6t2w › Citations

The Discovery of 7-Methyl-2-[(7-methyl[1,2,4]triazolo[1,5-a]pyridin-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.

Goldberg FW, Finlay MRV, Ting AKT, Beattie D, Lamont GM, Fallan C, Wrigley GL, Schimpl M, Howard MR, Williamson B, Vazquez-Chantada M, Barratt DG, Davies BR, Cadogan EB, Ramos-Montoya A, Dean E
J Med Chem 63 3461-3471 (2020)
Related entries: 6t3b, 6t3c

Cited: 25 times
EuropePMC logo PMID: 31851518

Abstract

DNA-PK is a key component within the DNA damage response, as it is responsible for recognizing and repairing double-strand DNA breaks (DSBs) via non-homologous end joining. Historically it has been challenging to identify inhibitors of the DNA-PK catalytic subunit (DNA-PKcs) with good selectivity versus the structurally related PI3 (lipid) and PI3K-related protein kinases. We screened our corporate collection for DNA-PKcs inhibitors with good PI3 kinase selectivity, identifying compound

Articles - 6t2w mentioned but not cited (3)

  1. KUALA: a machine learning-driven framework for kinase inhibitors repositioning. De Simone G, Sardina DS, Gulotta MR, Perricone U. Sci Rep 12 17877 (2022)
  2. Discovery of pyrazolopyrimidines that selectively inhibit CSF-1R kinase by iterative design, synthesis and screening against glioblastoma cells. Baillache DJ, Valero T, Lorente-Macías Á, Bennett DJ, Elliott RJR, Carragher NO, Unciti-Broceta A. RSC Med Chem 14 2611-2624 (2023)
  3. Identification of Small-Molecule Inhibitors for Osteosarcoma Targeted Therapy: Synchronizing In Silico, In Vitro, and In Vivo Analyses. Liu J, Yao Q, Peng Y, Dong Z, Tang L, Su X, Liu L, Chen C, Ramalingam M, Cheng L. Front Bioeng Biotechnol 10 921107 (2022)


Reviews citing this publication (8)

  1. DNA damage repair: historical perspectives, mechanistic pathways and clinical translation for targeted cancer therapy. Huang R, Zhou PK. Signal Transduct Target Ther 6 254 (2021)
  2. Advances in synthetic lethality for cancer therapy: cellular mechanism and clinical translation. Topatana W, Juengpanich S, Li S, Cao J, Hu J, Lee J, Suliyanto K, Ma D, Zhang B, Chen M, Cai X. J Hematol Oncol 13 118 (2020)
  3. Targeting DNA Damage Response in Prostate and Breast Cancer. Wengner AM, Scholz A, Haendler B. Int J Mol Sci 21 E8273 (2020)
  4. Therapeutic Targeting of DNA Damage Response in Cancer. Choi W, Lee ES. Int J Mol Sci 23 1701 (2022)
  5. Development and Evolution of DNA-Dependent Protein Kinase Inhibitors toward Cancer Therapy. Matsumoto Y. Int J Mol Sci 23 4264 (2022)
  6. DNA Double Strand Break Repair Pathways in Response to Different Types of Ionizing Radiation. van de Kamp G, Heemskerk T, Kanaar R, Essers J. Front Genet 12 738230 (2021)
  7. DNA Repair and Therapeutic Strategies in Cancer Stem Cells. Gillespie MS, Ward CM, Davies CC. Cancers (Basel) 15 1897 (2023)
  8. Structure and Function of SNM1 Family Nucleases. Wu HY, Zheng Y, Laciak AR, Huang NN, Koszelak-Rosenblum M, Flint AJ, Carr G, Zhu G. Adv Exp Med Biol 1414 1-26 (2023)

Articles citing this publication (14)

