CVN293 is a selective inhibitor of the potassium channel KCNK13, with the advantages of brain permeability and oral bioavailability. It inhibits the production of the pro-inflammatory cytokine IL-1β induced by NLRP3 in microglia and can be used for research into neurodegenerative diseases.

KCNK13 (human):41 nM, KCNK13 (mouse):28 nM, KCNK6 (human):>30000 nM

Method:
CVN293 was administered intravenously and orally to male Sprague-Dawley rats, dogs, and cynomolgus monkeys. Blood samples were collected to measure plasma drug concentrations and calculate key pharmacokinetic parameters.

Result:
CVN293 exhibited distinct pharmacokinetic profiles in rats, dogs, and cynomolgus monkeys, with oral bioavailability of 87%, 41%, and 24%, respectively. The half-life ranged from 0.5 to 2.6 hours, and clearance and volume of distribution varied among species, reflecting interspecies metabolic differences. [1]

Method:
Mouse microglial cells were treated with different concentrations of CVN293 (0.05, 0.5, and 5 μM), followed by lipopolysaccharide (LPS) stimulation to induce inflammation and activate the NLRP3 inflammasome.

Result:
CVN293 exhibited a concentration-dependent inhibitory effect on IL-1β secretion mediated by the NLRP3 inflammasome in mouse microglial cells at concentrations of 0.05, 0.5, and 5 μM. [1]