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NU7026

Cat No.
CEI-0878
Description
NU7026 is a potent DNA-PK inhibitor with IC50 of 0.23 μM, 60-fold selective for DNA-PK than PI3K and inactive against both ATM and ATR.
CAS No.
154447-35-5
Molecular Weight
281.31
Storage
2 years -20 centigrade Powder; 2 weeks 4 centigrade in DMSO; 6 months -80 centigrade in DMSO.
Targets
DNA-PK, PI3K
IC50
0.23 μM; 13 μM
Molecular Formula
C17H15NO3
Chemical Name
4H-Naphtho[1,2-b]pyran-4-one, 2-(4-morpholinyl)-
Solubility
DMSO 1 mg/mL; Water <1 mg/mL; Ethanol <1 mg/mL
In vitro
NU7026 potentiates ionizing radiation induced cytotoxicity in a concentration-dependent manner in V3YAC and PARP-1+/+ cells. NU7026 completely abolishes potentially lethal damage recovery in growth-arrested cells. NU7026 inhibits DNA DSB repair by 56% in the V3YAC cell line. NU7026 (10 μM) potentiates the growth inhibitory effects of idarubicin, daunorubicin, doxorubicin, etoposide, mAMSA, and mitoxantrone with PF50 values ranging from approximately 19 for mAMSA to approximately 2 for idarubicin in K562 cells. NU7026 (10 μM) also potentiates the growth inhibitory effect of etoposide in this leukemia cell line with a PF50 value of 10.53. NU7026 (10 μM) enhances the etoposide-induced cell cycle G2 blockade in K562 cells. NU7026 potentiates topo II poisons involves inhibition of nonhomologous end joining and a G2/M checkpoint arrest.NU7026 (10 μM) exposure of 4 h in combination with 3 Gy radiation is required for a significant radiosensitisation effect in CH1 human ovarian cancer cells.NU7026 (< 10 μM) plus chlorambucil has synergistic cytotoxic activity at nontoxic doses of NU7026 in a CLL cell line (I83) and in primary CLL-lymphocytes. NU7026 (10 μM) increases chlorambucil-induced G(2)/M arrest in I83 cells. NU7026 (10 μM) enhances chlorambucil -induced γH2AX throughout the cell cycle in the I83 cell line. NU7026 (10 μM) Increases chlorambucil-Induced apoptosis in the I83 cell line.NU7026 (55 μM) results in a dramatic induction of telomere fusion in p53 null MEFs and significantly fewer telomere fusions in p53 and ligase IV double null MEFs.
In vivo
NU7026 (20mg/kg, i.v.) undergoes rapid plasma clearance (0.108/hour) in mice and this is largely attributed to extensive metabolism. Bioavailability following interperitoneal (i.p.) and p.o. administration of NU7026 at dose of 20 mg/kg is 20 and 15%, respectively.
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