KU-57788-NU7441-DataSheet-生命科學(xué)試劑-MedChemExpress

1、Hotline: 400-820-3792Inhibitors Agonists Screening Librarieswww.MedChemEKU-57788Cat. No.: HY-11006CAS No.: 503468-95-9Synonyms: NU7441分式: CHNOS分量: 413.49作靶點(diǎn): DNA-PK; CRISPR/Cas9作通路: Cell Cycle/DNA Damage; PI3K/Akt/mTOR儲(chǔ)存式: Powder -20C 3 years4C 2 yearsIn solvent -80C 6 months-20C 1 month溶解性數(shù)據(jù)體外實(shí)驗(yàn) DM

2、SO : 14.29 mg/mL (34.56 mM; Need ultrasonic)Mass Solvent1 mg 5 mg 10 mg Concentration制備儲(chǔ)備液1 mM 2.4184 mL 12.0922 mL 24.1844 mL5 mM 0.4837 mL 2.4184 mL 4.8369 mL10 mM 0.2418 mL 1.2092 mL 2.4184 mL請(qǐng)根據(jù)產(chǎn)品在不同溶劑中的溶解度，選擇合適的溶劑配制儲(chǔ)備液，并請(qǐng)注意儲(chǔ)備液的保存式和期限。體內(nèi)實(shí)驗(yàn)請(qǐng)根據(jù)您的實(shí)驗(yàn)動(dòng)物和給藥式選擇適當(dāng)?shù)娜芙獍?，配制前?qǐng)先配制澄清的儲(chǔ)備液，再依次添加助溶劑(為保證實(shí)驗(yàn)結(jié)果的可靠性，

3、體內(nèi)實(shí)驗(yàn)的作液，建議您現(xiàn)現(xiàn)配，當(dāng)天使；澄清的儲(chǔ)備液可以根據(jù)儲(chǔ)存條件，適當(dāng)保存；以下溶劑前的百分 指該溶劑在您配制終溶液中的體積占)：1. 請(qǐng)依序添加每種溶劑： 10% DMSO 40% PEG300 5% Tween-80 45% salineSolubility: 1.43 mg/mL (3.46 mM); Clear solution2. 請(qǐng)依序添加每種溶劑： 10% DMSO 90% (20% SBE-CD in saline)Solubility: 1.43 mg/mL (3.46 mM); Clear solution3. 請(qǐng)依序添加每種溶劑： 10% DMSO 90% corn o

4、il1/3 Master of Small Molecules 您邊的抑制劑師www.MedChemESolubility: 1.43 mg/mL (3.46 mM); Clear solutionBIOLOGICAL ACTIVITY物活性 KU-57788種有效的，選擇性的 DNA-PK 抑制劑，IC50 值為 13 nM。IC50 & Target DNA-PK CRISPR/Cas913 nM (IC50)體外研究 NU7441 at non-toxic concentration of 0.3 M induces radio-sensitization in non-small ce

5、ll lung cancer cellsirradiated with low-LET and high-LET radiation, and does not show double strand break-repair inhibition inirradiated cells. NU7441 (3 M) shows significantly increased persistent -H2AX signals. NU7441 (0.3 M)causes significant G2/M arrest and a remarkable increase of DNA fragmenta

6、tion and enhances cellularsenescence in irradiated H1299 cells 1. NU7441 (0.5 to 10 M) inhibits the growth of liver cancer HepG2cells dose- and time-dependently. NU7441 reduces pDNA-PKcs (S2056) protein expression in liver cancercells. Furthermore, double treatment of NU7441 and 60Co IR affects DNA

7、damage repair 2. NU7441 issolvent-exposed in BRD4, this inhibitor can be classified as a Type I BRD inhibitor 4. NU7441 reduces thefrequency of NHEJ while increasing the rate of HDR following Cas9-mediated DNA cleavage 5.體內(nèi)研究 lung cancer cells irradiated with low-LET and high-LET radiation, and does

