NU7441 (KU-57788)

製品コードS2638 バッチS263804

化学情報

	Synonyms	N/A	Storage (From the date of receipt)	3 years -20°C powder 1 years -80°C in solvent
	化学式	C₂₅H₁₉NO₃S
	分子量	413.49	CAS No.	503468-95-9
Solubility (25°C)*	体外	DMSO	3 mg/mL warmed with 50ºC water bath (7.25 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	NU7441 (KU-57788) is a highly potent and selective DNA-PK inhibitor with IC50 of 14 nM and also inhibits mTOR and PI3K with IC50 of 1.7 μM and 5 μM in cell-free assays, respectively. It reduces the frequency of NHEJ while increasing the rate of HDR following Cas9-mediated DNA cleavage.
in vitro	NU7441 increases the persistence of γH2AX foci after ionizing radiation–induced or etoposide-induced DNA damage. NU7441 (0.5 μM or 1 μM) appreciably increases G2-M accumulation induced by ionizing radiation, etoposide, and doxorubicin in both SW620 and LoVo cells. ^[2] NU7441 causes persistence of doxorubicin- and ionising radiation-induced DNA double-strand break and also slightly decreases homologous recombination activity DNA-PK-proficient M059-Fus-1 and DNA-PK-deficient M059 J human tumour cells. ^[3] NU7441 inhibits UV-induced RPA p34 hyperphosphorylation in a dose-dependent manner both in cells lacking and cells expressing polymerase η. ^[4] NU7441 increases levels of fludarabine-induced γH2AX foci and correspondingly decreased fludarabine-induced cell death in chronic lymphocytic leukemia cells. ^[5] NU7441 also inhibits mitoxantrone-induced DNA-PKcs autophosphorylation and repair in chronic lymphocytic leukemia cells. ^[6] It reduces the frequency of NHEJ while increasing the rate of HDR following Cas9-mediated DNA cleavage^[7].
in vivo	NU7441 intraperitoneally administrated at dose of 10 mg/kg maintains for at least 4 hours shows nontoxic and increases etoposide-induced tumor growth delay 2-fold in mice bearing SW620 xenografts. ^[2]

プロトコル(参考用のみ)

細胞アッセイ	細胞株	SW620, LoVo, V3-YAC and V3 cells
	濃度	0.5 μM or 1 μM
	反応時間	17 hours
	実験の流れ	The effect of NU7441 on cellular survival following exposure to etoposide, doxorubicin, and ionizing radiation is measured in SW620, LoVo, V3, and V3-YAC cells by clonogenic assays. Briefly, growing cells in six-well plates or 6-cm dishes are exposed to etoposide or doxorubicin with or without NU7441 (0.5 or 1.0 μM) for 16 hours. For radiosensitization studies, NU7441 is added to the cells 1 hour before irradiation. V3 and V3-YAC cells are exposed to γ-irradiation (3.1 Gy/min ¹³⁷Cesium). SW620 and LoVo are exposed to X-irradiation (2.9 Gy/min at 230 kV, 10 mA) due to the equipment available. After irradiation, the cells are incubated with or without NU7441 for a further 16 hours. Cells are then harvested by trypsinization, counted, and seeded into 10-cm diameter Petri dishes at densities varying from 100 to 10⁵ per dish in drug-free medium for colony formation. Colonies are stained with crystal violet after 10 to 14 days and counted with an automated colony counter. The survival reduction factor (SRF) is calculated as the surviving fraction of cells in the absence of NU7441 divided by the surviving fraction of cells in the presence of NU7441 for any given dose or concentration of cytotoxic agent. The dose modification ratio (DMR90) is calculated as the concentration/dose of cytotoxic agent required to kill 90% of the cells in the absence of NU7441 divided by the concentration/dose of cytotoxic agent required to kill 90% of the cells in the presence of NU7441.
動物実験	動物モデル	Female rude mice bearing SW620 xenografts
	投薬量	10 mg/kg
	投与方法	Intraperitoneally administrated

参考

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カスタマーフィードバック

: Data from [Data independently produced by Toxicol Sci, 2014, 10.1093/toxsci/kfu207]

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

: Data from [Nucleic Acids Res, 2013, 41, 10157-69]

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：

Comprehensive multi-omics analysis reveals WEE1 as a synergistic lethal target with hyperthermia through CDK1 super-activation [ Nat Commun, 2024, 15(1):2089]	PubMed: 38453961
Kaposi's sarcoma herpesvirus exploits the DNA damage response to circularize its genome [ Nucleic Acids Res, 2024, gkad1224]	PubMed: 38180827
The DNA-dependent protein kinase catalytic subunit exacerbates endotoxemia-induced myocardial microvascular injury by disrupting the MOTS-c/JNK pathway and inducing profilin-mediated lamellipodia degradation [ Theranostics, 2024, 14(4):1561-1582]	PubMed: 38389837
DNA damage remodels the MITF interactome to increase melanoma genomic instability [ Genes Dev, 2024, 38(1-2):70-94]	PubMed: 38316520
SMARCAL1 ubiquitylation controls its association with RPA-coated ssDNA and promotes replication fork stability [ PLoS Biol, 2024, 22(3):e3002552]	PubMed: 38502677
Transcriptomic Data of Bt549 Triple Negative Breast Cancer Cells Treated with 20 Μm Nu7441, A Dna-Dependent Kinase Inhibitor [ SSRN, 2024, 12 Pages]	PubMed: none
Chromatin compartmentalization regulates the response to DNA damage [ Nature, 2023, 623(7985):183-192]	PubMed: 37853125
Reprogramming of palmitic acid induced by dephosphorylation of ACOX1 promotes β-catenin palmitoylation to drive colorectal cancer progression [ Cell Discov, 2023, 9(1):26]	PubMed: 36878899
Multiscale reorganization of the genome following DNA damage facilitates chromosome translocations via nuclear actin polymerization [ Nat Struct Mol Biol, 2023, 30(1):99-106]	PubMed: 36564591
ATM signaling modulates cohesin behavior in meiotic prophase and proliferating cells [ Nat Struct Mol Biol, 2023, 10.1038/s41594-023-00929-5]	PubMed: 36879153

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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