Discovery of NVP‐LEQ506, a Second‐Generation Inhibitor of Smoothened. Issue 8 (2nd July 2013) - Peukert, Stefan
Abstract First disclosure: Continued optimization provided a novel type of Smoothened (Smo) antagonist based on a pyridazine core. The compound, NVP‐LEQ506, currently in phase I clinical trials, combines high intrinsic potency and good pharmacokinetic properties resulting in excellent efficacy in rodent tumor models of medulloblastoma. Activity against a Smo mutant conferring resistance observed in a previous clinical trial with a competitor compound suggests additional therapeutic potential.