Gliotoxin
mRNA synthesis
In vitro transcription of capped mRNA with modified nucleotides and Poly(A) tail
Tyramide Signal Amplification (TSA)
TSA (Tyramide Signal Amplification), used for signal amplification of ISH, IHC and IC etc.
Phos Binding Reagent Acrylamide
Separation of phosphorylated and non-phosphorylated proteins without phospho-specific antibody
Cell Counting Kit-8 (CCK-8)
A convenient and sensitive way for cell proliferation assay and cytotoxicity assay
SYBR Safe DNA Gel Stain
Safe and sensitive stain for visualization of DNA or RNA in agarose or acrylamide gels.
Inhibitor Cocktails
Protect the integrity of proteins from multiple proteases and phosphatases for different applications.
Gliotoxin(胶霉毒素)是由烟曲霉菌和其它致病真菌合成的免疫抑制剂,抑制20S蛋白酶体的糜蛋白酶样活性[1]。
Gliotoxin可以抑制法尼基转移酶的活性,IC50值为80 μM,抑制异戊烯转移酶I,IC50值为17 μM,这些激起了研究者对该环硫二氧代哌嗪的潜在抗肿瘤活性的兴趣。另外,gliotoxin可以抑制六种乳腺癌细胞的增殖,mean ± SD IC50值为289 ± 328 M。而gliotoxinin以剂量依赖的方式抑制细胞内 LaminB的法呢酰化和Rap1 A的香叶酰香叶酰化[2]。
在N-甲基-N-亚硝基脲大鼠乳腺癌模型中进行随机对照研究,对10只动物每周皮下注射10 mg/ kg的gliotoxin,注射4周,与10只对照组相比,胶霉毒素具有明显的抗肿瘤活性,这支持了体外实验的结论,且gliotoxin的毒性较小,该单次剂量高达25 mg/kg时耐受性良好[2]。
与野生型菌株相比,烟曲霉突变体中,gliotoxin生成不足,导致较少的烟曲霉分生孢子内化进入A549细胞,但J774巨噬细胞的吞噬作用增加。1050 ng/ml浓度的Gliotoxin以剂量依赖的方式促进烟曲霉内化进入A549细胞,但抑制巨噬细胞吞噬,对A549细胞没有细胞毒性。此外,Gliotoxin能激活A549肺上皮细胞的PLD活性,通过这种方式有效的促进曲霉内化进入细胞。浓度范围从10到100 ng / ml的gliotoxin也被用于阻止A549上皮细胞中ROS的生成[3]。
参考文献:
1. Pahl HL, Krauss B, Schulze-Osthoff K, et al. The immunosuppressive fungal metabolite gliotoxin specifically inhibits transcription factor NF-kappaB. The Journal of Experimental Medicine, 1996 , 183(4):1829-1840.
2. Vigushin DM, Mirsaidi N, Brooke G, et al. Gliotoxin is a dual inhibitor of farnesyltransferase and geranylgeranyltransferase I with antitumor activity against breast cancer in vivo. MEDICAL ONCOLOGY, 2004, 21(1):21-30.
3. Jia XD, Chen FY, Pan WH, et al. Gliotoxin promotes Aspergillus fumigatus internalization into type II human pneumocyte A549 cells by inducing host phospholipase D activation. Microbes and infection / Institut Pasteur, 2014, 16(6):491-501.
- 1. Aguiar M,, et al. "Diagnosis of Aspergillosis in Horses." mBio 2022 Oct 26;13(5) PMID: 36125294
- 2. Mateusz Stoszko, Abdullah M.S. Al-Hatmi, et al. "Gliotoxin, identified from a screen of fungal metabolites, disrupts 7SK snRNP, releases P-TEFb and reverses HIV-1 latency." bioRxiv. 2019 November 20.
- 3. Angelina C, Tan ISY, et al. "KIF1Bβ increases ROS to mediate apoptosis and reinforces its protein expression through O (2)(-) in a positive feedback mechanism in neuroblastoma." Sci Rep. 2017 Dec 4;7(1):16867. PMID:29203804
Physical Appearance | A crystalline solid |
Storage | Desiccate at -20°C |
M.Wt | 326.38 |
Cas No. | 67-99-2 |
Formula | C13H14N2O4S2 |
Solubility | Soluble in DMSO |
Chemical Name | (3R,5aS,6S,10aR)-6-hydroxy-3-(hydroxymethyl)-2-methyl-2,3,5a,6-tetrahydro-1H-3,10a-epidithiopyrazino[1,2-a]indole-1,4(10H)-dione |
SDF | Download SDF |
Canonical SMILES | O[C@H]1C=CC=C2[C@@H]1N(C([C@@]3(N4C)CO)=O)[C@@](C4=O)(SS3)C2 |
运输条件 | 蓝冰运输或根据您的需求运输。 |
一般建议 | 不同厂家不同批次产品溶解度各有差异,仅做参考。若实验所需浓度过大至产品溶解极限,请添加助溶剂助溶或自行调整浓度。溶液形式一般不宜长期储存,请尽快用完。 |
细胞实验[1]: | |
细胞系 |
乳腺癌细胞系(MCF-7和MDA-MB-231细胞) |
溶解方法 |
该化合物在DMSO里面的溶解度>10mM。为了获得更高的浓度,可以将离心管在37℃加热10分钟和/或在超声波浴中震荡一段时间。原液可以在-20℃以下储存几个月。 |
反应条件 |
1 nM至10μM |
应用 |
Gliotoxin在同一浓度范围内抑制培养的六种乳腺癌细胞系的增殖和蛋白的异戊烯化反应。用gliotoxin处理24小时,导致乳腺癌细胞系中Lamin B法尼基化和Rap1A香叶基香叶基化明显的剂量依赖性抑制。总之,这些研究结果表明,在乳腺癌细胞系中观察到gliotoxin的抗肿瘤活性最可能是由于异戊烯转移酶抑制引起。 |
动物实验[2]: | |
动物模型 |
携带N-甲基-亚硝基脲(NMU)诱导的肿瘤的近交原代雌性(Ludwig / Wistar / Olac)大鼠 |
剂量 |
1.25至25mg / kg; 皮下注射; 每周一次,共4周 |
应用 |
在所有大鼠中,完成研究的所有五只gliotoxin处理大鼠均对给药作出反应,其中三只出现> 50%的肿瘤消退(部分反应),另两只具有稳定的疾病(<50%的肿瘤消退),并且gliotoxin的抗肿瘤作用在治疗的第一周内显现。 |
注意事项 |
请测试所有化合物在室内的溶解度,实际溶解度和理论值可能略有不同。这是由实验系统的误差引起的,属于正常现象。 |
References: [1]. Vigushin DM, Mirsaidi N, Brooke G., et al. Gliotoxin is a dual inhibitor of farnesyltransferase and geranylgeranyltransferase I with antitumor activity against breast cancer in vivo. MEDICAL ONCOLOGY, 2004, 21(1):21-30. |