  1. Radiotherapy is associated with a deletion signature that contributes to poor outcomes in patients with cancer. Kocakavuk E, Anderson KJ, Varn FS, Johnson KC, Amin SB, Sulman EP, Lolkema MP, Barthel FP, Verhaak RGW. Nat Genet 53 1088-1096 (2021)
  2. Inhibition of DNA-PK with AZD7648 Sensitizes Tumor Cells to Radiotherapy and Induces Type I IFN-Dependent Durable Tumor Control. Nakamura K, Karmokar A, Farrington PM, James NH, Ramos-Montoya A, Bickerton SJ, Hughes GD, Illidge TM, Cadogan EB, Davies BR, Dovedi SJ, Valge-Archer V. Clin Cancer Res 27 4353-4366 (2021)
  3. Structural insights into inhibitor regulation of the DNA repair protein DNA-PKcs. Liang S, Thomas SE, Chaplin AK, Hardwick SW, Chirgadze DY, Blundell TL. Nature 601 643-648 (2022)
  4. Structural analysis of the catalytic domain of Artemis endonuclease/SNM1C reveals distinct structural features. Karim MF, Liu S, Laciak AR, Volk L, Koszelak-Rosenblum M, Lieber MR, Wu M, Curtis R, Huang NN, Carr G, Zhu G. J Biol Chem 295 12368-12377 (2020)
  5. High-efficiency transgene integration by homology-directed repair in human primary cells using DNA-PKcs inhibition. Selvaraj S, Feist WN, Viel S, Vaidyanathan S, Dudek AM, Gastou M, Rockwood SJ, Ekman FK, Oseghale AR, Xu L, Pavel-Dinu M, Luna SE, Cromer MK, Sayana R, Gomez-Ospina N, Porteus MH. Nat Biotechnol (2023)
  6. A microfluidic system that replicates pharmacokinetic (PK) profiles in vitro improves prediction of in vivo efficacy in preclinical models. Singh D, Deosarkar SP, Cadogan E, Flemington V, Bray A, Zhang J, Reiserer RS, Schaffer DK, Gerken GB, Britt CM, Werner EM, Gibbons FD, Kostrzewski T, Chambers CE, Davies EJ, Montoya AR, Fok JHL, Hughes D, Fabre K, Wagoner MP, Wikswo JP, Scott CW. PLoS Biol 20 e3001624 (2022)
  7. Biochemical Targets and Molecular Mechanism of Ginsenoside Compound K in Treating Osteoporosis Based on Network Pharmacology. Zhang S, Shen S, Ma P, Fan D. Int J Mol Sci 23 13921 (2022)
  8. Effective Radiosensitization of Bladder Cancer Cells by Pharmacological Inhibition of DNA-PK and ATR. Chughtai AA, Pannhausen J, Dinger P, Wirtz J, Knüchel R, Gaisa NT, Eble MJ, Rose M. Biomedicines 10 1277 (2022)
  9. Mitochondrial E3 ligase MARCH5 is a safeguard against DNA-PKcs-mediated immune signaling in mitochondria-damaged cells. Heo J, Park YJ, Kim Y, Lee HS, Kim J, Kwon SH, Kang MG, Rhee HW, Sun W, Lee JH, Cho H. Cell Death Dis 14 788 (2023)
  10. Molecular docking studies of natural immunomodulators indicate their interactions with the CD40L of CD40/CD40L pathway and CSF1R kinase domain of microglia. Maurya SK, Mishra R. J Mol Model 28 101 (2022)
  11. Synthesis and Structural Optimization of 2,7,9-Trisubstituted purin-8-ones as FLT3-ITD Inhibitors. Tomanová M, Kozlanská K, Jorda R, Jedinák L, Havlíková T, Řezníčková E, Peřina M, Klener P, Dolníková A, Cankař P, Kryštof V. Int J Mol Sci 23 16169 (2022)
  12. AZD7648, a DNA-PKcs inhibitor, overcomes radioresistance in Hep3B xenografts and cells under tumor hypoxia. Ha J, Park M, Lee Y, Choi SH, Kim BS, Ha H, Jeong YK. Am J Cancer Res 13 4918-4930 (2023)
  13. Optimization of hERG and Pharmacokinetic Properties for Basic Dihydro-8H-purin-8-one Inhibitors of DNA-PK. Goldberg FW, Ting AKT, Beattie D, Lamont GM, Fallan C, Finlay MRV, Williamson B, Schimpl M, Harmer AR, Adeyemi OB, Nordell P, Cronin AS, Vazquez-Chantada M, Barratt D, Ramos-Montoya A, Cadogan EB, Davies BR. ACS Med Chem Lett 13 1295-1301 (2022)
  14. Regioselective Pd-catalyzed α-alkylation of furans using alkyl iodides. Yuan J, Zhang X, Yang C. RSC Adv 11 13832-13838 (2021)


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