氯硝柳胺作用機(jī)制 - Medchemexpress - MCE中國

1、Product Data SheetNiclosamideCat. No.: HY-B0497CAS No.: 50-65-7分式: CHClNO分量: 327.12作靶點(diǎn): STAT; Parasite作通路: JAK/STAT Signaling; Stem Cell/Wnt; Anti-infection儲存式: 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) DMF : 5 mg/mL (15.28 mM; Need ultrasonic)DMSO : 4.55 mg/mL (13.9

2、1 mM; Need ultrasonic)H2O : 0.1 mg/mL (insoluble)SolventMass1 mg 5 mg 10 mgConcentration制備儲備液1 mM 3.0570 mL 15.2849 mL 30.5698 mL5 mM 0.6114 mL 3.0570 mL 6.1140 mL10 mM 0.3057 mL 1.5285 mL 3.0570 mL請根據(jù)產(chǎn)品在不同溶劑中的溶解度選擇合適的溶劑配制儲備液；旦配成溶液，請分裝保存，避免反復(fù)凍融造成的產(chǎn)品失效。儲備液的保存式和期限：-80C, 6 months; -20C, 1 month。-80C 儲存

3、時，請?jiān)?6 個內(nèi)使，-20C 儲存時，請?jiān)?1 個內(nèi)使。體內(nèi)實(shí)驗(yàn) 請根據(jù)您的實(shí)驗(yàn)動物和給藥式選擇適當(dāng)?shù)娜芙獍?。以下溶解案都請先按?In Vitro 式配制澄清的儲備液，再依次添加助溶劑：為保證實(shí)驗(yàn)結(jié)果的可靠性，澄 的儲備液可以根據(jù)儲存條件，適當(dāng)保存；體內(nèi)實(shí)驗(yàn)的作液，建議您現(xiàn)現(xiàn)配，當(dāng)天 使； 以下溶劑前顯的百分 指該溶劑在您配制終溶液中的體積占；如在配制過程中出現(xiàn)沉淀、析出現(xiàn)象，可 以通過加熱和/或超聲的式助溶1. 請依序添加每種溶劑： 10% DMF 40% PEG300 5% Tween-80 45% salineSolubility: 0.5 mg/mL (1.53 mM); Susp

4、ended solution; Need ultrasonicBIOLOGICAL ACTIVITY物活性Niclosamide (BAY2353) 種服物可利的氯化楊酰苯胺，具有驅(qū)和潛在的抗腫瘤活性。 NiclosamidePage 1 of 2 www.MedChemE(BAY2353) 可抑制STAT3，在 HeLa 細(xì)胞中IC50 0.25 M，并在細(xì)胞試驗(yàn)中抑制 DNA 復(fù)制。IC & Target STAT30.25 M (IC50, in HeLa cells)體外研究 Niclosamide is an inhibitor of STAT3, inhibiting STAT3-

5、mediated luciferase reporter activity with an IC50 of 0.25 M inHeLa cells. Niclosamide (1 M) inhibits the EGF-induced nuclear translocation of STAT3 in Du145 cells. Niclosamide (2 M) dose dependently inhibits the transcription of STAT3 downstream genes in Du145 cells. Niclosamide ( 10 M)induces G0/G

6、1 arrest and apoptosis of Du145 cancer cells in a dose dependent manner1. Niclosamide can blockSARS-CoV replication at a micromolar concentration in Vero E6 cells infected with SARS-CoV2. Niclosamide ( 7.5 M) promotes Frizzled1 endocytosis, downregulates Dishevelled-2 protein, and inhibits Wnt3A-sti

7、mulated beta-catenin stabilization and LEF/TCF reporter activity in U2OS cells3. Niclosamide inhibits the TNF-induced NF-Breporter activity in a dose- and time-dependent manner in U2OS cells. Niclosamide (125 nM) inhibits NF-B activationinduced by p65, IKK, IKK, IKK, and TAK1 in U2OS cells. Niclosam

