GANT-61-NSC-136476-DataSheet-生命科學(xué)試劑-MedChemExpress

1、Hotline: 400-820-3792Inhibitors Agonists Screening Librarieswww.MedChemEGANT 61Cat. No.: HY-13901CAS No.: 500579-04-4Synonyms: NSC 136476分式: CHN分量: 429.6作靶點(diǎn): Gli; Autophagy作通路: Stem Cell/Wnt; Autophagy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) DMSO : 25 mg/mL (58

2、.19 mM; Need ultrasonic)H2O : 40% PEG300 5% Tween-80 45% salineSolubility: 2.5 mg/mL (5.82 mM); Clear solution2. 請(qǐng)依序添加每種溶劑： 10% DMSO 90% (20% SBE-CD in saline)Solubility: 2.5 mg/mL (5.82 mM); Suspended solution; Need ultrasonic1/3 Master of Small Molecules 您邊的抑制劑師www.MedChemE3. 請(qǐng)依序添加每種溶劑： 10% DMSO 9

3、0% corn oilSolubility: 2.5 mg/mL (5.82 mM); Clear solutionBIOLOGICAL ACTIVITY物活性 GANT 61是靶向Hedgehog/GLi通路的 Gli1 和 Gli2 抑制劑。IC50 & Target Gli1/2 1體外研究 GANT61 (20 M) induces greater cell death than targeting Smo (cyclopamine). GANT61 (0, 5, 10, 20 M)inhibits clonogenic survival of human colon carcinom

4、a cell lines. GANT61 (20 M, 0-72 hr) down-regulatesGli1 and Gli2 expression in HT29 cells. GANT61 (0, 10 M or 20 M) differentially regulates genes involvedin the balance between cell death and cell survival 1. GANT-61 inhibits cell viability and induces apoptosisin pancreatic CSCs. GANT-61 inhibits

5、expression of downstream targets of Shh pathway, decreases Gli-DNAinteraction, Gli transcriptional activity and Gli nuclear translocation in pancreatic CSCs. GANT-61differentially regulates genes involved in cell survival, cell death and pluripotency. GANT-61 inhibits motility,invasion and migration

6、 of CSCs 2. GANT61 sensitivity positively correlates to GLI1 and negatively to MYCNexpression in the neuroblastoma cell lines tested. GANT61 downregulates GLI1, c-MYC, MYCN and CyclinD1 expression and induces apoptosis of neuroblastoma cells 3.體內(nèi)研究 GANT-61 (40 mg/kg, i.p., three days per week) inhib

7、its CSC tumor growth in NOD/SCID IL2R null mice 2.GANT61 (50 mg/kg, p.o.) enhances the effects of chemotherapeutic drugs used in the treatment ofneuroblastoma in an additive or synergistic manner and reduces the growth of established neuroblastomaxenografts in nude mice 3.PROTOCOLCell Assay 2 Cells

8、(1.5104) are incubated with 0, 1, 5 and 10 M of GANT-61 in 250 L of culture medium in 96-wellplate for 48 and 72 h. Cell viability is determined by the XTT assay. In brief, a freshly prepared XTT-PMSlabeling mixture (50 L) is added to the cell culture. The absorbance is measured at 450 nm with corre

9、ctionat 650 nm. The cell viability is expressed as OD (OD450 OD650). The apoptosis is determined by FACSanalysis of propidium iodide (PI)-stained cells. In brief, cells are trypsinized, washed with PBS andresuspended in 200 L PBS with 10 L RNAase (10 mg/mL) and incubated at 37C for 30 min. Afterincu

10、bation, 50 L PI solution is added and cells are analyzed for apoptosis using a flow cytometry.MCE has not independently confirmed the accuracy of these methods. They are for reference only.Animal Humanized NOD/SCID/IL2Rgammanull mice are used for the assay. Before CSCs injection, mice areAdministrat

11、ion 2 humanized with tail vein injection of human normal CD34+ peripheral blood stem/progenitor cells.CD34+peripheral blood stem/progenitor cells (500 cells/mouse, 50-75 L volume) are injected through tailvein. After 3 days, human pancreatic CSCs (1103 cells mixed with Matrigel, Becton Dickinson, Be

12、dford, MA,in 75 L total volume, 50:50 ratio) are injected subcutaneously into the flanks of NOD/SCID IL2Rnull mice(46 weeks old). After two weeks of CSC implantation, mice (10 mice per group) are treated with GANT-61(02/3 Master of Small Molecules 您邊的抑制劑師www.MedChemEand 40 mg/kg body weight) ip thre

13、e times per week for 6 weeks. At the end of the experiment, mice areeuthanized, and tumors are isolated for biochemical analysis.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) Blood. 2016 Dec 8;128(23):2642-2654. Nat Commun. 2017 Jun 12;8:1

14、5773 ACS Appl Mater Interfaces. 2017 Dec 13;9(49):42544-42555. Cancer Lett. 2018 Apr 28;420:195-207. Cancer Lett. 2017 Jan 28;385:128-136.See more customer validations on HYPERLINK / www.MedChemEREFERENCES1. Mazumdar T, et al. Hedgehog signaling drives cellular survival in human colon carcinoma cell

15、s. Cancer Res. 2011 Feb 1;71(3):1092-102.2. Fu J, et al. GANT-61 inhibits pancreatic cancer stem cell growth in vitro and in NOD/SCID/IL2R gamma null mice xenograft. Cancer Lett.2013 Mar 1;330(1):22-32.3. Wickstrom M, et al. Targeting the hedgehog signal transduction pathway at the level of GLI inhibits neuroblastoma cell growth in vitroand in vivo. Int J Cancer