MedKoo Biosciences, Inc.
Tel:   +1-919-636-5577    Fax:   +1-919-980-4831    Email:   sales@medkoo.com
Search
Login Register
Search
MedKoo Cat#: 408010 | Name: AZD-7648
Featured New

Description:

WARNING: This product is for research use only, not for human or veterinary use.

AZD-7648 is a potent and selective DNA-PK inhibitor.

Chemical Structure

AZD-7648
AZD-7648
CAS#2230820-11-6

Theoretical Analysis

MedKoo Cat#: 408010

Name: AZD-7648

CAS#: 2230820-11-6

Chemical Formula: C18H20N8O2

Exact Mass: 380.1709

Molecular Weight: 380.41

Elemental Analysis: C, 56.83; H, 5.30; N, 29.46; O, 8.41

Price and Availability

Size Price Availability Quantity
10mg USD 150.00 Ready to ship
25mg USD 250.00 Ready to ship
50mg USD 400.00 Ready to ship
100mg USD 700.00 Ready to ship
200mg USD 1,150.00 Ready to ship
500mg USD 2,550.00 Ready to ship
1g USD 3,650.00 Ready to ship
2g USD 6,450.00 Ready to ship
Show More
Bulk Inquiry
Buy Now
Add to Cart
Related CAS #
No Data
Synonym
AZD-7648; AZD 7648; AZD7648;
IUPAC/Chemical Name
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
InChi Key
XISVSTPEXYIKJL-UHFFFAOYSA-N
InChi Code
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)
SMILES Code
CC1=CC2=NC=NN2C=C1NC3=NC=C(N(C)C(N4C5CCOCC5)=O)C4=N3
Appearance
Solid powder
Purity
>98% (or refer to the Certificate of Analysis)
Shipping Condition
Shipped under ambient temperature as non-hazardous chemical. This product is stable enough for a few weeks during ordinary shipping and time spent in Customs.
Storage Condition
Dry, dark and at 0 - 4 C for short term (days to weeks) or -20 C for long term (months to years).
Solubility
Soluble in DMSO
Shelf Life
>3 years if stored properly
Drug Formulation
This drug may be formulated in DMSO
Stock Solution Storage
0 - 4 C for short term (days to weeks), or -20 C for long term (months).
HS Tariff Code
2934.99.9001
More Info
Biological target:
AZD-7648 is a DNA-PK inhibitor with an IC50 of 0.6 nM.
In vitro activity:
To evaluate the radio-sensitizing characteristics of AZD7648, the kinetics of DNA damage following AZD7648 treatment in (ionizing radiation) IR-treated A549 non-small-cell lung cancer (NSCLC) cells were evaluated. IR treatment of vehicle-treated control cells led to γH2AX, 53BP1 and pATM foci formation, which recovered to baseline by 6 h (Fig. 1c). Similar results were observed in conditions whereby cells received 1 h pre-treatment of AZD7648 at concentrations below the IC50 (<91 nM). However, at concentrations greater than the AZD7648 IC50, γH2AX, 53BP1 and pATM foci persisted at least until 72 h after IR treatment, suggesting that DNA repair was delayed by DNA-PK inhibition with AZD7648. These data correlate with the appearance of micronuclei and a prolonged G2/M cell cycle arrest at later time points, further confirming persistence of DNA damage when combining IR with AZD7648 (Fig. 1c, d). The combination of AZD7648 with IR led to a concentration-dependent decrease in clonogenic survival of A549 and NCI-H1299 NSCLC cells (Fig. 1e, Supplementary Table 2). Together these data demonstrate in vitro that AZD7648 leads to the persistence of DNA damage following IR, resulting in G2/M DNA damage checkpoint activation, genome instability and reduced cellular survival. Reference: Nat Commun. 2019 Nov 7;10(1):5065. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6838110/
In vivo activity:
AZD7648 administered orally at a tolerated dose of 100 mg kg−1 once daily (qd) enhanced the response to fractionated IR (2 Gy for five consecutive days) in mice implanted with A549 xenografts (Fig. 2a). While tumours were insensitive to single-agent AZD7648 treatment, IR treatment alone induced tumour growth inhibition (TGI) by 50%, but the combination of AZD7648 with IR (AZD7648 followed by IR 1 h later in the first 5 days of the study) achieved 90% TGI. This in vivo radio-sensitization was shown to be dose-dependent in NCI-H1299 xenografts, where the combination (AZD7648 100 or 50 mg kg−1 qd × 21 days + IR 2 Gy qd × 5 days) achieved 85% or 55% tumour regression compared with 60% TGI induced by IR alone (Fig. 2b). Reference: Nat Commun. 2019 Nov 7;10(1):5065. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6838110/
Solvent mg/mL mM
Solubility
DMSO 5.5 14.46
Note: There can be variations in solubility for the same chemical from different vendors or different batches from the same vendor. The following factors can affect the solubility of the same chemical: solvent used for crystallization, residual solvent content, polymorphism, salt versus free form, degree of hydration, solvent temperature. Please use the solubility data as a reference only. Warming and sonication will facilitate dissolving. Still have questions? Please contact our Technical Support scientists.

