clemizole analogue 20

Clemizole analogue 20 (also known as Compound 20) is a small molecule indazole-based derivative of the antihistamine clemizole. It was originally developed as an antiviral agent targeting the Hepatitis C virus (HCV) NS4B protein, where it demonstrated activity against genotype 1b replicons (EC50 = 3.3 μM). However, its development for HCV was hindered by potential cardiac safety concerns due to hERG inhibition (IC50 = 2.8 μM). Subsequent research in phenotypic zebrafish models of Dravet syndrome identified Compound 20 as a potent anti-seizure agent. Its antiepileptic activity is primarily mediated through its binding and activation of the serotonin 5-HT2B receptor (Ki = 772 nM), with high selectivity over 5-HT2A and 5-HT2C subtypes. Structurally, it features an indazole core that replaces the benzimidazole moiety of clemizole.