| CAS |
No.64048-12-0 |
| 英文名称 |
GANT 58 |
| 别名 |
NSC 75503 |
| 分子式 |
C24H16N4S |
| 分子量 |
392.48 |
| 溶解性 |
Soluble in DMSO |
| 纯度 |
≥98% |
| 外观(性状) |
Light yellow to yellow Solid |
| 储存条件 |
Powder:2-8℃，2 years;Insolvent(母液):-20℃，6 months;-80℃，1 year |
| EC |
EINECS 200-258-5 |
| MDL |
MFCD01103196 |
| SMILES |
C1(C2=C(C(C3=CC=NC=C3)=C(S2)C4=CC=NC=C4)C5=CC=NC=C5)=CC=NC=C1 |
| InChIKey |
USWLOKMMUTWFMD-UHFFFAOYSA-N |
| InChI |
InChI=1S/C24H16N4S/c1-9-25-10-2-17(1)21-22(18-3-11-26-12-4-18)24(20-7-15-28-16-8-20)29-23(21)19-5-13-27-14-6-19/h1-16H |
| PubChem CID |
253078 |
| 靶点 |
Gli |
| 通路 |
Hedgehog;Stem Cells |
| 背景说明 |
GANT 58 是一种有效的 Gli 拮抗剂,抑制 GLI1 诱导的转录。 |
| 生物活性 |
GANT 58 (NSC 75503) is a potent GLI antagonist that inhibits GLI1-induced transcription with IC50 of 5 μM.[1-2] |
| IC50 |
IC50: 5 μM (Gli)[1] |
| In Vitro |
GANT58 是 Hh 信号的下游抑制剂。GANT58 是 Smo 和 Sufu 下游 Hh 信号的抑制剂。GANT58 主要作用于核水平，因为具有突变的核输出信号的 GLI1 诱导的转录仍然被阻断。GANT58 以 GLI 依赖性方式有效抑制体外肿瘤细胞增殖，并使用具有下游 Hh 通路激活的人前列腺癌细胞成功阻断细胞生长[1]。GANT58 (NSC75503) 已被证明可抑制 GLI1 (以及其他 GLI 物种) 的转录激活。GANT58 已被证明可以抑制 GLI 反式激活[2]。 |
| In Vivo |
裸鼠皮下注射 GLI1 阳性 22Rv1 前列腺癌细胞，形成肿瘤 (中值大小 ≈ 250 mm3)。裸鼠每天皮下注射浓度为 50 mg/kg 的环巴胺、GANT61、GANT58 或仅使用溶剂 (每组 n=4-5)，3 天后，环巴胺处理的动物在注射部位出现严重溃疡。因此，将处理方案更改为仅每隔一天注射一次。为了能够比较所有化合物，还为 GANT 引入了该方案，尽管用这些化合物处理的小鼠没有显示出此类毒性迹象。所有注射均在距肿瘤 2-3 厘米处进行。在 18 天的处理期间，观察到所有化合物都抑制了肿瘤细胞的生长。用环巴胺或 GANT58 处理可抑制额外的异种移植物生长并限制肿瘤大小的增加[1]。 |
| 细胞实验 |
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]. |
| 动物实验 |
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. |
| 数据来源文献 |
[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.
[2]. Joo J， et al. GLI1 is a central mediator of EWS/FLI1 signaling in Ewing tumors. PLoS One. 2009 Oct 27;4(10):e7608. |
| 规格 |
5mg 10mg 50mg 100mg |
| 单位 |
瓶 |
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