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ATM kinase inhibition

CompoundAZD1390

Area under investigation

Primary glioblastoma multiforme and recurrent glioblastoma multiforme

Scientific PillarDNA Damage Response

 

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NCT03423628 trial overview

Tumor

Primary glioblastoma multiforme and recurrent glioblastoma multiforme

Trial Identifier

NCT03423628

Phase

I

Regimen

AZD1390 + radiotherapy

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NCT03423628 trial overview

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Target Overview

ATM together with ATR and DNA-PK is 1 of 3 key serine/threonine PI3-kinase-like-protein-kinases involved in the DNA damage response.1

ATM specifically coordinates the signaling and repair of chromosomal DNA double-strand breaks. Accordingly, inhibition of ATM makes tumors hypersensitive to agents that lead to DSBs, such as chemotherapies, radiation therapy, and other inhibitors of the DNA damage response.2,3

Compound Overview

AZD1390 is a potent and selective orally bioavailable ATM inhibitor that was specifically optimized for use in central nervous system malignancies. It is being investigated as a potential cancer treatment in advanced tumors.

Mechanism of Action

  • Mechanism of Action

References

1. Durant ST, et al. Sci Adv. 2018;4(6):eaat1719. 2. Shiloh Y, Ziv Y. Nat Rev Mol Cell Biol. 2013;14(4):197-210. 3. Blackford AN, Jackson SP. Mol Cell. 2017;66(6):801-817.

 

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NCT03423628 trial overview

Tumor

Primary glioblastoma multiforme and recurrent glioblastoma multiforme

Trial Identifier

NCT03423628

Phase

I

Regimen

AZD1390 + radiotherapy

Visit ct.gov

NCT03423628 Overview Modal

NCT03423628 trial overview

Take me to ClinicalTrials.Gov

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Abbreviations

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  • 53BP1

    p53 binding protein 1

  • ATM

    ataxia telangiectasia mutated

  • ATR

    ataxia telangiectasia and Rad3-related

  • CHEK

    checkpoint kinase

  • CHK2

    serine/threonine-protein kinase Chk2

  • CNS

    central nervous system

  • DNA-PK

    DNA-dependent protein kinase

  • DSB

    double-strand break

  • H2AX

    H2A histone family member X

  • KAP1

    Krüppel-associated box domain-associated protein 1

  • M phase

    mitotic phase

  • MDC1

    mediator of DNA damage checkpoint protein 1

  • MRN

    MRE11-RAD50-NBS1

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Veeva ID: Z4-84958 US-109129 DE-92568 Last Updated October 20263/26
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