Concanamycin A
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.
Concanamycin A是液泡型ATP酶(V-ATP酶)的特异性抑制剂,IC50值为10 nM [1]。
液泡型ATP酶(V-ATP酶)在透明细胞中表达,可以酸化附睾的内腔,这对于男性生育能力是必不可少的。更重要的是,它可以引起质子在细胞外基质的积累,这对于在酸性微环境中维持细胞内pH具有重要作用。有报道称,在几种恶性肿瘤中,V-ATP酶参与酸化实体瘤周围的微环境及诱导肿瘤浸润/多药耐药性 [2]。
Concanamycin A(CMA)是特异性的V-ATP酶抑制剂,与之前报道的V-ATP酶抑制剂SS33410不同。在口腔鳞状细胞癌(OSCC)细胞系(MRSK81-5、SAS和HSC-4)中,低浓度CMA诱导肿瘤细胞的凋亡 [3]。使用concanamycin A预处理结直肠癌细胞系可以通过阻断V-ATP酶诱导的内含体酸化,显著增强肿瘤坏死因子(TNF)相关凋亡诱导配体(TRAIL)诱导的细胞凋亡 [4]。Concanamycin A通过抑制前列腺癌细胞系C4-2B细胞中的V-ATP酶,可以减少80%肿瘤浸润 [5]。
研究表明,Concanamycin A 通过穿孔素介导的细胞毒性途径,可以有效抑制CTL细胞毒性 [6]。
参考文献:
[1].Huss, M., et al., Concanamycin A, the specific inhibitor of V-ATPases, binds to the V(o) subunit c. J Biol Chem, 2002. 277(43): p. 40544-8.
[2].Muroi, M., et al., Folimycin (concanamycin A), a specific inhibitor of V-ATPase, blocks intracellular translocation of the glycoprotein of vesicular stomatitis virus before arrival to the Golgi apparatus. Cell Struct Funct, 1993. 18(3): p. 139-49.
[3].Kiyoshima, T., et al., Chemoresistance to concanamycin A1 in human oral squamous cell carcinoma is attenuated by an HDAC inhibitor partly via suppression of Bcl-2 expression. PLoS One, 2013. 8(11).
[4]. Horova V, et al., Inhibition of vacuolar ATPase attenuates the TRAIL-induced activation of caspase-8 and modulates the trafficking of TRAIL receptosomes. FEBS J, 2013. 280(14).
[5]. Michel V, et al., Inhibitors of vacuolar ATPase proton pumps inhibit human prostate cancer cell invasion and prostate-specific antigen expression and secretion. Int J Cancer. 2013.132(2).
[6]. Benkhoucha M et al., The neurotrophic hepatocyte growth factor attenuates CD8+ cytotoxic T-lymphocyte activity. J Neuroinflammation. 2013, 10.
- 1. Ye Chen, Xiao Wu, et al. "Amino acid starvation-induced LDLR trafficking accelerates lipoprotein endocytosis and LDL clearance." EMBO Rep. 2022 Feb 3;23(3):e53373. PMID: 34994492
- 2. Zhang G, Xu M, et al. "Up-regulation of granzyme B and perforin by staphylococcal enterotoxin C2 mutant induces enhanced cytotoxicity in Hepa1-6 cells." Toxicol Appl Pharmacol. 2016 Dec 15;313:1-9. PMID: 27742270
Physical Appearance | A solution in acetonitrile. To change the solvent, simply evaporate the acetonitrile under a gentle stream of nitrogen and immediately add the solvent of choice. |
Storage | Store at -20°C |
M.Wt | 866.09 |
Cas No. | 80890-47-7 |
Formula | C46H75NO14 |
Solubility | Limited solubility, soluble in DMSO |
SDF | Download SDF |
Canonical SMILES | CCC1C(C(CC(=CC=CC(C(OC(=O)C(=CC(=CC(C1O)C)C)OC)C(C)C(C(C)C2(CC(C(C(O2)C=CC)C)OC3CC(C(C(O3)C)OC(=O)N)O)O)O)OC)C)C)O |
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 [1,2]: | |
细胞系 |
HCT-116,DLD-1,Colo206F,HeLa细胞,雄激素依赖性(LNCaP)和雄激素非依赖性(C4-2B)细胞 |
溶解方法 |
该化合物在DMSO中的溶解度有限。若获取更高浓度的溶液,可在37°C下孵育10分钟,随后在超声波浴中摇匀。-20°C以下可储存数月。 |
反应条件 |
20 nM,60 min |
应用 |
在TRAIL敏感型结肠直肠癌细胞系中,CCA有效减弱TRAIL诱导的caspase的激活。在CCA处理的Colo206F细胞中,添加TRAIL后3-4h内M30阳性凋亡细胞数量逐渐增加,几乎达到未处理细胞的比例。在用TRAIL孵育90分钟的DLD-1细胞中,CCA引起凋亡相关的染色质凝聚缺乏。在LNCaP和C4-2B细胞中,纳摩尔浓度的CCA将体外侵袭减少80%。 |
注意事项 |
由于实验环境的不同,实际溶解度可能与理论值略有不同,请测试室内所有化合物的溶解度。 |
References: [1]. Horova V, et al., Inhibition of vacuolar ATPase attenuates the TRAIL-induced activation of caspase-8 and modulates the trafficking of TRAIL receptosomes. FEBS J, 2013. 280(14). [2]. Michel V, et al., Inhibitors of vacuolar ATPase proton pumps inhibit human prostate cancer cell invasion and prostate-specific antigen expression and secretion. Int J Cancer. 2013.132(2). |