CVN417

Potency assay (off target): Selective against subunit Alpha3 and Alpha4. IC50 2560 nM and 657 nM respectively. Outside Target Family: CVN417 was tested in a broad panel of 109 pharmacological receptors that included representatives of all prominent target classes such as membrane proteins (ion channels, GPCRs, transporters), kinases, and enzymes. The following receptors gave a response greater than 50% (performed at 10 μM) in these binding assays: the human dopamine D4.2 receptor (90%, antagonist binding), the rat imidazoline I2 receptor (84% antagonist binding), the human norepinephrine uptake transporter (NET, 62%), and the guinea pig sigma (51%, agonist binding). Noteworthy, with only 13% inhibition observed at 10 μM, CVN417 showed excellent selectivity over the nAChRα7 isoform. The activities at the I2 and the sigma receptors at 10 μM were considered unlikely to interfere with α6*-nAChR pharmacology and were not pursued in more detail, but full concentration response studies were performed for the NET (IC50 = 44.7 μM) and the D4.2 receptor (IC50 = 1.29 μM).