CVN293 is a selective and brain-permeable potassium ion (K+) channel KCNK13 inhibitor with IC50 values of 41 nM for hKCNK13 and 28 nM for mKCNK13, respectively. CVN293 potently inhibits the NLRP3-inflammasome-mediated production of the pro-inflammatory cytokine IL-1β in microglia [1].

hKCNK13:41 nM, mKCNK13:28 nM, hKCNK6:>30000 nM

CVN293 (0.05, 0.5, 5 μM) exhibits a dose-dependent inhibitory effect on LPS-induced IL-1β production in mouse microglial cells mediated by the NLRP3 inflammasome [1].

Pharmacokinetic Parameters of CVN293 were evaluated in male Sprague-Dawley rats, dogs, and cynomolgus monkeys [1]. In rats, IV (0.5 mg/kg) and PO (3 mg/kg) administration resulted in T_max of 1.0 h, C_max of 468 ng/mL, AUC_0-∞ of 222 ng•h/mL, 1236 ng•h/mL, t_1/2 of 1.0 h and 2.0 h, CLp of 35 mL/min/kg, and V_ss of 1.85 L/kg with F at 87%. In dogs, IV (1 mg/kg) and PO (10 mg/kg) administration yielded a T_max of 1.0 h, C_max of 241 ng/mL, AUC_0-∞ of 438 ng•h/mL, 630 ng•h/mL, t_1/2 of 0.5 h and 2.6 h, CLp of 38 mL/min/kg, and V_ss of 1.42 L/kg with F at 41%. For cynomolgus monkeys, IV (1 mg/kg) and PO (3 mg/kg) resulted in T_max of 1.0 h, C_max of 165 ng/mL, AUC_0-∞ of 782 ng•h/mL, 546 ng•h/mL, t_1/2 of 1.1 h and 1.9 h, CLp of 22 mL/min/kg, and V_ss of 1.45 L/kg with F at 24%.