NU7026

Catalog No.S2893 Synonyms: LY293646

NU7026 Chemical Structure

Molecular Weight(MW): 281.31

NU7026 is a potent DNA-PK inhibitor with IC50 of 0.23 μM in cell-free assays, 60-fold selective for DNA-PK than PI3K and inactive against both ATM and ATR.

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5 Customer Reviews

  • M059K cells were transfected with Scrambled, ERCC1, EGFR, or EGFR–ERCC1 siRNA. Following 48 hours of siRNA transfection, Scrambled siRNA and ERCC1 siRNA-transfected cells were treated with 1 µmol/L gefitinib or 125 nMol/L NU7026, or both, while EGFR siRNA and EGFR–ERCC1 siRNA-transfected cells were treated with 125 nMol/L of NU7026 1 hour prior 4 Gy IR treatment. Survival of these cells was then assessed 72 hours following IR treatment via MTT assay.

    Clin Cancer Res, 2014, 20(13): 3496-50. NU7026 purchased from Selleck.

    (B) Effect of DNA-PK inhibition on N-OH-PhIP-induced DDR. Cells were treated with N-OH-PhIP (10 μM) with or without DNA-PK inhibitor (DNA-PKi) NU7026 for 14 h. Samples were then subjected to SDS-PAGE and western blot analysis was performed as indicated. Hsp90 was used as loading control.

    Nucleic Acids Res, 2016, 44(21):10259-10276. NU7026 purchased from Selleck.

  • DNA damage-induced inhibition of rRNA synthesis is dependent on DNA-PK and PARP-1 activity. Representative nuclei stained by EU are shown 22 h after 2 h treatment with 25 µg/ml cisplatin. Cells were treated with cisplatin under the following conditions: pretreatment with Nu7026 (Nu7026, 26) or Nu7441 (Nu7441, 41)

    Nucleic Acids Res 2013 41(15), 7378-86. NU7026 purchased from Selleck.

    (B) CLL cells were subjected to UV-C light (30 J/m2) (left panel) or IR at a dose of 5 Gy (right panel) and immediately incubated in the absence or presence of 3 μM APC or 10 μM NU7026. γH2AX was analyzed by flow cytometry at the indicated times and expressed as fold change (UV) or as % of the value at time 0 (IR). In all panels, results are means ± SEM of 3–5 independent experiments. Significance relative to the absence of APC (shown at the last incubation time) was analyzed by two-way Anova followed by Bonferroni post-test: **P < 0.01; ****P < 0.0001.

    Oncotarget, 2016, 7(25):38367-38379. NU7026 purchased from Selleck.

  • In vitro selectivity study of [18F]FMTA-2. ZSTK474 (ATP-competitive PI3K inhibitor), GDC-0941 (ATP-competitive PI3K inhibitor), Akt 1/2 inhibitor, PIK-75 (allosteric PI3K inhibitor), NU7441 (DNA-PK inhibitor), NU7026 (DNA-PK inhibitor), KU-55933 (ATM kinase inhibitor), AZ20 (ATR kinase inhibitor), ETP-46464 (ATR kinase inhibitor) and KU0063794 (mTOR inhibitor), respectively (n = 3–6, *P b 0.05, **P < 0.01 vs. control, Mann-Whitney U test). Kinase inhibitors (0.5 μM) were co-incubated with [18F]FMTA-2 (0.15 MBq/mL).

    Nucl Med Biol, 2016, 43(1):101-7. NU7026 purchased from Selleck.

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Biological Activity

Description NU7026 is a potent DNA-PK inhibitor with IC50 of 0.23 μM in cell-free assays, 60-fold selective for DNA-PK than PI3K and inactive against both ATM and ATR.
Targets
DNA-PK [1]
(Cell-free assay)
PI3K [1]
(Cell-free assay)
0.23 μM 13 μM
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. [1] 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. [2] 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. [3] 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. [4] 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. [5]

Cell Data
Cell Lines Assay Type Concentration Incubation Time Formulation Activity Description PMID
HeLa cells NWjnR3FyTnWwY4Tpc44h[XO|YYm= M1Li[GlvcGmkaYTpc44hd2ZiRF7BJIRmeGWwZHXueEBxem:2ZXnuJItqdmG|ZTDpd49t[XSnZDDmdo9uKEinTHGgZ4VtdHNuIFnDOVA:OC5{MzFOwG0> MnHLNVU3PTh6N{C=
HeLa cells MkD2SpVv[3Srb36gZZN{[Xl? M37pPGlvcGmkaYTpc44hd2ZibWTPVkBxem:2ZXnuJIl{d2yjdHXkJIZzd21iSHXMZUBk\WyuczygTWM2OD14LkSg{txO M{Ltb|E2PjV6OEew

... Click to View More Cell Line Experimental Data

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. [3]

Protocol

Animal Research:[3]
+ Expand
  • Animal Models: Female BALB/c mice
  • Formulation: 10% DMSO and 5% Tween 20 in saline
  • Dosages: 25 mg/kg
  • Administration: intraperitoneal injection or orally
    (Only for Reference)

Solubility (25°C)

In vitro DMSO 1 mg/mL (3.55 mM)
Water Insoluble
Ethanol Insoluble
In vivo Add solvents individually and in order:
1% DMSO+30% polyethylene glycol+1% Tween 80
30 mg/mL

* Please note that Selleck tests the solubility of all compounds in-house, and the actual solubility may differ slightly from published values. This is normal and is due to slight batch-to-batch variations.

Chemical Information

Molecular Weight 281.31
Formula

C17H15NO3

CAS No. 154447-35-5
Storage powder
Synonyms LY293646

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Tech Support

Answers to questions you may have can be found in the inhibitor handling instructions. Topics include how to prepare stock solutions, how to store inhibitors, and issues that need special attention for cell-based assays and animal experiments.

Handling Instructions

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Cell Lines Assay Type Concentration Incubation Time Formulation Activity Description PMID