GANT 58
(Synonyms: 4,44乔,4乔(2,3,4,5-Thiophentetrayl)tetrakis-pyridine,NSC 75503;GANT58;GANT-58;NSC-75503) 目录号 : GC16789
An inhibitor of Gli transcription
Cas No.:64048-12-0
Sample solution is provided at 25 µL, 10mM.
;)
,-1-7$$$37316672.jpg');)
;)
;)
$$$36806353.jpg');)
;33(7)%EF%BC%9A546-561$$$37156877.jpg');)
;)
;)
;)
%201124-1138.$$$35908550.jpg');)
%20766-780.$$$37100057.jpg');)
%20418-432.$$$36893736.jpg');)
%EF%BC%9A-240-255.$$$35108512.jpg');)
533-545$$$36543525.jpg');)
%201-13.$$$36600053.jpg');)
;)
Quality Control & SDS
- View current batch:
- Purity: >99.50%
- COA (Certificate Of Analysis)
- SDS (Safety Data Sheet)
- Datasheet
Cell experiment: | HEK293 cells are transfected with GLI1 expression plasmid, together with the reporter plasmids 12× GliBS-Luc and R-Luc on 10 cm plates (day 0). Twenty-four hours later, cells are seeded in white 96 well plates with clear bottom at a density of 15,000 cells per well. Cells are allowed to attach, and compounds are added at a final concentration of 10 μM in DMSO (0.5% final DMSO concentration) (day 1.5). Cells are grown for another 24 h, subsequently lysed, and then analyzed by using the Dual Luciferase kit. Plates are read on a Berthold Technologies microplate luminometer. Subconfluent cells are grown in reduced FBS (2.5%) for 48 h in the presence of 5 μM test compound (or DMSO) on white 96 well plates with clear bottom. Subsequently, cells are labeled for 2 h with BrdU, fixed, and analyzed. Samples are read on a Molecular Devices SpectraMax Gemini EM[1]. |
Animal experiment: | Mice[1] 5×106 22Rv1 cells are suspended in a total volume of 100 μL of a 1:1 mixture of RPMI medium 1640:Matrigel (E1270). The cell suspension is injected s.c. at the posterior flank of female BALB/c nude mice (nu/nu). Tumors are grown until they reached a median size of ≈250 mm3 (5-6 days). Animals are randomly divided into four groups (n=4-5) and treated with solvent only (corn oil:ethanol, 4:1) or compounds in solvent (50 mg/kg) for 16 days s.c. injections of compounds are performed several centimeters away from the tumor. Tumor volumes are calculated by the formula length×width×0.5×(length+width). At the end of the treatment period, animals are given a BrdU pulse (50 mg/kg) for 30 min, and tumors are removed. All animal experiments are approved by local ethics authorities. |
References: [1]. Lauth M, et al. Inhibition of GLI-mediated transcription and tumor cell growth by small-molecule antagonists. Proc Natl Acad Sci U S A. 2007 May 15;104(20):8455-60. | |
GANT 58 is an antagonist of GLI that inhibits GLI1-induced transcription with an IC50 value of 5 μM [1].
GLI1 is a human glioblastoma isolated protein which belongs to GLI protein family. GLI proteins act as effectors in Hedgehog signaling pathway and get involved in cell proliferation, determination and patterning during embryo development.
GANT 58 is considered to inhibit GLI1-mediated gene trans-activation with a high selectivity for Hedgehog signaling pathway. When TNF signaling/NFkB activation, glucocorticoid, receptor gene transactivation, and the Ras-Raf-Mek-Mapk cascade were treated with GANT 58, no inhibition was observed. When SAG-treated shh-L2 cells were treated with 10 μM GANT 58 for 48 hr, the reduction of Hedgehog pathway signaling was observed, whereas Gli1 mRNA level reduction was induced by the treatment of 10 μM GANT 58 for 2-3 days. Indeed, GANT 58 was confirmed as inhibitor of Hedgehog signaling pathway downstream Sufu and Smo [1]. Furthermore, GANT 58 treatments for 48 hr resulted in the significant reduction of cell viability in a dose-dependent manner for CCRFeCEM, CEM7e14, CEM1e15 and Jurkat cells. When CCRFeCEM cells were treated with 10 μM GANT 58 for 48 hr, the percentage of cells in G1/S phase increased whereas the percentage in G2/M phase decreased [2].
