NKCC Activator

CAII-IN-12 (compound 6c) is a potent and selective carbonic anhydrase (CA) II and VII inhibitor (hCA II K_i = 47.8 nM, hCA VII K_i = 3.6 nM) with anti-epilepitic activity. CAII-IN-12 displays selectivity over hCA I (K_i = 370 nM). CAII-IN-12 exhibits potent anticonvulsant activity in both Pentylenetetrazol- and Pilocarpine (HY-B0726A)-induced seizure mouse models. CAII-IN-12 increases expression of KCC2 in the hippocampus, maintains neuronal integrity, and reduces mTOR activity. CAII-IN-12 can be used for epilepsy research.

CAII/VII-IN-1 is an orally active hCA II (K_I = 12.3 nM), and hCA VII (K_I = 22.6 nM) inhibitor, showing no significant activity against hCA I. CAII/VII-IN-1 shows excellent neuroprotective activity in vivo Pilocarpine (HY-B0726A)-induced seizure model. CAII/VII-IN-1 can upregulate KCC2 and inhibit mTOR, exerting neuroprotective effects. CAII/VII-IN-1 does not show any significant neurotoxic effects or alterations in liver and kidney function. CAII/VII-IN-1 can be used for the study of epilepsy.