Home DNA Damage/DNA Repair DNA-PK inhibitor NU7026

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NU7026 DNA-PK inhibitor

Cat.No.S2893

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. This compound enhances G2/M cell arrest and apoptosis.
NU7026 DNA-PK inhibitor Chemical Structure

Chemical Structure

Molecular Weight: 281.31

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Quality Control

Batch: Purity: 99.94%
99.94

Cell Culture, Treatment & Working Concentration

Cell Lines Assay Type Concentration Incubation Time Formulation Activity Description PMID
HeLa cells Function assay Inhibition of DNA dependent protein kinase isolated from HeLa cells, IC50=0.23 μM 15658870
HeLa cells Function assay Inhibition of mTOR protein isolated from HeLa cells, IC50=6.4 μM 15658870
HeLa Function assay In vitro inhibition of DNA-dependent protein kinase(DNA-PK) from HeLa (human carcinoma) cells, IC50=0.23μM 12941339
Click to View More Cell Line Experimental Data

Solubility

In vitro
Batch:

4-Methylpyridine : 5 mg/mL

DMSO : 1 mg/mL (3.55 mM)
(Moisture-contaminated DMSO may reduce solubility. Use fresh, anhydrous DMSO.)

Water : Insoluble

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In vivo
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Method for preparing in vivo formulation: Take μL DMSO master liquid, next add μL Corn oil, mix and clarify.

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Chemical Information, Storage & Stability

Molecular Weight 281.31 Formula

C17H15NO3

 Storage (From the date of receipt)
CAS No. 154447-35-5 Download SDF Storage of Stock Solutions

Synonyms LY293646 Smiles C1COCCN1C2=CC(=O)C3=C(O2)C4=CC=CC=C4C=C3

Mechanism of Action

Targets/IC50/Ki
DNA-PK
(Cell-free assay)
0.23 μM
PI3K
(Cell-free assay)
13 μM
In vitro

NU7026 potentiates ionizing radiation induced cytotoxicity in a concentration-dependent manner in V3YAC and PARP-1+/+ cells. This compound completely abolishes potentially lethal damage recovery in growth-arrested cells. It inhibits DNA DSB repair by 56% in the V3YAC cell line.

This chemical (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. It (10 μM) also potentiates the growth inhibitory effect in this leukemia cell line with a PF50 value of 10.53. This compound (10 μM) enhances the -induced cell cycle G2 blockade in K562 cells. It potentiates topo II poisons involves inhibition of nonhomologous end joining and a G2/M checkpoint arrest.

This compound (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.

It (< 10 μM) has synergistic cytotoxic activity at nontoxic doses of this chemical in a CLL cell line (I83) and in primary CLL-lymphocytes. This compound (10 μM) increases -induced G(2)/M arrest in I83 cells. It (10 μM) enhances -induced γH2AX throughout the cell cycle in the I83 cell line. This chemical (10 μM) Increases -Induced apoptosis in the I83 cell line.

It (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.

Kinase Assay
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 this compound (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.
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 this compound at dose of 20 mg/kg is 20 and 15%, respectively.

References
  • [4] https://pubmed.ncbi.nlm.nih.gov/17351105/
  • [5] https://pubmed.ncbi.nlm.nih.gov/19244120/
  • [6] https://pubmed.ncbi.nlm.nih.gov/36280132/

Applications

Methods Biomarkers Images PMID
Western blot pDNA-PKcs S2056 / DNA-PKcs
S2893-WB1
22131882
Growth inhibition assay Cell viability
S2893-viability1
26716839

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