8、ide ( 500 nM) completely block the time- anddose-dependent TNF-induced alteration of the NF-B-DNA complex in HL-60 cells. Niclosamide ( 10 nM) inhibitsconstitutive NF-B activation in U266 cells. Niclosamide inhibits TNF-induced degradation of IB and relocation ofp65 in a dose- and time-dependent man

9、ner in HL-60, Molm13, or AML primary cells. Niclosamide (500 nM) causesdecrease in TNF-induced NF-B-dependent gene products involved in cell survival in HL-60 cells. Niclosamide alsoinhibits the growth and induces robust apoptosis of AML cells associated with decreased Mcl-1 and XIAP levels andincre

10、ased intracellular ROS levels4.體內(nèi)研究 Niclosamide (40 mg/kg/d, i.p.) suppresses the growth of xenografted AML cells in nude mice bearing HL-60 xenografttumors4.PROTOCOLKinase Assay 1 All of the protein kinases are expressed either in Sf9 insect cells or in E.coli as recombinant GST-fusion proteins orH

11、is-tagged proteins. A radiometric protein kinase assay is used for measuring the kinase activity of the 22 proteinkinases. Briefly, for each protein kinase, 50 L reaction cocktail containing 60 mM HEPES-NaOH, 3 mM MgCl2, 3 mMMnCl2, 3 M Na-orthovanadate, 1.2 mM DTT, 50 g/mL PEG20000, 1 M -33P-ATP, Ni

12、closamide, adequate amountof enzyme and its substrate. The PKC-alpha assay additionally contain 1 mM Ca2, 4 mM EDTA, 5 g/mLphosphatidylserine and 1 g/mL 1, 2-Dioleyl-glycerol. The reaction cocktails are incubated at 37C for 60 minutesand stop with 50 L 2% (v/v) H3PO4. Incorporation of 33Pi is determ

13、ined with a microplate scintillation counter. Theactivities and the IC50 values are calculated using Quattro Workflow V2.28.MCE has not independently confirmed the accuracy of these methods. They are for reference only.Cell Assay 1 Cells are plated in 96-well culture plates with cell density of 3-4

14、103 cells/well and treat with Niclosamide by adding100 L medium containing Niclosamide of various concentrations on the second day. After 72-hours treatment, MTTis added to each well and incubated for additional 4-5 hours, and the absorbance is measured on a microplate readerat 570 nm. Cell growth i

15、nhibition is evaluated as the ratio of the absorbance of the sample to that of the control. Theresults are representative of at least 3 independent experiments.MCE has not independently confirmed the accuracy of these methods. They are for reference only.Animal Male nu/nu BALB/c mice are used in the

16、 assay. HL-60 cells are inoculated s.c. on the flanks of 4- to 6-wk-old mice.Administration 4 Tumors are measured every other day with use of calipers. Mice bearing HL-60 xenografts are randomized to receivetreatment with normal saline (control) or p-niclosamide for 15 days (n=7 animals each). Tumor

17、 volumes arecalculated by the following formula: a2b0.4, where a is the smallest diameter and b is the diameter perpendicularto a. After mice are euthanized, xenografts are dissected, weighed, or preserved.MCE has not independently confirmed the accuracy of these methods. They are for reference only

18、.Page 2 of 3 www.MedChemE戶使本產(chǎn)品發(fā)表的科研獻(xiàn) Cell Syst. 2018 Apr 25;6(4):424-443.e7. Biochem Pharmacol. 2019 Aug 26. pii: S0006-2952(19)30300-4. Patent. US20180263995A1.See more customer validations on HYPERLINK www.MedChemE www.MedChemEREFERENCES1. Ren, X., et al., Identification of niclosamide as a new small-molecule inhibitor of the STAT3 signaling pathway. ACS Medicinal Chemistry Letters, 2010.1(9): p. 454-459.2. Wu CJ, et al. Inhibition of severe acute respiratory syndrome coronavirus replication by niclosamide. Antim