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| 5mg |
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Purity: ≥98%
AZD-7648 (AZD7648) is a novel, potent and selective DNA-PK (DNA-dependent protein kinase) inhibitor with potential anticancer/antitumor activity. In xenograft and patient-derived xenograft (PDX) models, AZD7648 induces sustained regressions as an effective sensitizer of radiation- and doxorubicin-induced DNA damage. The PRKDC or XRCC7 gene in humans is responsible for encoding the enzyme DNA-dependent protein kinase, catalytic subunit, also known as DNA-PKcs. Phosphatidylinositol 3-kinase-related kinase protein family, DNA-PKcs is a member. The serine/threonine protein kinase known as DNA-Pkcs has 4,128 amino acids in its single polypeptide chain.
| Targets |
DNA-PKcs (IC50 = 91.3 nM); PI3Kγ (IC50 = 1.37 μM); ATM (IC50 = 117.93 μM)
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|---|---|
| ln Vitro |
AZD7648 inhibits IR-induced DNA-PK S2056 auto phosphoryalation with an IC50 = 92 nM in A549 non-small cell lung cancer (NSCLC) cells. DNA-PK S2056 autophosphorylation with an IC50 value of 92 nM. A significant increase in the number of cells arrested in the G2/M phase of the cell cycle, a 4-fold increase in the formation of micronuclei, and a 3-fold induction of the formation of H2AX, pATM S1981, and 53BP1 foci are all caused in A549 cells when AZD7648 (1 M) is combined with 2Gy IR for 48 hours[2].
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| ln Vivo |
AZD7648 is a potent and highly selective DNA-PK inhibitor, with good crystalline solubility, permeability and metabolic stability, good bioavailability and predictable pharmacokinetics in preclinical species, and potent knockdown of pRPA and regressions in murine xenograft models when combining with olaparib or radiation[1].
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| Cell Assay |
Cells were treated with indicated concentration of drug for 1 h.
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| References | |
| Additional Infomation |
DNA-PK inhibitor AZD7648 is an orally bioavailable ATP-competitive inhibitor of DNA-dependent protein kinase (DNA-PK), with potential chemo/radiosensitizing and antineoplastic activites. Upon oral administration, DNA-PK inhibitor AZD7648 selectively targets, binds to and inhibits the activity of DNA-PK, thereby interfering with the non-homologous end joining (NHEJ) process and preventing repair of DNA double strand breaks (DSBs) caused by ionizing radiation or chemotherapeutic treatment. This increases chemo- and radiotherapy cytotoxicity leading to enhanced tumor cell death. AZD7648 may also increase the effect of poly(ADP-ribose) polymerase (PARP) inhibitors and may work as a monotherapy in tumors with high endogenous levels of DNA damage resulting from defects in other DNA repair pathways. The enhanced ability of tumor cells to repair DSBs plays a major role in the resistance of tumor cells to chemo- and radiotherapy. DNA-PK plays a key role in the NHEJ pathway and DSB repair.
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| Molecular Formula |
C18H20N8O2
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|---|---|
| Molecular Weight |
380.4038
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| Exact Mass |
380.17
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| Elemental Analysis |
C, 56.83; H, 5.30; N, 29.46; O, 8.41
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| CAS # |
2230820-11-6
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| Related CAS # |
2230820-11-6
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| PubChem CID |
135151360
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| Appearance |
Off-white to light yellow solid powder
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| LogP |
1
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| Hydrogen Bond Donor Count |
1
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| Hydrogen Bond Acceptor Count |
7
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| Rotatable Bond Count |
3
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| Heavy Atom Count |
28
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| Complexity |
588
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| Defined Atom Stereocenter Count |
0
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| InChi Key |
XISVSTPEXYIKJL-UHFFFAOYSA-N
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| 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)
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| Chemical Name |
7-methyl-2-[(7-methyl-[1,2,4]triazolo[1,5-a]pyridin-6-yl)amino]-9-(oxan-4-yl)purin-8-one
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| Synonyms |
AZD7648; AZD 7648; AZD-7648
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| HS Tariff Code |
2934.99.9001
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| Storage |
Powder -20°C 3 years 4°C 2 years In solvent -80°C 6 months -20°C 1 month |
| Shipping Condition |
Room temperature (This product is stable at ambient temperature for a few days during ordinary shipping and time spent in Customs)
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| Solubility (In Vitro) |
DMSO: 8.3~9 mg/mL (21.9~23.7 mM)
Ethanol: ~3 mg/mL (~7.9 mM) |
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| Solubility (In Vivo) |
Solubility in Formulation 1: 10 mg/mL (26.29 mM) in 0.5% HPMC 0.1%Tween80 (add these co-solvents sequentially from left to right, and one by one), suspension solution; with sonication.
(Please use freshly prepared in vivo formulations for optimal results.) |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 2.6288 mL | 13.1441 mL | 26.2881 mL | |
| 5 mM | 0.5258 mL | 2.6288 mL | 5.2576 mL | |
| 10 mM | 0.2629 mL | 1.3144 mL | 2.6288 mL |
*Note: Please select an appropriate solvent for the preparation of stock solution based on your experiment needs. For most products, DMSO can be used for preparing stock solutions (e.g. 5 mM, 10 mM, or 20 mM concentration); some products with high aqueous solubility may be dissolved in water directly. Solubility information is available at the above Solubility Data section. Once the stock solution is prepared, aliquot it to routine usage volumes and store at -20°C or -80°C. Avoid repeated freeze and thaw cycles.
Calculation results
Working concentration： mg/mL；
Method for preparing DMSO stock solution： mg drug pre-dissolved in μL DMSO (stock solution concentration mg/mL). Please contact us first if the concentration exceeds the DMSO solubility of the batch of drug.
Method for preparing in vivo formulation:：Take μL DMSO stock solution, next add μL PEG300, mix and clarify, next addμL Tween 80, mix and clarify, next add μL ddH2O，mix and clarify.
(1) Please be sure that the solution is clear before the addition of next solvent. Dissolution methods like vortex, ultrasound or warming and heat may be used to aid dissolving.
(2) Be sure to add the solvent(s) in order.
| NCT Number | Status | Interventions | Conditions | Sponsor/Collaborators | Start Date | Phases |
| NCT03907969 | Completed | Drug: AZD7648 Drug: PLD |
Advanced Malignancies | AstraZeneca | October 9, 2019 | Phase 1 Phase 2 |
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