Small molecule ATM inhibitors as potential cancer therapy: a patent review (2003-present).

Abstract

Introduction: The ataxia telangiectasia mutated kinase (ATM) is key in coordinating the DDR signaling network essential for responding to double-strand breaks (DSBs). Several ATM inhibitors are being investigated for potential anticancer treatment in clinical trials.

Areas covered: This review aims to provide a comprehensive overview of patents and patent applications since 2003, with a particular focus on the structural properties, activity and efficacy of the claimed ATM kinase small-molecule inhibitors. The search was conducted using SciFinder, Cortellis Drug Discovery Intelligence Database, and Espacenet. After filtering, 44 records were identified for further analysis. This paper also discusses the recent progress in the clinical trials and development history.

Expert opinion: ATM kinase is a promising target for cancer therapy. Small-molecule ATM kinase inhibitors hold significant potential in cancer treatment by enhancing the efficacy of existing DNA-damaging therapies. Patent analysis revealed that the majority of these compounds contain imidazo[4,5-c]quinolinone scaffold or its bioisosteric variations which are optimal in terms of good ATM inhibitory activity and selectivity over closely related enzymes. Clinical trials explore combinations with RT or DNA-targeted compounds like PARP inhibitors, which induce DSBs. The medicinal chemistry field anticipates that these therapeutic options will soon be available on the pharmaceutical market.