P2X4 antagonist (IC50: 211 nM against human P2X4) with anti-nociceptive and anti-inflammatory effects. BAY-1797 displays no or very weak activity on the other P2X ion channels.

P2X7 (human):10.6 μM , P2X23 (human):>30 μM , P2X4 (human):211 nM , P2X1 (human):>50 μM , P2X3 (human):8.3 μM

BAY-1797 inhibits human, mouse, and rat P2X4 in 1321N1 cells (IC50s: 108 nM, 112 nM, and 233 nM). BAY-1797 exerts no measurable activity on hERG and carbonic anhydrase II (both IC50>10 μM). BAY-1797 (10 μM) is also tested against a panel of off-targets, including GPCRs, ion channels, kinases, and transporters. Inhibitory activity against the dopamine transporter (IC50: 2.17 μM) was revealed as the only hit.

BAY-1797 (12.5-50 mg/kg; p.o.) significantly induces PGE2 levels in the inflamed paw in the mouse Complete Freund’s Adjuvant (CFA) inflammatory pain model. At 50 mg/kg daily, BAY-1797 significantly reduces ipsilateral paw load 24 and 48 hours post-CFA injection. Pharmacokinetic parameters include AUCnorm of 1.06 kg h/L, Vss of 3.67 L/kg, and t1/2 of 2.64 hours.