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Chemical Structure| 2230820-11-6 Chemical Structure| 2230820-11-6

Structure of AZD-7648
CAS No.: 2230820-11-6

Chemical Structure| 2230820-11-6

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AZD7648 is a highly potent and selective DNA-PK inhibitor with IC50 value of 92nM.

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Product Details of AZD-7648

CAS No. :2230820-11-6
Formula : C18H20N8O2
M.W : 380.40
SMILES Code : O=C1N(C)C2=CN=C(NC3=CN4C(C=C3C)=NC=N4)N=C2N1C5CCOCC5
MDL No. :MFCD32062688
InChI Key :XISVSTPEXYIKJL-UHFFFAOYSA-N
Pubchem ID :135151360

Safety of AZD-7648

GHS Pictogram:
Signal Word:Warning
Hazard Statements:H302-H315-H319-H335
Precautionary Statements:P261-P305+P351+P338

Related Pathways of AZD-7648

DNA
PI3K-AKT

Isoform Comparison

Biological Activity

In Vitro:

Cell Line
Concentration Treated Time Description References
HeLa cells 1 mM 1 hour To study the binding mode of AZD-7648 with DNA-PKcs, revealing its mechanism of competitive inhibition of ATP binding PMC8791830
A549 non-small cell lung cancer cells 0.6 nM 1 hour Evaluate the inhibitory effect of AZD7648 on DNA-PKcs autophosphorylation PMC6838110
OAW42 ovarian cancer cells 3 μM 16 hours Evaluate the effect of AZD7648 in combination with doxorubicin on DNA damage and apoptosis PMC6838110
HNSCC cell lines (FaDu, A253, Detroit 562, UMSCC12, UMSCC74A, UMSCC6) 1 µM 1-hour pretreatment AZD-7648 significantly reduced clonogenic survival of HNSCC cell lines, particularly following X-ray and proton beam therapy. DER (dose enhancement ratio) ranged from 1.41–2.86 (X-rays) and 1.63–2.52 (proton beam). PMC11169544
MC38 cells 1 μM 24 hours To evaluate the radiosensitizing effect of AZD7648 on MC38 cells. Results showed that AZD7648 at 1 μmol/L significantly enhanced IR-induced cell death, with a DEF37 of 2.02. PMC9401489
HSPCs (hematopoietic stem and progenitor cells) 7 μM 24 hours Enhance HDR editing efficiency, reduce NHEJ, and increase the conversion rate of -175T>C and -158C>T in HSPCs PMC11687217
Human airway basal stem cells (ABCs) 0.5 μM 24 hours To evaluate the effect of AZD7648 on gene insertion efficiency, results showed AZD7648 significantly improved gene insertion efficiency (from 34.8% to 61.3%) PMC11470261
UM-SCC-47 5 μM 24 hours Evaluate the radiosensitizing effect of AZD7648 on HPV+ HNSCC cells, showing significant increase in G2/M arrest and cell death. PMC10887161
CAL33 5 μM 24 hours Evaluate the radiosensitizing effect of AZD7648 on HNSCC cells, showing significant inhibition of IR-induced DNA double-strand break repair and increased cell death. PMC10887161
Cal78 1, 3, 10 µM 24 hours Pretreatment with AZD7648 significantly enhanced the inhibitory effect of X-ray and carbon ion irradiation on cell proliferation, leading to G2/M phase cell cycle arrest. PMC11173223
SW-1353 1, 3, 10 µM 24 hours Pretreatment with AZD7648 significantly enhanced the inhibitory effect of X-ray and carbon ion irradiation on cell proliferation, leading to G2/M phase cell cycle arrest. PMC11173223
HEL 50-200 µM 24-72 hours To evaluate the effect of AZD-7648 on HEL cell density and viability. Results showed IC50 between 150-200 µM after 24 hours, decreasing to 97.7 µM and 85.5 µM after 48 and 72 hours, respectively. PMC10607085
LAMA-84 100-200 µM 24-72 hours To evaluate the effect of AZD-7648 on LAMA-84 cell density and viability. Results showed IC50 values of 92.6 µM and 81.6 µM after 48 and 72 hours, respectively. PMC10607085
K-562 10-200 µM 24-72 hours To evaluate the effect of AZD-7648 on K-562 cell density and viability. Results showed that IC50 was not reached (IC50 > 200 µM) within the tested concentration range. PMC10607085
Primary human CD4+ T cells 1 µM 3 days Evaluate the effect of AZD7648 on CRISPR/Cas9-mediated HDR-KI efficiency, results showed significant increase in HDR-KI efficiency PMC10425386
HiPSC 1 µM 3 days Evaluate the effect of AZD7648 on CRISPR/Cas9-mediated HDR-KI efficiency, results showed significant increase in HDR-KI efficiency PMC10425386
HepG2 1 µM 3 days Evaluate the effect of AZD7648 on CRISPR/Cas9-mediated HDR-KI efficiency, results showed significant increase in HDR-KI efficiency PMC10425386
