AZD7648   Click here for help

GtoPdb Ligand ID: 10601

Synonyms: AZD-7648 | compound 16 [PMID: 31851518]
PDB Ligand
Compound class: Synthetic organic
Comment: AZD7648 is a selective inhibitor of DNA-dependent protein kinase (DNA-PK) [1]. DNA-PK is responsible for recognising and repairing double-strand DNA breaks in damaged DNA, and is a cancer drug target. AZD7648 is orally bioavailable.
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2D Structure
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Physico-chemical Properties
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Hydrogen bond acceptors 6
Hydrogen bond donors 1
Rotatable bonds 3
Topological polar surface area 104.16
Molecular weight 380.17
XLogP 0.4
No. Lipinski's rules broken 0
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Canonical SMILES Cc1cc2ncnn2cc1Nc1ncc2c(n1)n(C1CCOCC1)c(=O)n2C
Isomeric SMILES Cc1cc2ncnn2cc1Nc1ncc2c(n1)n(C1CCOCC1)c(=O)n2C
InChI InChI=1S/C18H20N8O2/c1-11-7-15-20-10-21-25(15)9-13(11)22-17-19-8-14-16(23-17)26(18(27)24(14)2)12-3-5-28-6-4-12/h7-10,12H,3-6H2,1-2H3,(H,19,22,23)
Bioactivity Comments
AZD7648 is minimally active vs. the potential off-target lipid kinases PI3Kα and PI3Kγ, and does not inhibit any other protein kinases [1]. The anti-tumour activity of AZD7648 is enhanced in xenograft models when given in combination with other anti-cancer drugs that increase double-strand DNA breaks (e.g. the anthracycline doxorubicin or the PARP inhibitor olaparib).
Selectivity at enzymes
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Target Sp. Type Action Value Parameter Concentration range (M) Reference
protein kinase, DNA-activated, catalytic subunit Primary target of this compound Hs Inhibitor Inhibition 7.0 – 9.2 pIC50 - 1
pIC50 9.2 (IC50 6.3x10-10 M) [1]
Description: Measured by time-resolved fluorescence (TR-FRET) in a biochemical assay.
pIC50 7.0 (IC50 9.1x10-8 M) [1]
Description: Measuring inhibition of irradiation-induced DNA-PK autophosphorylation in A549 cells by ELISA.
phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit gamma Hs Inhibitor Inhibition 7.3 pIC50 - 1
pIC50 7.3 (IC50 5.2x10-8 M) [1]
phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha Hs Inhibitor Inhibition 7.0 pIC50 - 1
pIC50 7.0 (IC50 1x10-7 M) [1]