Preparing Stock Solutions

The following data is based on the product molecular weight 380.41 Batch specific molecular weights may vary from batch to batch due to the degree of hydration, which will affect the solvent volumes required to prepare stock solutions.

Recalculate based on batch purity %
Concentration / Solvent Volume / Mass 1 mg 5 mg 10 mg
1 mM 1.15 mL 5.76 mL 11.51 mL
5 mM 0.23 mL 1.15 mL 2.3 mL
10 mM 0.12 mL 0.58 mL 1.15 mL
50 mM 0.02 mL 0.12 mL 0.23 mL
Formulation protocol:
1. Fok JHL, Ramos-Montoya A, Vazquez-Chantada M, Wijnhoven PWG, Follia V, James N, Farrington PM, Karmokar A, Willis SE, Cairns J, Nikkilä J, Beattie D, Lamont GM, Finlay MRV, Wilson J, Smith A, O'Connor LO, Ling S, Fawell SE, O'Connor MJ, Hollingsworth SJ, Dean E, Goldberg FW, Davies BR, Cadogan EB. AZD7648 is a potent and selective DNA-PK inhibitor that enhances radiation, chemotherapy and olaparib activity. Nat Commun. 2019 Nov 7;10(1):5065. doi: 10.1038/s41467-019-12836-9. PMID: 31699977; PMCID: PMC6838110. 2. 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. Inhibition of DNA-PK with AZD7648 Sensitizes Tumor Cells to Radiotherapy and Induces Type I IFN-Dependent Durable Tumor Control. Clin Cancer Res. 2021 May 19. doi: 10.1158/1078-0432.CCR-20-3701. Epub ahead of print. PMID: 34011558.
In vitro protocol:
1. Fok JHL, Ramos-Montoya A, Vazquez-Chantada M, Wijnhoven PWG, Follia V, James N, Farrington PM, Karmokar A, Willis SE, Cairns J, Nikkilä J, Beattie D, Lamont GM, Finlay MRV, Wilson J, Smith A, O'Connor LO, Ling S, Fawell SE, O'Connor MJ, Hollingsworth SJ, Dean E, Goldberg FW, Davies BR, Cadogan EB. AZD7648 is a potent and selective DNA-PK inhibitor that enhances radiation, chemotherapy and olaparib activity. Nat Commun. 2019 Nov 7;10(1):5065. doi: 10.1038/s41467-019-12836-9. PMID: 31699977; PMCID: PMC6838110. 2. 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. Inhibition of DNA-PK with AZD7648 Sensitizes Tumor Cells to Radiotherapy and Induces Type I IFN-Dependent Durable Tumor Control. Clin Cancer Res. 2021 May 19. doi: 10.1158/1078-0432.CCR-20-3701. Epub ahead of print. PMID: 34011558.
In vivo protocol:
1. Fok JHL, Ramos-Montoya A, Vazquez-Chantada M, Wijnhoven PWG, Follia V, James N, Farrington PM, Karmokar A, Willis SE, Cairns J, Nikkilä J, Beattie D, Lamont GM, Finlay MRV, Wilson J, Smith A, O'Connor LO, Ling S, Fawell SE, O'Connor MJ, Hollingsworth SJ, Dean E, Goldberg FW, Davies BR, Cadogan EB. AZD7648 is a potent and selective DNA-PK inhibitor that enhances radiation, chemotherapy and olaparib activity. Nat Commun. 2019 Nov 7;10(1):5065. doi: 10.1038/s41467-019-12836-9. PMID: 31699977; PMCID: PMC6838110. 2. 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. Inhibition of DNA-PK with AZD7648 Sensitizes Tumor Cells to Radiotherapy and Induces Type I IFN-Dependent Durable Tumor Control. Clin Cancer Res. 2021 May 19. doi: 10.1158/1078-0432.CCR-20-3701. Epub ahead of print. PMID: 34011558.
