NU7026
NU7026 structure
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Common Name | NU7026 | ||
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| CAS Number | 154447-35-5 | Molecular Weight | 281.306 | |
| Density | 1.3±0.1 g/cm3 | Boiling Point | 459.9±45.0 °C at 760 mmHg | |
| Molecular Formula | C17H15NO3 | Melting Point | N/A | |
| MSDS | Chinese USA | Flash Point | 231.9±28.7 °C | |
Use of NU7026NU 7026 is a novel specific DNA-PK inhibitor with IC50 of 0.23±0.01 μM, also inhibits PI3K with IC50 of 13±3 μM. |
This table lists Chinese names, IUPAC names and various aliases of this chemical substance.
| Name | 2-morpholin-4-ylbenzo[h]chromen-4-one |
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| Synonym | More Synonyms |
This table contains bioactivity, target information and biological‑assay experimental data of this compound.
| Description | NU 7026 is a novel specific DNA-PK inhibitor with IC50 of 0.23±0.01 μM, also inhibits PI3K with IC50 of 13±3 μM. |
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| Related Catalog | |
| Target |
DNA-PK:0.23 μM (IC50) PI3K:13 μM (IC50) |
| In Vitro | NU7026 (10 μM) potentiates ionizing radiation (IR) cytotoxicity [potentiation factor at 90% cell kill (PF90)=1.51±0.04] in exponentially growing DNA-PK proficient but not deficient cells[1]. NU7026 synergistically sensitizes I83 cells to Chlorambucil (CLB) 3.5-fold[2].NU7026, a novel inhibitor of the DNA repair enzyme DNA-dependent protein kinase (DNA-PK). At a dose of 10 μM, which is nontoxic to cells per se, a minimum NU7026 exposure of 4 h in combination with 3 Gy radiation is required for a significant radiosensitisation effect in CH1 human ovarian cancer cells[3]. |
| In Vivo | NU7026, a novel inhibitor of the DNA repair enzyme DNA-dependent protein kinase (DNA-PK). Following intravenous administration to mice at 5 mg/kg, NU7026 underwent rapid plasma clearance (0.108 L/h) and this is largely attributed to extensive metabolism. Bioavailability following interperitoneal (i.p.) and p.o. administration at 20 mg/kg is 20 and 15%, respectively[3]. |
| 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°C, 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 (the NH2-terminal 66 amino acid residues of human wild-type p53 fused to glutathione S-transferase) in polypropylene 96-well plates. To the assay mix, varying concentrations of inhibitor (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 h 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 h. To detect the phosphorylation event on the serine 15 residue of p53 elicited by DNA-PK, a p53 phosphoserine-15 antibody is used in a basic ELISA procedure. An antirabbit horseradish peroxidase-conjugated secondary antibody is then used in the ELISA before the addition of chemiluminescence reagent to detect the signal as measured by chemiluminescent counting via a TopCount NXT[1]. |
| Cell Assay | I83 cells are plated in RPMI 1640 medium with 10% FBS (1.5×105 cells/mL) and treated with vehicle (DMSO), 5 μM CLB, CLB IC50, 10 μM NU7026, or the combination of both drugs for 0, 6, 24, and 48 h. Cell cycle distribution, apoptosis, DNA-PK phosphorylation, and γH2AX determination are determined, and they are expressed as a percentage of cells in each phase of the cycle. DNA content is analyzed with a FACSCalibur flow cytometer equipped with CellQuest software[2]. |
| Animal Admin | Mice[3] Female BALB/c mice are used. NU7026 is formulated in 10% DMSO and 5% Tween 20 in saline for i.p. and perorally (p.o.) administration at 20 and 50 mg/kg, respectively. For i.v. dosing at 5 mg/kg, NU7026 is formulated in 10% ethanol, 25% PEG 200 and 5% Tween 20 in saline. Control animals receive the vehicle alone. Groups of three mice are injected per time point. Blood is collected by cardiac puncture following transient anaesthesia with halothane at 0.083, 0.25, 0.5, 1, 2, 4, 6, and 24 h post administration. Following centrifugation at 1500 g for 2 min to obtain plasma, samples are stored at −20°C until analysis. For urinary excretion studies, NU7026 is administered at 5 mg/kg i.v. Urine is collected over 24 h in metabolic cages, and stored at −20°C until required. |
| References |
This table shows physicochemical parameters including melting point, boiling point, density, solubility and optical rotation. Missing data is marked as N/A.