8、 not show double strand break-repair inhibition in irradiated cells. KU-57788 (3 M) shows significantly increased persistent -H2AX signals.KU-57788 (0.3 M) causes significant G2/M arrest and a remarkable increase of DNA fragmentation andenhances cellular senescence in irradiated H1299 cells 1. KU-57

9、788 (0.5 to 10 M) inhibits the growth ofliver cancer HepG2 cells dose- and time-dependently. KU-57788 reduces pDNA-PKcs (S2056) proteinexpression in liver cancer cells. Furthermore, double treatment of KU-57788 and 60Co IR affects DNAdamage repair 2. KU-57788 weakly inhibits BRD4 and BRDT with IC50s

10、 of 1 M and 3.5 M, respectively.KU-57788 is solvent-exposed in BRD4, this inhibitor can be classified as a Type I BRD inhibitor 4. KU-57788 reduces the frequency of NHEJ while increasing the rate of HDR following Cas9-mediated DNAcleavage 5.PROTOCOLKinase Assay 4 The inhibitory activities of compoun

11、ds against BRD4-1 and BRDT-1 are assessed by DSF using aStepOnePlus Real-Time PCR system. Purified BRD4-1 (4 M final concentration; 10 mM HEPES (pH7.5),100 mM NaCl, and 1 mM DTT), and BRDT-1 (4 M final concentration; 50 mM phosphate (pH7.4), 100 mMNaCl, and 1 mM DTT) are assayed, in quadruplicates,

12、in a 96-well plate. Inhibitors are added to a finalconcentration of 100 M and 2% DMSO. Protein Thermal Shift Dye (1:8000) is used as the fluorescentprobe, and fluorescence is measured using the ROX Reporter channel (620 nm). Protein stability isinvestigated by programing the thermocycler to increase

13、 the temperature from 25 to 99C using 0.2Cincrements and 10 s incubations per increment. The inflection point of the transition curve/meltingtemperature (Tm) is calculated using the Boltzmann equation within the Protein Thermal Shift Software(v.1.1). JQ1(+) and dinaciclib are used as controls for st

14、rong and weak binders of BRD4-1, respectively. The2/3 Master of Small Molecules 您邊的抑制劑師www.MedChemETm is calculated by using DMSO control wells as a reference.MCE has not independently confirmed the accuracy of these methods. They are for reference only.Cell Assay 2 HepG2 cells (4000 per well) are c

15、ultured in a 96-well plate for 24 h. Once the cells complete the attachment,0.1 M, 1 M, 5 M, and 10 M of KU-57788 are added to the culture media. After 12 h of KU-57788treatment, 10% CCK-8 solution is added into the culture media, and the incubation continued for two h.OD450 values are determined by

16、 a spectrometer, and the results are analyzed to measure the cell growth.MCE has not independently confirmed the accuracy of these methods. They are for reference only.戶使本產(chǎn)品發(fā)表的科研獻(xiàn) J Mol Med (Berl). 2019 Jun 14. Neoplasia. 2018 Mar 28;20(5):478-488. Harvard Medical School LINCS LIBRARYSee more custom

17、er validations on HYPERLINK / www.MedChemEREFERENCES1. Sunada S, et al. Nontoxic concentration of DNA-PK inhibitor NU7441 radio-sensitizes lung tumor cells with little effect on double strandbreak repair. Cancer Sci. 2016 Sep;107(9):1250-52. Yang C, et al. NU7441 Enhances the Radiosensitivity of Liv

18、er Cancer Cells. Cell Physiol Biochem. 2016;38(5):1897-9053. Hardcastle IR, et al. Discovery of potent chromen-4-one inhibitors of the DNA-dependent protein kinase (DNA-PK) using a small-molecule library approach. J Med Chem. 2005 Dec 1;48(24):7829-464. Ember SW, et al. The acetyl-lysine binding site of bromodomain-containing protein 4 (BRD4) interacts with diverse kinase inhibitors.ACS Chem Biol. 2014 Feb 25.5. Robert F, et al. Pharmacological inhibition