Concanamycin A
(Synonyms: 刀豆素A; Antibiotic X 4357B; Folimycin; X 4357B) 目录号 : GC17519Concanamycin A 是液泡型 ATP 酶 (V-ATPase) 的特异性抑制剂，IC50 值为 10 nM 。
Cas No.:80890-47-7
Sample solution is provided at 25 µL, 10mM.
-
Related Biological Data
JAM1 is degraded by the autophagy pathway and negatively regulates RKN resistance. c, d Response of WT and atg7 mutant seedlings to the ubiquitin proteasome inhibitor MG132, the vacuolar-type ATPase inhibitor ConcanamycinA (ConA) and the autophagy inducer AZD8055 with or without RKN infection.
Plants were soaked in 0.5X Linsmaier and Skoog (LS) liquid medium containing DMSO, 50 μM MG132, 5 μM AZD8055 or 1 μM ConA (Glpbio, GC17519).
Nat Commun 14.1 (2023): 4769. PMID: 37553319 IF: 16.6009 -
Related Biological Data
ZmNBR1 is not phosphorylated by ZmBRI1a, and ZmNBR1 promotes the autophagic degradation of ZmBRI1a (F) Immunoblot analysis of the ZmBRI1a protein levels. Plants were grown to the three‐leaf stage and treated with 20% PEG6000 (dehydration stress) with or without concanamycin A (Conc A) (1 μmol/L) for 12 h.
For autophagy inhibitor treatment, dimethyl sulfoxide, spautin‐1, or Conc A (1 μmol/L; GLPBIO, Montclair, CA, USA) was added to the PEG6000 treatment for 12 h.
J Integr Plant Biol (2024). PMID: 38607264 IF: 11.3997
Quality Control & SDS
- View current batch:
- Purity: >98.00%
- COA (Certificate Of Analysis)
- SDS (Safety Data Sheet)
- Datasheet
| Cell experiment [1,2]: | |
|
Cell lines |
HCT-116, DLD-1, Colo206F, HeLa cells, Androgen-dependent (LNCaP) and androgen-independent (C4-2B) cells. |
|
Preparation method |
This compound is limited soluble in DMSO. General tips for obtaining a higher concentration: Please warm the tube at 37 ℃ for 10 minutes and/or shake it in the ultrasonic bath for a while. Stock solution can be stored below -20℃ for several months. |
|
Reacting condition |
20 nM, 60 min |
|
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%. |
|
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. |
|
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). |
|
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.
Concanamycin A 是液泡型 ATP 酶 (V-ATPase) 的特异性抑制剂，IC50 值为 10 nM [1]。
液泡型 ATP 酶 (V-ATPase) 由透明细胞表达以酸化附睾腔，这对男性生育能力至关重要；更重要的是，它诱导质子挤出到细胞外介质中，这有助于在酸性微环境下维持细胞内 pH 值。据报道，V-ATPase 还参与实体瘤周围/内部微环境的酸化过程，并在多种恶性肿瘤中诱导肿瘤侵袭/多药耐药。 [2].
刀豆霉素 A (CMA) 是一种特异性 V-ATPase 抑制剂，与报道的 V-ATPase 抑制剂 SS33410 不同。在口腔鳞状细胞癌 (OSCC) OSCC 细胞系（MISK81-5、SAS 和 HSC-4）中，低浓度的 CMA 处理可诱导肿瘤细胞凋亡 [3]。用刀豆霉素 A 预处理的结直肠癌细胞系可通过阻断 V-ATP 酶的内体酸化，显着增强肿瘤坏死因子 (TNF) 相关凋亡诱导配体 (TRAIL) 诱导的细胞凋亡 [4]。当用前列腺癌细胞系 C4-2B 进行测试时，刀豆霉素 A 对 V-ATPase 的抑制作用使体外侵袭降低了 80% [5]。
刀豆霉素 A 也被报道为通过穿孔素介导的细胞毒性途径的 CTL 细胞毒性的有效抑制剂 [6]。
| Cas No. | 80890-47-7 | SDF | |
| 别名 | 刀豆素A; Antibiotic X 4357B; Folimycin; X 4357B | ||
| 化学名 | (3Z,5E,7R,8R,9S,10S,11R,13E,15E,17S,18R)-18-[(1S,2R,3S)-3-[(2R,4R,5S,6R)-4-[[4-O-(aminocarbonyl)-2,6-dideoxy-β-D-arabino-hexopyranosyl]oxy]tetrahydro-2-hydroxy-5-methyl-6-(1E)-1-propen-1-yl-2H-pyran-2-yl]-2-hydroxy-1-methylbutyl]-9-ethyl-8,10-dihydroxy-3, | ||
| 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 | ||
| 分子式 | C46H75NO14 | 分子量 | 866.09 |
| 溶解度 | Methanol : 10 mg/mL (11.55 mM; Need ultrasonic and warming); DMSO : ≥ 10 mg/mL (11.55 mM) | 储存条件 | -20°C, protect from light, the product is provided in acetonitrile solution, avoid solvent volatilization. |
| 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 | 1.1546 mL | 5.7731 mL | 11.5461 mL |
| 5 mM | 0.2309 mL | 1.1546 mL | 2.3092 mL |
| 10 mM | 0.1155 mL | 0.5773 mL | 1.1546 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。