NU7026

Catalog No.S2893 Batch:S289303

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Technical Data

Formula

C17H15NO3

Molecular Weight 281.31 CAS No. 154447-35-5
Solubility (25°C)* In vitro DMSO 2 mg/mL (7.1 mM)
Water Insoluble
Ethanol Insoluble
* <1 mg/ml means slightly soluble or insoluble.
* 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.
* Room temperature shipping (Stability testing shows this product can be shipped without any cooling measures.)

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Biological Activity

Description NU7026 (LY293646) 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. NU7026 enhances G2/M cell arrest and apoptosis.
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 doxorubicin, mAMSA with PF50 values ranging from approximately 19 for mAMSA to approximately 2 in K562 cells. NU7026 (10 μM) also potentiates the growth inhibitory effect in this leukemia cell line with a PF50 value of 10.53. NU7026 (10 μM) enhances the -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) has synergistic cytotoxic activity at nontoxic doses of NU7026 in a CLL cell line (I83) and in primary CLL-lymphocytes. NU7026 (10 μM) increases -induced G(2)/M arrest in I83 cells. NU7026 (10 μM) enhances -induced γH2AX throughout the cell cycle in the I83 cell line. NU7026 (10 μM) Increases -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]

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 (from reference)

Kinase Assay:

[1]

  • Recombinant kinase assay

    Mammalian DNA-PK (500 ng/μL) is isolated from HeLa cell nuclear extract after chromatography using Q-Sepharose, S-Sepharose, and Heparin agarose. DNA-PK (250 ng) activity is measured at 30℃, in a final volume of 40 μL, in buffer containing 25 mM HEPES (pH 7.4), 12.5 mM MgCl2, 50 mM KCl, 1 mM DTT, 10% v/v Glycerol, 0.1% w/v NP-40, and 1 mg of the substrate GST-p53N66 in polypropylene 96-well plates. To the assay mix, varying concentrations of NU7026 (in DMSO at a final concentration of 1% v/v) are added. After 10 min of incubation, ATP is added to give a final concentration of 50 μM, along with a 30-mer double-stranded DNA oligonucleotide (final concentration of 0.5 ng/mL), to initiate the reaction. After 1 hour with shaking, 150 μL of PBS are added to the reaction, and 5 μL are then transferred to a 96-well opaque white plate containing 45 μl of PBS per well, where the GSTp53N66 substrate is allowed to bind to the wells for 1 hour. The IC50s for the compounds in all of the enzymes assays are derived from sigmoidal plots using the graphic package Prism, in which the enzyme activity in the varying concentration of compounds is plotted against the concentration of compound.

Cell Assay:

[6]

  • Cell lines

    A549 cells

  • Concentrations

    10 μM

  • Incubation Time

    3 h

  • Method

    Cells were treated with indicated concentration of drug for 3 h.

Animal Study:

[3]

  • Animal Models

    Female BALB/c mice

  • Dosages

    25 mg/kg

  • Administration

    intraperitoneal injection or orally

Customer Product Validation

Data from [Nucleic Acids Res, 2013, 41(15), 7378-86]

Data from [Data independently produced by , , Clin Cancer Res, 2014, 20(13): 3496-50]

Data from [Data independently produced by , , Nucleic Acids Res, 2016, 44(21):10259-10276]

Data from [Data independently produced by , , Oncotarget, 2016, 7(25):38367-38379]

Selleck's NU7026 has been cited by 63 publications

LC3B drives transcription-associated homologous recombination via direct interaction with R-loops [ Nucleic Acids Res, 2024, gkae156] PubMed: 38412240
Generation and characterization of six human induced pluripotent stem cell lines (hiPSCs) from three individuals with SSADH Deficiency and CRISPR-corrected isogenic controls [ Stem Cell Res, 2024, 77:103424] PubMed: 38677032
Topoisomerase I is an Evolutionarily Conserved Key Regulator for Satellite DNA Transcription [ bioRxiv, 2024, 2024.05.03.592391] PubMed: 38746280
Blocking Genomic Instability Prevents Acquired Resistance to MAPK Inhibitor Therapy in Melanoma [ Cancer Discov, 2023, 13(4):880-909] PubMed: 36700848
Blocking Genomic Instability Prevents Acquired Resistance to MAPK Inhibitor Therapy in Melanoma [ Cancer Discov, 2023, 13(4):880-909] PubMed: 36700848
ABL1 kinase as a tumor suppressor in AML1-ETO and NUP98-PMX1 leukemias [ Blood Cancer J, 2023, 13(1):42] PubMed: 36959186
A function for ataxia telangiectasia and Rad3-related (ATR-kinase in cytokinetic abscission. [ iScience, 2023, 25(7)] PubMed: None
The fatty liver disease-causing protein PNPLA3-I148M alters lipid droplet-Golgi dynamics [ bioRxiv, 2023, 2023.10.13.562302] PubMed: 37873239
DNA-PK promotes activation of the survival kinase AKT in response to DNA damage through an mTORC2-ECT2 pathway [ Sci Signal, 2022, 15(715):eabh2290] PubMed: 34982576
A function for ataxia telangiectasia and Rad3-related (ATR) kinase in cytokinetic abscission [ iScience, 2022, 25(7):104536] PubMed: 35754741

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SHIPPING AND STORAGE
Selleck products are transported at room temperature. If you receive the product at room temperature, please rest assured, the Selleck Quality Inspection Department has conducted experiments to verify that the normal temperature placement of one month will not affect the biological activity of powder products. After collecting, please store the product according to the requirements described in the datasheet. Most Selleck products are stable under the recommended conditions.

NOT FOR HUMAN, VETERINARY DIAGNOSTIC OR THERAPEUTIC USE.