Jurkat 1 µM 3 days Evaluate the effect of AZD7648 on CRISPR/Cas9-mediated HDR-KI efficiency, results showed significant increase in HDR-KI efficiency PMC10425386
HEK293T 1 µM 3 days Evaluate the effect of AZD7648 on CRISPR/Cas9-mediated HDR-KI efficiency, results showed significant increase in HDR-KI efficiency PMC10425386
Mature B-cell lines (3301015, 5680001) 1-20 μM 3 days Evaluate AZD7648 effects on normal B-cell viability; results showed AZD7648 decreased viability of one or both B-cell lines at 1-20μM PMC10111164
B-ALL cell lines (LAX56, BLQ5, LAX7R) 1-20 μM 3 days Evaluate AZD7648 effects on B-ALL cell viability; results showed AZD7648 decreased viability at all tested concentrations PMC10111164
MG63 cells 10 µM 48 hours Evaluate the synergistic effect of AZD-7648 with DOX, results showed AZD-7648 significantly enhanced the inhibitory effect of DOX on osteosarcoma cells. PMC11372366
U2OS cells 10 µM 48 hours Evaluate the synergistic effect of AZD-7648 with DOX, results showed AZD-7648 significantly enhanced the inhibitory effect of DOX on osteosarcoma cells. PMC11372366
HOS cells 10 µM 48 hours Evaluate the synergistic effect of AZD-7648 with DOX, results showed AZD-7648 significantly enhanced the inhibitory effect of DOX on osteosarcoma cells. PMC11372366
143B cells 10 µM 48 hours Evaluate the synergistic effect of AZD-7648 with DOX, results showed AZD-7648 significantly enhanced the inhibitory effect of DOX on osteosarcoma cells. PMC11372366
Primary human hematopoietic stem and progenitor cells (HSPCs) 0.5 µM 48 hours Improving homology-directed repair (HDR) efficiency, achieving mean editing efficiency of 97% PMC11147503
Healthy fibroblasts (SBLF8, SBLF9) 5000 nM 48 hours AZD7648 alone had minimal toxicity to healthy fibroblasts, but combined with ionizing radiation reduced clonogenic survival PMC11172136
HNSCC cell lines (Cal33) 5000 nM 48 hours AZD7648 combined with ionizing radiation significantly increased cell death with supra-additive effects PMC11172136
B2M gene-targeted CD34+ HSPCs 0.33, 1, and 3 μM 48 hours To evaluate the effect of AZD7648 on NHEJ and HDR, results showed AZD7648 inhibited NHEJ and promoted HDR. PMC11863497
CD34+ hematopoietic stem and progenitor cells (HSPCs) 0.33, 1, and 3 μM 48 hours To evaluate the effect of AZD7648 on HDR efficiency, results showed AZD7648 significantly increased HDR efficiency. PMC11863497
KG-1 100-200 µM 48-72 hours To evaluate the effect of AZD-7648 on KG-1 cell density and viability. Results showed IC50 of 159.9 µM after 72 hours. PMC10607085
GOT1 1 μM 5 days To evaluate the effect of AZD7648 on PRRT-induced cell death, results showed that AZD7648 significantly increased PRRT-induced cell death. PMC10283055
NCI-H69 1 μM 7 days To evaluate the effect of AZD7648 on the viability of PRRT-treated cells, results showed that AZD7648 significantly reduced the viability of PRRT-treated cells. PMC10283055
BON1-SSTR2 1 μM 7 days To evaluate the effect of AZD7648 on the viability of PRRT-treated cells, results showed that AZD7648 significantly reduced the viability of PRRT-treated cells. PMC10283055
EW8 cells 0.1 μM 72 hours AZD-7648 synergized with etoposide, significantly reducing cell viability and proliferation PMC11293986
TC-32 cells 0.1 μM 72 hours AZD-7648 synergized with etoposide, significantly reducing cell viability and proliferation PMC11293986
FaDu head and neck cancer cells 0.6 μM 72 hours Evaluate the effect of AZD7648 in combination with olaparib on genomic instability and apoptosis in ATM-deficient cells PMC6838110
VMCUB-1 0.01–20 μM 72 hours To evaluate the radiosensitizing effect of AZD7648 on bladder cancer cells, results showed a decrease in IC50 values with increasing radiation doses PMC9220184
J82 0.01–20 μM 72 hours To evaluate the radiosensitizing effect of AZD7648 on bladder cancer cells, results showed a decrease in IC50 values with increasing radiation doses PMC9220184
SCaBER 0.01–20 μM 72 hours To evaluate the radiosensitizing effect of AZD7648 on bladder cancer cells, results showed a decrease in IC50 values with increasing radiation doses PMC9220184

