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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
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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Abbreviations
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
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
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.
Clinical trial information
Select trial for more information
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Abbreviations
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