Concanamycin A
Concanamycin A is a specific inhibitor of vacuolar-type ATPase (V-ATPase) with IC50 value of 10 nM [1].
Vacuolar-type ATPase (V-ATPase) is expressed by clear cells to acidify the lumen of the epididymis, which is essential for male fertility; what's more, it induced proton extrusion into the extracellular medium which contributes to maintaining the intracellular pH under an acidic microenvironment. V-ATPase has also been reported to involve in the process of acidificating microenvironment around/in solid tumors and inducing tumor invasion/multi-drug resistance in several malignant tumors [2].
Concanamycin A (CMA) is a specific V-ATPase inhibitor and is different from the reported V-ATPase inhibitor SS33410. In oral squamous cell carcinoma (OSCC) OSCC cell lines (MISK81-5, SAS and HSC-4), low-concentration of CMA treatment induced the apoptosis of tumor cells [3]. Pretreated colorectal cancer cell lines with concanamycin A could significantly enhanced the Tumour necrosis factor (TNF) related apoptosis inducing ligand (TRAIL)-induced apoptosis by blocking endosomal acidification by V-ATPase [4]. When tested with prostate cancer cell line C4-2B, inhibition of V-ATPase by concanamycin A reduced 80% invasion in vitro [5].
Concanamycin A also had been reported as a potent inhibitor of CTL cytotoxicity via perforin-mediated cytotoxic pathway [6].
References:
[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. Pengwei Wang, et al. "Exo84c-regulated degradation is involved in the normal self-incompatible response in Brassicaceae." Cell Rep. 2024 Mar 26;43(3):113913. PMID: 38442016
- 2. Ling-Yan Wang, Jian Li, et al. "Orosomucoid proteins limit endoplasmic reticulum stress in plants." New Phytol. 2023 Aug 22. PMID: 37606093
- 3. Du-Hwa Lee, Ilyeong Choi, et al. "Three consecutive cytosolic glycolysis enzymes modulate autophagic flux." Plant Physiol. 2023 Aug 4;kiad439. PMID: 37539947
- 4. Chen Wan, Hui Zhang, et al. "Selective autophagy regulates chloroplast protein import and promotes plant stress tolerance." EMBO J. 2023 Jul 17;42(14):e112534. PMID: 37248861
- 5. 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
- 6. 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 |
| Shipping Condition | Small Molecules with Blue Ice, Modified Nucleotides with Dry Ice. |
| General tips | We do not recommend long-term storage for the solution, please use it up soon. |
| Cell experiment [1,2]: | |
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Cell lines |
HCT-116, DLD-1, Colo206F, HeLa cells, Androgen-dependent (LNCaP) and androgen-independent (C4-2B) cells. |
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Preparation method |
This compound is limited soluble in DMSO. General tips for obtaining a higher concentration: Please warm the tube at 37°C?for 10 minutes and/or shake it in the ultrasonic bath for a while. Stock solution can be stored below -20°C for several months. |
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Reacting condition |
20 nM, 60 min |
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Applications |
CCA effectively attenuated the TRAIL-induced activation of caspases in TRAIL-sensitive colorectal cancer cell lines. In CCA-treated Colo206F cells, the number of M30-positive apoptotic cells gradually increased and almost reached the proportion seen in untreated cells within 3–4h after the addition of TRAIL. Treatment with CCA resulted in a lack of apoptosis-related chromatin condensation in DLD-1 cells incubated with TRAIL for 90 min. Treatment with nanomolar concentrations of concanamycin A reduced the in vitro invasion in LNCaP and C4-2B cell types by 80%. |
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Other notes |
Please test the solubility of all compounds indoor, and the actual solubility may slightly differ with the theoretical value. This is caused by an experimental system error and it is normal. |
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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). |
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