AZD-7648

本公司产品仅用于科研实验，不得用于人体或动物的临床与诊断

AZD-7648 是一种 DNA 依赖性蛋白激酶 (DNA-PK) 抑制剂，酶测定中 IC50 为 0.63 nM，具有抗肿瘤活性。

AZD-7648 is an inhibitor of DNA-dependent protein kinase (DNA-PK) with the?IC50 of 0.63 nM in an enzyme assayhas anti-tumor activity.(In Vitro):AZD7648 (0-30 μM) is a potent radiosensitizer.AZD7648 (3 μM) increases sensitivity to doxorubicin.AZD7648 (0.6 μM) enhances the activity of PARP inhibitor olaparib.(In Vivo):AZD-7648 (100 mg/kg; p.o.; once daily for 5 days) induces tumour growth inhibition and tumour regression.

AZD7648 (0-30 μM) is a potent radiosensitizer.AZD7648 (3 μM) increases sensitivity to doxorubicin.AZD7648 (0.6 μM) enhances the activity of PARP inhibitor olaparib. Western Blot Analysis Cell Line:IR (ionizing radiation)-treated A549 cells or OAW42 cells treated with doxorubicinConcentration:0.03, 0.1, 0.3, 1, 3, 10 and 30 μM for A549; 3 μM for OAW42 Incubation Time:1 h for A549; 0.5, 2, 4, 8 and 16 h for OAW42 Result:Potently inhibited DNA-PKcs autophosphorylation at Ser2056. Downregulated pDNA-PKcs Ser2056, γH2AX Ser139 and pRPA32 Ser4/Ser8 phosphorylation at early time points (at 30?min, 2?h and 4?h). Resulted in increased levels of γH2AX and the apoptosis marker cleaved PARP1 compared with doxorubicin treatment alone at later time points (8 and 16?h).Cell Cycle Analysis Cell Line:IR (ionizing radiation)-treated A549 cells or A549 cells Concentration:0-30 μM Incubation Time:48 hResult:Arrested cell cycle at G2/M phase.

AZD-7648 (100 mg/kg; p.o.; once daily for 5 days) induces tumour growth inhibition and tumour regression. Animal Model:Nude mice, A549 xenografts and NCI-H1299 xenografts Dosage:100 mg/kg Administration:Oral administration, once daily for 5 days Result:Induced tumour growth inhibition in combination with IR in A549 xenografts and induced tumour regression in combination with IR in NCI-H1299 xenografts.

——

Cell Cycle/DNA Damage

DNA-PK

DNA-PK

Cancer

Solid tumours

2230820-11-6

380.4

C18H20N8O2

>98% (HPLC)

DMSO:5 mg/mL (13.14 mM)

Cc1cc2ncnn2cc1Nc1ncc2n(C)c(=O)n(C3CCOCC3)c2n1

7-methyl-2-((7-methyl-[124]triazolo[15-a]pyridin-6-yl)amino)-9-(tetrahydro-2H-pyran-4-yl)-79-dihydro-8H-purin-8-one

(-20℃)

With Ice Pack

≥ 2 years