In mouse model with xenograft, daily s.c. injection of GANT 58 resulted in significant suppression of tumor cell growth. 50 mg/kg/d GANT 58 injections for 18 days induced the suppression of additional xenograft growth and restrict the increase of tumor size. No side effects were observed during the treatment [1].
References:
[1] Lauth M, Bergstr?m ?sa, Shimokawa T, Toftg?rd R. Inhibition of GLI-mediated transcription and tumor cell growth by small-molecule antagonists.?Proceedings of the National Academy of Sciences of the United States of America. 2007,104(20):8455-8460.
[2] Hou X, Chen X, Zhang P, et al. Inhibition of hedgehog signaling by GANT58 induces apoptosis and shows synergistic antitumor activity with AKT inhibitor in acute T cell leukemia cells. Biochimie. 2014, 101:50-9
| Cas No. | 64048-12-0 | SDF | |
| 别名 | 4,44乔,4乔(2,3,4,5-Thiophentetrayl)tetrakis-pyridine,NSC 75503;GANT58;GANT-58;NSC-75503 | ||
| 化学名 | 4-(2,4,5-tripyridin-4-ylthiophen-3-yl)pyridine | ||
| Canonical SMILES | C1=CN=CC=C1C2=C(SC(=C2C3=CC=NC=C3)C4=CC=NC=C4)C5=CC=NC=C5 | ||
| 分子式 | C24H16N4S | 分子量 | 392.48 |
| 溶解度 | ≥ 18.95 mg/mL in DMSO, ≥ 14.9 mg/mL in EtOH with ultrasonic and warming | 储存条件 | Store at -20°C |
| General tips | 请根据产品在不同溶剂中的溶解度选择合适的溶剂配制储备液；一旦配成溶液，请分装保存，避免反复冻融造成的产品失效。 储备液的保存方式和期限：-80°C 储存时，请在 6 个月内使用，-20°C 储存时，请在 1 个月内使用。 为了提高溶解度，请将管子加热至37℃，然后在超声波浴中震荡一段时间。 |
||
| Shipping Condition | 评估样品解决方案：配备蓝冰进行发货。所有其他可用尺寸：配备RT，或根据请求配备蓝冰。 | ||
| 制备储备液 | |||
 |
1 mg | 5 mg | 10 mg |
| 1 mM | 2.5479 mL | 12.7395 mL | 25.479 mL |
| 5 mM | 0.5096 mL | 2.5479 mL | 5.0958 mL |
| 10 mM | 0.2548 mL | 1.274 mL | 2.5479 mL |
| 第一步：请输入基本实验信息（考虑到实验过程中的损耗，建议多配一只动物的药量） | ||||||||||
| 给药剂量 | mg/kg |  |
动物平均体重 | g | |
每只动物给药体积 | ul | |
动物数量 | 只 |
| 第二步：请输入动物体内配方组成（配方适用于不溶于水的药物；不同批次药物配方比例不同，请联系GLPBIO为您提供正确的澄清溶液配方） | ||||||||||
| % DMSO % % Tween 80 % saline | ||||||||||
| 计算重置 | ||||||||||
计算结果:
工作液浓度： mg/ml；
DMSO母液配制方法： mg 药物溶于 μL DMSO溶液（母液浓度 mg/mL，
体内配方配制方法：取 μL DMSO母液，加入 μL PEG300，混匀澄清后加入μL Tween 80，混匀澄清后加入 μL saline，混匀澄清。
1. 首先保证母液是澄清的；
2.
一定要按照顺序依次将溶剂加入，进行下一步操作之前必须保证上一步操作得到的是澄清的溶液，可采用涡旋、超声或水浴加热等物理方法助溶。
3. 以上所有助溶剂都可在 GlpBio 网站选购。