| Density | 1.3±0.1 g/cm3 |
|---|---|
| Boiling Point | 459.9±45.0 °C at 760 mmHg |
| Molecular Formula | C17H15NO3 |
| Molecular Weight | 281.306 |
| Flash Point | 231.9±28.7 °C |
| Exact Mass | 281.105194 |
| PSA | 42.68000 |
| LogP | 3.29 |
| Appearance of Characters | solid | tan |
| Vapour Pressure | 0.0±1.1 mmHg at 25°C |
| Index of Refraction | 1.673 |
| InChIKey | KKTZALUTXUZPSN-UHFFFAOYSA-N |
| SMILES | O=c1cc(N2CCOCC2)oc2c1ccc1ccccc12 |
| Storage condition | 2-8°C |
| Water Solubility | DMSO: 3 mg/mL at 60 °C, soluble |
This table provides MSDS information including hazard classification, first‑aid, fire‑fighting, spill handling, operation and storage instructions.
This table covers safety warnings, protective measures, incompatible substances and disposal guidelines for this compound.
| Personal Protective Equipment | Eyeshields;Gloves;type N95 (US);type P1 (EN143) respirator filter |
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| Hazard Codes | Xi |
| RIDADR | NONH for all modes of transport |
| WGK Germany | 3 |
This table presents publicly reported synthetic routes, reaction conditions, reactants and product information of the compound.
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~63%
NU7026 CAS#:154447-35-5 |
| Literature: Griffin, Roger J.; Fontana, Gabriele; Golding, Bernard T.; Guiard, Sophie; Hardcastle, Ian R.; Leahy, Justin J. J.; Martin, Niall; Richardson, Caroline; Rigoreau, Laurent; Stockley, Martin; Smith, Graeme C. M. Journal of Medicinal Chemistry, 2005 , vol. 48, # 2 p. 569 - 585 |
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~%
NU7026 CAS#:154447-35-5 |
| Literature: Journal of Medicinal Chemistry, , vol. 48, # 2 p. 569 - 585 |
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~%
NU7026 CAS#:154447-35-5 |
| Literature: Journal of Medicinal Chemistry, , vol. 48, # 2 p. 569 - 585 |
This table lists upstream starting materials and downstream derivative products related to this chemical.
| Precursor 3 | |
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| DownStream 0 | |
This table lists relevant public references with title, journal and publication metadata for this compound.
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DNA double-strand breaks by Cr(VI) are targeted to euchromatin and cause ATR-dependent phosphorylation of histone H2AX and its ubiquitination.
Toxicol. Sci. 143(1) , 54-63, (2014) Hexavalent chromium is a human respiratory carcinogen that undergoes intracellular activation in vivo primarily via reduction with ascorbate. Replication of Cr-adducted DNA triggers mismatch repair th... |
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Effects of topoisomerase inhibitors that induce DNA damage response on glucose metabolism and PI3K/Akt/mTOR signaling in multiple myeloma cells.
Am. J. Cancer Res. 5 , 1649-64, (2015) Hallmarks of cancer cells comprise altered glucose metabolism (aerobic glycolysis) and differences in DNA damage response (DDR). Glucose transporters (GLUT), glycolytic enzymes such as hexokinase (HK)... |
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DNA-dependent protein kinase catalytic subunit inhibitor reverses acquired radioresistance in lung adenocarcinoma by suppressing DNA repair.
Mol. Med. Report. 12 , 1328-34, (2015) The mechanisms underlying lung cancer radioresistance remain to be fully elucidated. The DNA repair pathway is a predominant target of radiotherapy, which is considered to be involved in the acquired ... |
This table contains target information, in‑vitro & in‑vivo assay data for this compound.
