Gambogic-Acid-Beta-Guttiferrin-DataSheet-生命科学试剂-MedChemExpress

1、Hotline: 400-820-3792Inhibitors Agonists Screening Librarieswww.MedChemEGambogic AcidCat. No.: HY-N0087CAS No.: 2752-65-0Synonyms: Beta-Guttiferrin分式: CHO分量: 628.75作靶点: Bcl-2 Family; Autophagy作通路: Apoptosis; Autophagy储存式: Powder -20C 3 years4C 2 yearsIn solvent -80C 6 months-20C 1 month溶解性数据体外实验 DMS

2、O : 100 mg/mL (159.05 mM)H2O : 40% PEG300 5% Tween-80 45% salineSolubility: 2.5 mg/mL (3.98 mM); Clear solution2. 请依序添加每种溶剂： 10% DMSO 90% corn oil1/3 Master of Small Molecules 您边的抑制剂师www.MedChemESolubility: 2.5 mg/mL (3.98 mM); Clear solutionBIOLOGICAL ACTIVITY物活性 Gambogic Acid (Beta-Guttiferrin) 来

3、Garcinia hanburyi 树的藤黄树脂。Gambogic Acid (Beta-Guttiferrin)抑制 Bcl-XL，Bcl-2，Bcl-W，Bcl-B，Bfl-1 和 Mcl-1，IC50 分别为 1.47 M，1.21 M，2.02 M，0.66 M，1.06 M 和 0.79 M。IC50 & Target Bcl-B Mcl-1 Bfl-1 Bcl-20.66 M (IC50) 0.79 M (IC50) 1.06 M (IC50) 1.21 M (IC50)Bcl-xL Bcl-W Autophagy1.47 M (IC50) 2.02 M (IC50)体外研究 Ga

4、mbogic Acid (Beta-Guttiferrin) is a medicinal compound derived from the gamboges resin of the tree,Garcinia hanburyi. Gambogic Acid has documented cytotoxic activity against tumor cell lines in culture, withconcentrations required for killing 50% of cells (LD50 of 1 M). The activity of Gambogic Acid

5、 against the 6human anti-apoptotic Bcl-2-family proteins is contrasted, using FPAs. Gambogic Acid displaces to variousextents FITC-BH3 peptide binding to all 6 proteins, with apparent IC50 1.47 M for Bcl-XL, 1.21 M for Bcl-2,2.02 M for Bcl-W, 0.66 M for Bcl-B, 1.06 M for Bfl-1, and 0.79 M for Mcl-1

6、1. The growth inhibitoryeffects of Gambogic Acid or Cisplatin (CDDP) on A549, NCI-H460, and NCI-H1299 cells are assessed by theMTT assay after 48h exposure. A concentration-dependent inhibition of cell growth is observed withGambogic Acid and CDDP, with IC50s of 3.560.36 and 21.883.21M for A549 cell

7、s, 4.050.51 and25.764.03M for NCI-H460 cells, and 1.120.31M and 25.214.38M for NCI-H1299 cells 2.体内研究 To further investigate whether Gambogic Acid (Beta-Guttiferrin) synergises CDDP against tumour growth invivo, A549 tumors are implanted in SCID mice. When mice are treated with CDDP combined with Ga

8、mbogicAcid, the tumor inhibition rate is 69.3%, whereas those of mice treated with CDDP and GA alone are 57.2%and 29.0%, respectively 2.PROTOCOLCell Assay 2 The in vitro cell viability effects of Gambogic Acid, CDDP alone, or combined treatments are determined byMTT assay. The cells (2104 cells per

9、mL) are seeded into 96-well culture plates. After overnight incubation,A549 cells are treated with Gambogic Acid (0.44, 0.88, 1.75, 3.5, 7, 10.5 and 14 M); NCI-H460 cells aretreated with Gambogic Acid (0.5, 1, 2, 4, 8, 12 and 16 M); NCI-H1299 cells are treated with Gambogic Acid(0.125, 0.25, 0.5, 1,

10、 2 and 4 M). For the combined treatment in NSCLC cells, three sequences are tested:(a) Gambogic Acid followed by CDDP cells are exposed to Gambogic Acid for 48h, and then after washout ofGambogic Acid, cells are treated with CDDP for an additional 48h; (b) CDDP followed by Gambogic Acidcells are exp

11、osed to CDDP for 48h, and then after washout of CDDP, cells are treated with Gambogic Acidfor an additional 48h; and (c) concurrent treatment cells are exposed to both Gambogic Acid and ADM for 48h. The nature of the drug interaction is analysed by using the combination index (CI) 2.2/3 Master of Sm

12、all Molecules 您边的抑制剂师www.MedChemEMCE has not independently confirmed the accuracy of these methods. They are for reference only.Animal Mice 2Administration 2 To determine the in vivo antitumour activity of Gambogic Acid combined with CDDP, viable A549 cells(5106/100L PBS per mouse) are subcutaneousl

13、y injected into the right flank of 7- to 8-week-old maleSCID mice. When the average tumor volume reach 100mm3, the mice are randomly divided into fourtreatment groups, including control (saline only, n=5), Gambogic Acid (3.0mg/kg per 2 days, intravenously;n=6), CDDP (4mg/kg per week, intravenously;

14、n=6), and sequential combination (CDDP treatment one daybefore Gambogic Acid treatment, n=6). CDDP (4mg/kg, weekly) is generally administered at doses less thanthe maximum-tolerated dose in an attempt to allow any additive effects of combination treatment withplatinum-based agents and Gambogic Acid

15、to be more easily detected. Tumor size is measured once every2 days with a calipre. Body weight is recorded once every 2 days. After 14 days, the mice are killed and thetumors are excised and stored at -80C until further analysis.MCE has not independently confirmed the accuracy of these methods. The

16、y are for reference only.REFERENCES1. Zhai D, et al. Gambogic acid is an antagonist of antiapoptotic Bcl-2 family proteins. Mol Cancer Ther. 2008 Jun;7(6):1639-46.2. Wang LH, et al. Gambogic acid synergistically potentiates cisplatin-induced apoptosis in non-small-cell lung cancer through suppressingNF-B and MAPK/HO-1 signallin