1: Lapa BS, Costa MI, Figueiredo D, Jorge J, Alves R, Monteiro AR, Serambeque B, Laranjo M, Botelho MF, Carreira IM, Sarmento-Ribeiro AB, Gonçalves AC. AZD-7648, a DNA-PK Inhibitor, Induces DNA Damage, Apoptosis, and Cell Cycle Arrest in Chronic and Acute Myeloid Leukemia Cells. Int J Mol Sci. 2023 Oct 18;24(20):15331. doi: 10.3390/ijms242015331. PMID: 37895013; PMCID: PMC10607085. 2: 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. High-efficiency transgene integration by homology- directed repair in human primary cells using DNA-PKcs inhibition. Nat Biotechnol. 2024 May;42(5):731-744. doi: 10.1038/s41587-023-01888-4. Epub 2023 Aug 3. PMID: 37537500. 3: Fok JHL, Ramos-Montoya A, Vazquez-Chantada M, Wijnhoven PWG, Follia V, James N, Farrington PM, Karmokar A, Willis SE, Cairns J, Nikkilä J, Beattie D, Lamont GM, Finlay MRV, Wilson J, Smith A, O'Connor LO, Ling S, Fawell SE, O'Connor MJ, Hollingsworth SJ, Dean E, Goldberg FW, Davies BR, Cadogan EB. AZD7648 is a potent and selective DNA-PK inhibitor that enhances radiation, chemotherapy and olaparib activity. Nat Commun. 2019 Nov 7;10(1):5065. doi: 10.1038/s41467-019-12836-9. PMID: 31699977; PMCID: PMC6838110. 4: Zhang W, Li W, Yin C, Feng C, Liu B, Xu H, Jin X, Tu C, Li Z. PRKDC Induces Chemoresistance in Osteosarcoma by Recruiting GDE2 to Stabilize GNAS and Activate AKT. Cancer Res. 2024 Sep 4;84(17):2873-2887. doi: 10.1158/0008-5472.CAN-24-0163. PMID: 38900943; PMCID: PMC11372366. 5: Wimberger S, Akrap N, Firth M, Brengdahl J, Engberg S, Schwinn MK, Slater MR, Lundin A, Hsieh PP, Li S, Cerboni S, Sumner J, Bestas B, Schiffthaler B, Magnusson B, Di Castro S, Iyer P, Bohlooly-Y M, Machleidt T, Rees S, Engkvist O, Norris T, Cadogan EB, Forment JV, Šviković S, Akcakaya P, Taheri-Ghahfarokhi A, Maresca M. Simultaneous inhibition of DNA-PK and Polϴ improves integration efficiency and precision of genome editing. Nat Commun. 2023 Aug 14;14(1):4761. doi: 10.1038/s41467-023-40344-4. PMID: 37580318; PMCID: PMC10425386. 6: Cullot G, Aird EJ, Schlapansky MF, Yeh CD, van de Venn L, Vykhlyantseva I, Kreutzer S, Mailänder D, Lewków B, Klermund J, Montellese C, Biserni M, Aeschimann F, Vonarburg C, Gehart H, Cathomen T, Corn JE. Genome editing with the HDR-enhancing DNA-PKcs inhibitor AZD7648 causes large-scale genomic alterations. Nat Biotechnol. 2024 Nov 27. doi: 10.1038/s41587-024-02488-6. Epub ahead of print. PMID: 39604565. 7: Cloarec-Ung FM, Beaulieu J, Suthananthan A, Lehnertz B, Sauvageau G, Sheppard HM, Knapp DJHF. Near-perfect precise on-target editing of human hematopoietic stem and progenitor cells. Elife. 2024 Jun 3;12:RP91288. doi: 10.7554/eLife.91288. PMID: 38829685; PMCID: PMC11147503. 8: Kim HR, Park SJ, Cho YS, Moyo MK, Choi JU, Lee NK, Chung SW, Kweon S, Park J, Kim B, Ko YG, Yeo JH, Lee J, Kim SY, Byun Y. Stimulating macropinocytosis of peptide-drug conjugates through DNA-dependent protein kinase inhibition for treating KRAS-mutant cancer. J Control Release. 2024 Aug;372:176-193. doi: 10.1016/j.jconrel.2024.06.028. Epub 2024 Jun 20. PMID: 38880331. 9: Liang S, Thomas SE, Chaplin AK, Hardwick SW, Chirgadze DY, Blundell TL. Structural insights into inhibitor regulation of the DNA repair protein DNA- PKcs. Nature. 2022 Jan;601(7894):643-648. doi: 10.1038/s41586-021-04274-9. Epub 2022 Jan 5. PMID: 34987222; PMCID: PMC8791830. 10: Fabbrizi MR, Doggett TJ, Hughes JR, Melia E, Dufficy ER, Hill RM, Goula A, Phoenix B, Parsons JL. Inhibition of key DNA double strand break repair protein kinases enhances radiosensitivity of head and neck cancer cells to X-ray and proton irradiation. Cell Death Discov. 2024 Jun 12;10(1):282. doi: 10.1038/s41420-024-02059-3. PMID: 38866739; PMCID: PMC11169544.