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Name: Tocris HTS for Inhibitors of Aerobactin Synthetase lucA
Source: 23265
External Id: IucA Pilot Assay Tocris Library
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Name: Inhibition of DNA dependent protein kinase isolated from HeLa cells
Source: ChEMBL
Target: DNA-dependent protein kinase catalytic subunit
External Id: CHEMBL827974
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Name: Delta TM value showing the stabilisation of CAMK2G produced by compound binding
Source: ChEMBL
Target: Calcium/calmodulin-dependent protein kinase type II subunit gamma
External Id: CHEMBL3430795
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Name: Delta TM value showing the stabilisation of CAMK4 produced by compound binding
Source: ChEMBL
Target: Calcium/calmodulin-dependent protein kinase type IV
External Id: CHEMBL3430796
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Name: Delta TM value showing the stabilisation of CAMK2B produced by compound binding
Source: ChEMBL
Target: Calcium/calmodulin-dependent protein kinase type II subunit beta
External Id: CHEMBL3430793
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Name: Delta TM value showing the stabilisation of CAMK2D produced by compound binding
Source: ChEMBL
Target: Calcium/calmodulin-dependent protein kinase type II subunit delta
External Id: CHEMBL3430794
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Name: Delta TM value showing the stabilisation of CDK6 produced by compound binding
Source: ChEMBL
Target: Cyclin-dependent kinase 6
External Id: CHEMBL3430799
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Name: Delta TM value showing the stabilisation of CDKL1 produced by compound binding
Source: ChEMBL
Target: Cyclin-dependent kinase-like 1
External Id: CHEMBL3430800
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Name: Delta TM value showing the stabilisation of CAMKK2 produced by compound binding
Source: ChEMBL
Target: Calcium/calmodulin-dependent protein kinase kinase 2
External Id: CHEMBL3430797
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Name: Delta TM value showing the stabilisation of CDK2 produced by compound binding
Source: ChEMBL
Target: Cyclin-dependent kinase 2
External Id: CHEMBL3430798
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This table collects all English aliases, systematic names and CAS‑related synonyms of the compound.
| 2-(Morpholin-4-yl)-benzo[h]chromen-4-one |
| NU7026 |
| 2-(4-Morpholinyl)-4H-benzo[h]chromen-4-one |
| DNA-Dependent Protein Kinase Inhibitor II |
| 2-(Morpholin-4-yl)-4H-benzo[h]chromen-4-one |
| DNA-PK Inhibitor II |
| 2-(morpholin-4-yl)benzo(h)chromen-4-one |
| NU 7026 |
This section contains frequently‑asked‑questions about this compound, including basic parameters, properties, storage conditions and corresponding answers.
| Q: What are the storage conditions for 2-morpholin-4-ylbenzo[h]chromen-4-one? |
| A: Storage conditions for 2-morpholin-4-ylbenzo[h]chromen-4-one: 2-8°C. |
| Q: What is the polar surface area (PSA) of 2-morpholin-4-ylbenzo[h]chromen-4-one? |
| A: Polar surface area (PSA) of 2-morpholin-4-ylbenzo[h]chromen-4-one is 42.68000. |
| Q: What is the physical appearance of 2-morpholin-4-ylbenzo[h]chromen-4-one? |
| A: 2-morpholin-4-ylbenzo[h]chromen-4-one appears as solid | tan. |
| Q: What is the LogP of 2-morpholin-4-ylbenzo[h]chromen-4-one? |
| A: LogP of 2-morpholin-4-ylbenzo[h]chromen-4-one is 3.29. |
| Q: What is the SMILES notation of 2-morpholin-4-ylbenzo[h]chromen-4-one? |
| A: SMILES notation of 2-morpholin-4-ylbenzo[h]chromen-4-one is O=c1cc(N2CCOCC2)oc2c1ccc1ccccc12. |
| Q: What is the boiling point of 2-morpholin-4-ylbenzo[h]chromen-4-one? |
| A: Boiling point of 2-morpholin-4-ylbenzo[h]chromen-4-one is 459.9±45.0 °C at 760 mmHg. |
| Q: What is the molecular weight of 2-morpholin-4-ylbenzo[h]chromen-4-one? |
| A: Molecular weight of 2-morpholin-4-ylbenzo[h]chromen-4-one is 281.306. |
| Q: What is the CAS number of 2-morpholin-4-ylbenzo[h]chromen-4-one? |
| A: CAS number of 2-morpholin-4-ylbenzo[h]chromen-4-one is 154447-35-5. |
| Q: How is the water solubility of 2-morpholin-4-ylbenzo[h]chromen-4-one? |
| A: Water solubility of 2-morpholin-4-ylbenzo[h]chromen-4-one: DMSO: 3 mg/mL at 60 °C, soluble. |
| Q: What is the InChIKey of 2-morpholin-4-ylbenzo[h]chromen-4-one? |
| A: InChIKey of 2-morpholin-4-ylbenzo[h]chromen-4-one is KKTZALUTXUZPSN-UHFFFAOYSA-N. |
This table lists manufacturers and suppliers of this compound, including vendor names and product supply reference information.
| Shanghai Nianxing Industrial Co., Ltd |