AZD7648
DNA-PK inhibitor/CRISPR enhancer / AZD7648 is a very potent and selective (against 397 kinases) DNA-PK inhibitor (pIC50 = 9.2; cellular pIC50 = 7.0).1 It is a sensitizer of radiation- and doxorubicin-induced DNA damage and sustained tumor regression in xenograft and patient-derived xenograft models.2 AZD7648 significantly enhances precise CRISPR/Cas9 gene editing alone3,4,5 or in combined treatment with a DNA polymerase theta inhibitor (2iHDR cocktail)5.
Biochemicals & reagents
2230820-11-6
1) Goldberg et al. (2020), The Discovery of 7-Methyl-2-[(7-methyl[1,2,4]triazolo[1,5-a]pyridine-6-yl)amino]-9-(tetrahydro-2H-pyran-4-yl)-7,9-dihydro-8H-purin-8-one (AZD7648), a Potent and Selective DNA-Dependent Protein Kinase (DNA-PK) Inhibitor; J. Med. Chem. 63 3461 2) Fok et al. (2019), AZD7648 is a potent and selective DNA-PK inhibitor that enhances radiation, chemotherapy and Olaparib activity; Nat. Commun. 10 5065 3) Cloarec-Ung et al. (2024), Near-perfect precise on-target editing of human hematopoietic stem and progenitor cells; Elife 12 RP91288 4) Selvaraj et al. (2024), High-efficiency transgene integration by homology-directed repair in human primary cells using DNA-PKcs inhibition; Nat. Biotech. 42 731 5) Wimberger et al. (2023), Simultaneous inhibition of DNA-PK and Pol? improves integration efficiency and precision of genome editing; Nat. Commun. 14 4761
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TARGET: Kinase; DNA -- PATHWAY: DNA damage -- RESEARCH AREA: CRISPR -- DISEASE AREA: Cancer