IWP-2 - Wnt 抑制劑 - 生命科學(xué)試劑 - MedChemExpress

1、Hotline: 400-820-3792Inhibitors Agonists Screening Librarieswww.MedChemEIWP-2Cat. No.: HY-13912CAS No.: 686770-61-6分式: CHNOS分量: 466.6作靶點: Wnt作通路: Stem Cell/Wnt儲存式: Powder -20C 3 years4C 2 yearsIn solvent -80C 6 months-20C 1 month溶解性數(shù)據(jù)體外實驗 DMSO : 2 mg/mL (4.29 mM; Need ultrasonic)H2O : 0.1 mg/mL (ins

2、oluble)Mass Solvent1 mg 5 mg 10 mg Concentration制備儲備液1 mM 2.1432 mL 10.7158 mL 21.4316 mL5 mM - - -10 mM - - -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，并請注意儲備液的保存式和期限。BIOLOGICAL ACTIVITY物活性 IWP-2 抑制 Wnt 加和分泌，IC50 為 27 nM。IC50 & Target IC50: 27 nM (Wnt) 1體外研究IWP-2, an inhibitor of WNT processing and secretion. IW

3、P-2 significantly enhances the anti-proliferativeeffect of LEF. It is also obvious that the combination of LEF and IWP-2 could minimize the expression of -1/3 Master of Small Molecules 您邊的抑制劑師www.MedChemEcatenin, c-Myc, Cyclin D1, Bcl2 and Bax to the largest extent compared with single agents 2. Fol

4、lowingtreatment in the MKN28 cell line for four days, 10-50 M IWP-2 significantly suppressed the proliferation ofMKN28 cells (P 3.體內(nèi)研究 To evaluate the efficacy of IWP-2 in vivo, 200 L each of IWP-2-liposome or free liposome i separatelyinjected into C57BL/6 mice intraperitoneally about 2 h before in

5、jection of a similar volume of either blue-dye-filled latex beads or E. coli DH5. IWP-2 causes significant reduction in the uptake of blue beads as well asE. coli as assessed by CFUs in peritoneal lavage cells within 2 h. In addition, the levels of TNF- and IL-6 inthe lavage fluid of the correspondi

6、ng mice are reduced by 2-4-fold compared with control values.Interestingly, IWP-2 even induces a considerable increase in secretion of the anti-inflammatory cytokine IL-10 4. Pretreatment with IWP-2 significantly (P 5.PROTOCOLCell Assay 2 The human RCC cell lines 786O and Caki-2 (5103) are seeded in

7、to 96-well plates. Cell viability is estimatedby MST assay after Caki-2 acells are incubated with ncreasing concentrations of LEF together with 20 MIWP-2 for 48 h.After treatment, 10 L MTS is added into each well for 2 h incubation. The absorbance ismeasured using a model ELX800 Micro Plate Reader a

8、t 490 nm. For colony formation assay, Caki-2 cellsare trypsinized to single cell suspensions and seeded into fresh 6-well plates at 1000 cells/well. Then cellsare incubated with LEF at depicted concentrations for 7 days. Colonies are fixed with absolute methanol for15 min and then stained with 0.1%

9、crystal violet for 20 min. After washing with PBS three times, the colonieswith a diameter over 2 mm are visualized by a digital camera 2.MCE has not independently confirmed the accuracy of these methods. They are for reference only.Animal Mice 4Administration 45 About 3-mo-old C57BL/6 mice are hous

10、ed four to five in a cage at 23C in a 12-h light/dark cycle. Mice areinjected intraperitoneally (i.p.) first with either 200 L of liposome-IWP2 (LI) or liposome (L) and then after 2 hwith 1108 or 2108 CFU E. coli in 200 L of sterile PBS. After 2 h or 24 h mice are killed, and the peritonealcavity is

11、 washed with 5 mL of sterile ice-cold PBS. The peritoneal lavage fluid is centrifuged at 300 g for 5min, the cell pellet is resuspended in RPMI 1640 complete medium, and the supernatant is used for cytokineassay. For ex vivo experiments, peritoneal phagocytes are isolated as above from normal mice,

12、and equalnumbers of cells are plated in medium overnight at 37C in 5% CO2 before performing further experiments.Rats 5Adult, male, and healthy Wistar rats weighing 220-280 g are used. Rats are randomly divided into 6 groupsas follows (n=72, 12 per group): (1) Sham group (Group S), (2) I/R group (Gro

13、up I/R), (3) I/R+DMSO group(Group DMSO), (4) I/R+IWP group (Group IWP), (5) SP group (Group SP), and (6) SP+Wnt inhibitor IWP-2group (Group SP+IWP). The hearts are continuously perfused for 120 min in Group S. After 10 min ofequilibration, the isolated hearts are continuously perfused for 20 min, th

14、en subjected to 30 min of ischemiafollowed by 60 min of reperfusion in Group I/R; Groups DMSO, IWP, SP and SP+IWP receive 15 min ofperfusion with K-H solution containing 0.5 mL/L DMSO, 10 M IWP (SIGMA-ALDRICH, USA), 2.4 vol%Sevoflurane, 2.4 vol% Sevoflurane+10 M IWP, respectively, followed by 5 min

15、washout before I/R.MCE has not independently confirmed the accuracy of these methods. They are for reference only.2/3 Master of Small Molecules 您邊的抑制劑師www.MedChemE戶使本產(chǎn)品發(fā)表的科研獻 Patent. US20180263995A1.See more customer validations on HYPERLINK / www.MedChemEREFERENCES1. Chen B, et al. Small molecule-m

16、ediated disruption of Wnt-dependent signaling in tissue regeneration and cancer. Nat Chem Biol. 2009Feb;5(2):100-7.2. Chen Y, et al. Inhibition of canonical WNT/-catenin signaling is involved in leflunomide (LEF)-mediated cytotoxic effects on renalcarcinoma cells. Oncotarget. 2016 Jul 6.3. Mo ML, et

17、 al. Inhibition of the Wnt palmitoyltransferase porcupine suppresses cell growth and downregulates the Wnt/-catenin pathwayin gastric cancer. Oncol Lett. 2013 May;5(5):1719-1723.4. Maiti G, et al. The Wingless homolog Wnt5a stimulates phagocytosis but not bacterial killing. Proc Natl Acad Sci U S A. 2012 Oct9;109(41):16600-5.5. Liu JD, et al. Wnt/Glycogen Synthase Kinase 3/-catenin Signaling Activation Mediated Sevoflurane Preconditioning-induced