TC-6683

TC-6683 (AZD1446) is a potent and highly selective α4β2 nAChR agonist with Ki of 30/34 nM against hα4β2/rα4β2, with little to no affinity against h α3β2 and h α7 (Ki>6.7 uM).TC-6683 (10 uM) produced <30% inhibition of specific binding or enzyme activity at all targets except the human (87%) and murine (97%) 5-HT3 receptors at a panel of 70 receptors, ion channels, and enzymes at NovaScreen/Caliper.TC-6683 (AZD1446) enhanced working memory in the object recognition paradigm in rats at every dose tested (0.1−3 mg/kg, po), exhibited favorable pharmaceutical properties and in vivo efficacy in animal models.

1. Mazurov AA, et al. J Med Chem. 2012 Nov 8;55(21):9181-94. 2. Jucaite A, et al. Psychopharmacology (Berl). 2014 Mar;231(6):1251-65. 3. Canning BJ, et al. J Pharmacol Exp Ther. 2022 Feb;380(2):94-103.