NU7026

製品コードS2893 バッチS289301

化学情報

	Synonyms	LY293646	Storage (From the date of receipt)	3 years -20°C powder 1 years -80°C in solvent
	化学式	C₁₇H₁₅NO₃
	分子量	281.31	CAS No.	154447-35-5
Solubility (25°C)*	体外	DMSO	1 mg/mL (3.55 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.

溶剤液（一定の濃度）を調合する

生物活性

製品説明	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.
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]
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]

製品説明

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.

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]

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]

プロトコル(参考用のみ)

キナーゼアッセイ	Recombinant kinase assay
キナーゼアッセイ	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.
細胞アッセイ	細胞株	A549 cells
	濃度	10 μM
	反応時間	3 h
	実験の流れ	Cells were treated with indicated concentration of drug for 3 h.
動物実験	動物モデル	Female BALB/c mice
	投薬量	25 mg/kg
	投与方法	intraperitoneal injection or orally

参考

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カスタマーフィードバック

: 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]

Selleckの高級品が、幾つかの出版された研究調査結果（以下を含む）で使われた：

LC3B drives transcription-associated homologous recombination via direct interaction with R-loops [ Nucleic Acids Res, 2024, gkae156]	PubMed: 38412240
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
DNA Polymerase η promotes non-homologous end joining upon etoposide exposure dependent on the scaffolding protein Kap1 [ J Biol Chem, 2022, S0021-9258(22)00301-5]	PubMed: 35339488
The VRK1 chromatin kinase regulates the acetyltransferase activity of Tip60/KAT5 by sequential phosphorylations in response to DNA damage [ Biochim Biophys Acta Gene Regul Mech, 2022, 1865(8):194887]	PubMed: 36280132
Plasticity of extrachromosomal and intrachromosomal BRAF amplifications in overcoming targeted therapy dosage challenges [ Cancer Discov, 2021, candisc.0936.2020]	PubMed: 34930786

長期の保管のために-20°Cの下で製品を保ってください。

人間や獣医の診断であるか治療的な使用のためにでない。

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