molecules of the month

14. The Novartis pan-serotype dengue virus (DENV) NS4B protein inhibitor, NITD-688, is a preclinical candidate with strong activity against all four serotypes of DENV in vitro and excellent oral efficacy in a mouse model. The starting point was identified through phenotypic screening of 1.5M compounds and counterselection against host factors and cytotoxicity. The target was identified through resistance mutations and binding confirmed by 15N-NMR. Allometric scaling was used to predict a human efficacious dose of 35 mg QD. Non-GLP studies showed good tolerability in dog up to 80 mg/kg, and QTc prolongation was not observed despite partial inhibition of hERG in vitro. The authors allude to designing a trial to ensure patients are recruited within 48 h of fever onset…