The Development of Ataxia Telangiectasia Mutated Kinase Inhibitors

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

Journal Name: Mini-Reviews in Medicinal Chemistry

Volume 14 , Issue 10 , 2014

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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.

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

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Article Details

VOLUME: 14
ISSUE: 10
Year: 2014
Page: [805 - 811]
Pages: 7
DOI: 10.2174/1389557514666140820123656
Price: $65

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