AZD7648

DNA-PK inhibitor that enhances radiation, chemotherapy, and olaparib activity

Also Known As:

7-methyl-2-((7-methyl(1,2,4)triazolo(1,5- a)pyridin-6-yl)amino)-9-(tetrahydro-2 H-pyran-4-yl)-7,9-dihydro-8 H-purin-8-one; 7-methyl-2-((7-methyl-(1,2,4)triazolo(1,5-a)pyridin-6-yl)amino)-9-(oxan-4-yl)purin-8-one; AZD-7648

Networked: 12 relevant articles (0 outcomes, 6 trials/studies)

Bio-Agent Context: Research Results

Heterocyclic Compounds: 198
- 1-Ring Heterocyclic Compounds
  - Azoles: 2138
    - Triazoles: 1533
      - AZD7648: 12
  - Pyrans: 130
    - AZD7648: 12
- Fused-Ring Heterocyclic Compounds
  - 2-Ring Heterocyclic Compounds
    - Purines: 651
      - AZD7648: 12

Experts

1.	Cadogan, Elaine B: 3 articles (01/2022 - 11/2019)
2.	Ramos-Montoya, Antonio: 3 articles (01/2022 - 11/2019)
3.	James, Neil: 2 articles (01/2022 - 11/2019)
4.	Wilson, Joanne: 2 articles (01/2022 - 11/2019)
5.	Davies, Barry R: 2 articles (01/2021 - 11/2019)
6.	Farrington, Paul M: 2 articles (01/2021 - 11/2019)
7.	Karmokar, Ankur: 2 articles (01/2021 - 11/2019)
8.	Chen, Jianjun: 1 article (07/2022)
9.	Cheng, Binbin: 1 article (07/2022)
10.	Ding, Zongbao: 1 article (07/2022)

Related Diseases

1.	Neoplasms (Cancer) 01/01/2023 - "The present data suggest that AZD7648 may be a strong radiosensitizer in radioresistant as well as radiosensitive cancers." 01/01/2023 - "The results showed that AZD7648 enhanced ionizing radiation (IR)-induced tumor growth not only in radiosensitive but also radioresistant tumors. " 01/01/2021 - "Blocking the NHEJ DNA repair pathway with AZD7648 in combination with RT leads to durable immune-mediated tumor control." 01/01/2021 - "AZD7648, when delivered in combination with RT, induced complete tumor regressions in a significant proportion of mice. " 11/20/2023 - "In vivo studies were performed with patient-derived xenograft models to evaluate the effects of AZD7648 in combination with chemotherapy or ionizing radiation on tumor growth. "
2.	Ovarian Neoplasms (Ovarian Cancer) 10/16/2023 - "AZD7648 is a potent DNA-PK inhibitor that is being developed for the treatment of ovarian cancer. " 01/01/2022 - "This work suggests that AZD7648, an inhibitor of DNA-PK, dosed in combination with PLD or olaparib is an exciting therapeutic option that could benefit patients with ovarian cancer and should be explored in clinical trials." 01/01/2022 - "The DNA-PK Inhibitor AZD7648 Sensitizes Patient-Derived Ovarian Cancer Xenografts to Pegylated Liposomal Doxorubicin and Olaparib Preventing Abdominal Metastases."
3.	Hypoxia (Hypoxemia) 01/01/2023 - "In vitro studies, AZD7648 plus IR increased IR-induced G2/M arrest and regulated cell cycle checkpoints such as cyclinB1, p-cdc2 in normoxia but not in hypoxia. " 01/01/2023 - "AZD7648 induced more radiation-mediated ROS than radiation only under normoxia, but these ROS were not altered by AZD7648 under hypoxia. " 01/01/2022 - "AZD7648 potently radiosensitised both cell lines, with similar sensitiser enhancement ratios for 10% survival (SER10) under oxia and anoxia. " 01/01/2023 - "In particular, the combination of AZD7648 with radiation reduced the expression of hypoxia induce factor-1α (HIF-1α) in radioresistant tumors. " 01/01/2022 - "Radiosensitisation of human (UT-SCC-54C) and murine (SCCVII) HNSCC cells by AZD7648 under oxia and anoxia was evaluated by clonogenic assay. "
4.	Genomic Instability 11/07/2019 - "Using ATM-deficient cells, we demonstrate that AZD7648, in combination with the PARP inhibitor olaparib, increases genomic instability, resulting in cell growth inhibition and apoptosis. "
5.	Disease Progression 01/01/2022 - "We investigated the efficacy to delay disease progression by the DNA-dependent protein kinase (DNA-PK) inhibitor AZD7648, administered in combination with two of the therapeutic options for patient management: either pegylated liposomal doxorubicin (PLD) or the PARP inhibitor olaparib. "

Related Drugs and Biologics

1.	DNA (Deoxyribonucleic Acid)
2.	olaparib
3.	8- dibenzothiophen- 4- yl- 2- morpholin- 4- yl- chromen- 4- one
4.	lysyl- arginyl- alanyl- lysyl- alanyl- lysyl- threonyl- threonyl- lysyl- lysyl- arginine (PKCS)
5.	1-dodecylpyridoxal (PLD)
6.	peposertib
7.	Poly(ADP-ribose) Polymerase Inhibitors
8.	DNA-Activated Protein Kinase
9.	A-Form DNA (A-DNA)
10.	liposomal doxorubicin (Doxil)

Related Therapies and Procedures

1.	Therapeutics
2.	Drug Therapy (Chemotherapy)
3.	Radiotherapy