The Development of Ataxia Telangiectasia Mutated Kinase Inhibitors

Title:The Development of Ataxia Telangiectasia Mutated Kinase Inhibitors

Volume: 14 Issue: 10

Author(s): Martin Andrs, Jan Korabecny, Eugenie Nepovimova, Daniel Jun, Zdenek Hodny, Simona Moravcova, Hana Hanzlikova and Kamil Kuca

Affiliation:

Keywords: Ataxia telangiectasia mutated, cancer, chemosensitization, DNA damage response, phosphatidylinositol 3-kinaserelated protein kinases, radiosensitization.

Abstract: Radiation and genotoxic drugs are two of the cornerstones of current cancer treatment strategy. However, this type of therapy often suffers from radio- or chemo-resistance caused by DNA repair mechanisms. With the aim of increasing the efficacy of these treatments, there has been great interest in studying DNA damage responses (DDR). Among the plethora of signal and effector proteins involved in DDR, three related kinases ATM (ataxia telangiectasia mutated), ATR (ATM and Rad3-related) and DNA-PK (DNA-dependent protein kinase) play the main roles in initiation and regulation of signaling pathways in response to DNA double and single strand breaks (DSB and SSB). ATM inhibitors, as well as those of ATR and DNA-PK, provide an opportunity to sensitize cancer cells to therapy. Moreover, they can lead to selective killing of cancer cells, exploiting a concept known as synthetic lethality. However, only a very few selective inhibitors have been identified to this date. This mini-review is focused both on the development of selective inhibitors of ATM and other inhibitors which have ATM as one of their targets.

Cite this article as:

Andrs Martin, Korabecny Jan, Nepovimova Eugenie, Jun Daniel, Hodny Zdenek, Moravcova Simona, Hanzlikova Hana and Kuca Kamil, The Development of Ataxia Telangiectasia Mutated Kinase Inhibitors, Mini-Reviews in Medicinal Chemistry 2014; 14 (10) . https://dx.doi.org/10.2174/1389557514666140820123656