In Vivo:

Species
Animal Model
Administration Dosage Frequency Description References
NBSGW mice Immune-deficient mouse model Transplant after in vitro treatment 0.3 μM 16 weeks To evaluate the effect of AZD7648 on long-term engraftment of HDR-edited HSPCs, results showed AZD7648 significantly increased the long-term engraftment of HDR-edited cells. PMC11863497
Nude mice A549 xenograft model Oral 100 mg/kg Once daily for 21 days Evaluate the tumor growth inhibitory effect of AZD7648 in combination with radiotherapy PMC6838110
Rj:NMRI-Foxn1nu/nu mice BON1-SSTR2 and NCI-H69 xenograft models Oral gavage 50 mg/kg or 100 mg/kg Once daily for 7 consecutive days To evaluate the enhancement of PRRT anti-tumor effects by AZD7648, results showed that AZD7648 significantly enhanced the anti-tumor effects of PRRT. PMC10283055
NBSGW mice Β-thalassemia and sickle cell disease model Tail vein injection 7 μM Single administration, observed for 16-18 weeks Enhance HDR editing efficiency, reduce NHEJ, increase the conversion rate of -175T>C and -158C>T in HSPCs, and produce functional HbF in vivo PMC11687217
BALB/c nude mice Subcutaneous xenograft model Oral 70 mg/kg Once daily for 14 days Evaluate the synergistic effect of AZD-7648 with DOX, results showed the combination therapy significantly inhibited osteosarcoma growth. PMC11372366
Mice MC38, CT26, and B16-F10 syngeneic tumor models Oral 75 mg/kg Once daily for 5 days To evaluate the antitumor efficacy of AZD7648 in combination with RT. Results showed that the combination of AZD7648 and RT significantly improved tumor control, with complete tumor regressions observed in 75% and 42% of mice in MC38 and CT26 models, respectively. PMC9401489
Nude mice TC-32 and EW8 orthotopic xenograft models AZD-7648 orally, etoposide intraperitoneally AZD-7648 25 mg/kg BID, etoposide 10 mg/kg daily Daily for 5 days, repeated every 2 weeks Combination of AZD-7648 and etoposide led to tumor shrinkage, enhanced DNA damage and apoptosis PMC11293986

Protocol

Bio Calculators
Preparing Stock Solutions 1mg 5mg 10mg

1 mM

5 mM

10 mM

2.63mL

0.53mL

0.26mL

13.14mL

2.63mL

1.31mL

26.29mL

5.26mL

2.63mL

Dissolving Methods
The prepared working fluid is recommended to be prepared now and used up as soon as possible in a short period of time. The percentage shown in front of the following solvent refers to the volume ratio of the solvent in the final solution; If precipitation or precipitation occurs in the preparation process, it can be assisted by heating and/or ultrasound.
Protocol 1
 

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