Design and Optimization of Novel Benzimidazole- and Imidazo[4,5-]pyridine-Based ATM Kinase Inhibitors with Subnanomolar Activities.

The ATM kinase is a promising target in cancer treatment as an important regulator of the cellular response to DNA double-strand breaks. In this work, we present a new class of specific benzimidazole-based ATM inhibitors with picomolar potency against the isolated enzyme and favorable selectivity within relative PIKK and PI3K kinases. We could identify two promising inhibitor subgroups with significantly different physicochemical properties, which we developed simultaneously.