| CAS |
No.500579-04-4 |
| 英文名称 |
GANT 61 |
| 别名 |
NSC 136476 |
| 分子式 |
C27H35N5 |
| 分子量 |
429.6 |
| 溶解性 |
Soluble in Ethanol |
| 纯度 |
≥98% |
| 外观(性状) |
White to yellow Solid |
| 储存条件 |
Powder:2-8℃，2 years;Insolvent(母液):-20℃，6 months;-80℃，1 year |
| MDL |
MFCD14635408 |
| SMILES |
CN(C)C1=CC=CC=C1CN2C(C3=CC=NC=C3)N(CC4=CC=CC=C4N(C)C)CCC2 |
| InChIKey |
KVQOGDQTWWCZFX-UHFFFAOYSA-N |
| InChI |
InChI=1S/C27H35N5/c1-29(2)25-12-7-5-10-23(25)20-31-18-9-19-32(27(31)22-14-16-28-17-15-22)21-24-11-6-8-13-26(24)30(3)4/h5-8,10-17,27H,9,18-21H2,1-4H3 |
| PubChem CID |
421610 |
| 靶点 |
Gli |
| 通路 |
Hedgehog;Stem Cells |
| 背景说明 |
GANT 61是靶向Hedgehog/GLi通路的 Gli1 和 Gli2 抑制剂。 |
| 生物活性 |
GANT 61 is an inhibitor of Gli1 and Gli2 targeting the Hedgehog/GLI pathway.[1-3] |
| In Vitro |
GANT61 (20 μM) 比靶向 Smo (环巴胺) 诱导更多的细胞死亡。GANT61 (0，5，10，20 μM) 抑制人结肠癌细胞系的克隆形成存活。GANT61 (20 μM，0-72 小时) 下调 HT29 细胞中的 Gli1 和 Gli2 表达。GANT61 (0、10 μM 或 20 μM) 差异调节参与细胞死亡和细胞存活之间平衡的基因[1]。GANT-61 抑制细胞活力并诱导胰腺 CSC 细胞凋亡。GANT-61 抑制 Shh 通路下游靶标的表达，降低胰腺 CSC 中的 Gli-DNA 相互作用、Gli 转录活性和 Gli 核转位。GANT-61 差异调节参与细胞存活、细胞死亡和多能性的基因。GANT-61 抑制 CSCs 的运动、侵袭和迁移[2]。在测试的神经母细胞瘤细胞系中，GANT61 敏感性与 GLI1 呈正相关，与 MYCN 表达呈负相关。GANT61 下调 GLI1、c-MYC、MYCN 和 Cyclin D1 的表达并诱导神经母细胞瘤细胞凋亡[3]。 |
| In Vivo |
GANT-61 (40 mg/kg，腹腔注射，每周三天) 抑制 NOD/SCID IL2Rγ 缺失小鼠的 CSC 肿瘤生长[2]。 GANT61 (50 mg/kg，口服) 以相加或协同的方式增强用于处理神经母细胞瘤的化疗药物的作用，并减少裸鼠体内已建立的神经母细胞瘤异种移植物的生长[3]。 |
| 细胞实验 |
Cells (1.5×104) are incubated with 0， 1， 5 and 10 μM of GANT-61 in 250 μL of culture medium in 96-well plate for 48 and 72 h. Cell viability is determined by the XTT assay. In brief， a freshly prepared XTT-PMS labeling mixture (50 μL) is added to the cell culture. The absorbance is measured at 450 nm with λ correction at 650 nm. The cell viability is expressed as ΔOD (OD450?? OD650). The apoptosis is determined by FACS analysis of propidium iodide (PI)-stained cells. In brief， cells are trypsinized， washed with PBS and resuspended in 200 μL PBS with 10 μL RNAase (10 mg/mL) and incubated at 37°C for 30 min. After incubation， 50 μL PI solution is added and cells are analyzed for apoptosis using a flow cytometry. |
| 动物实验 |
Humanized NOD/SCID/IL2Rgammanull?mice are used for the assay. Before CSC’s injection， mice are 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 μL volume) are injected through tail vein. After 3 days， human pancreatic CSCs (1×103?cells mixed with Matrigel， Becton Dickinson， Bedford， MA， in 75 μL total volume， 50:50 ratio) are injected subcutaneously into the flanks of NOD/SCID IL2Rγnull?mice (4–6 weeks old). After two weeks of CSC implantation， mice (10 mice per group) are treated with GANT-61(0 and 40 mg/kg body weight) ip three times per week for 6 weeks. At the end of the experiment， mice are euthanized， and tumors are isolated for biochemical analysis. |
| 数据来源文献 |
[1]. Mazumdar T， et al. Hedgehog signaling drives cellular survival in human colon carcinoma cells. 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 vitro and in vivo. Int J Cancer. 2013 Apr 1;132(7):1516-24. |
| 规格 |
1mg 5mg 10mg 50mg |
| 单位 |
瓶 |
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