CA-074 Me
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.
CA-074 Me是一种膜通透性的和选择性的cathepsin B抑制剂，IC50值为36.3 nM [1, 2]。
CA-074是CA-074的甲基酯衍生物。在培养的人牙龈成纤维细胞中，CA-074 Me抑制了95%的cathepsin B活性，而对cathepsins B和L的总活性仅表现出54%的部分抑制效应。在还原条件下，CA-074 Me也可以抑制cathespin L的活性。将纯化的人的cathepsin L用1.4 mM DTT或4.2 mM GSH预处理2小时后，CA-074 Me可以抑制超过90%的cathepsin L活性。除此之外，在1.4 mM DTT存在时，CA-074 Me可以完全抑制cathepsin B的活性 [2，3]。
参考文献：
[1] Wu X, Zhang L, Gurley E, et al. Prevention of free fatty acid–induced hepatic lipotoxicity by 18β-glycyrrhetinic acid through lysosomal and mitochondrial pathways. Hepatology, 2008, 47(6): 1905-1915.
[2] Steverding D. The cathepsin B-selective inhibitors CA-074 and CA-074Me inactivate cathepsin L under reducing conditions. Open Enzyme Inhibition Journal, 2011, 4: 11-16.
[3] Buttle D J, Murata M, Knight C G, et al. CA074 methyl ester: a proinhibitor for intracellular cathepsin B. Archives of biochemistry and biophysics, 1992, 299(2): 377-380.
- 1. Jianhua Wang, Lichun Wang, et al. "Cathepsin B aggravates acute pancreatitis by activating the NLRP3 inflammasome and promoting the caspase-1-induced pyroptosis." Int Immunopharmacol. 2021 May;94:107496. PMID:33639565
- 2. Zhi X, Zhang Y, et al. "NLRP3 inflammasome activation by Foot-and-mouth disease virus infection mainly induced by viral RNA and non-structural protein 2B." RNA Biol. 2020;17(3):335–349. PMID:31840571
- 3. Zhou H, Du R, et al. "Cannabinoid receptor 2 promotes the intracellular degradation of HMGB1 via the autophagy-lysosome pathway in macrophage." Int Immunopharmacol. 2020;78:106007. PMID:31806570
- 4. Chen CH, Bhasin S, et al. "Study of Cathepsin B inhibition in VEGFR TKI treated human renal cell carcinoma xenografts." Oncogenesis. 2019 Feb 22;8(3):15. PMID:30796200
- 5. Xu Z, Zhang Y, et al. "Novel half-sandwich iridium OˆC (carbene)-Complexes: In vitro and in vivo tumor growth suppression and pro-apoptosis via ROS-mediated cross-talk between mitochondria and lysosomes." Cancer Lett. 2019 Apr 10;447:75-85. PMID:30673591
- 6. Yan X, Li F, et al. "Interleukin-1beta released by microglia initiates the enhanced glutamatergic activity in the spinal dorsal horn during paclitaxel-associated acute pain syndrome." Glia. 2018 Dec 21. PMID:30578561
- 7. Gonzalez EA, Martins GR, et al. "Cathepsin B inhibition attenuates cardiovascular pathology in mucopolysaccharidosis I mice." Life Sci. 2018 Mar 1;196:102-109. PMID:29366749
- 8. Shao G, Wang R, et al. "The E3 ubiquitin ligase NEDD4 mediates cell migration signaling of EGFR in lung cancer cells." Mol Cancer. 2018 Feb 19;17(1):24. PMID:29455656
- 9. Clerc P, Jeanjean P, et al. "Targeted Magnetic Intra-Lysosomal Hyperthermia produces lysosomal reactive oxygen species and causes Caspase-1 dependent cell death." J Control Release. 2017 Dec 1;270:120-134. PMID:29203413
| Physical Appearance | A solid |
| Storage | Store at -20°C |
| M.Wt | 397.5 |
| Cas No. | 147859-80-1 |
| Formula | C19H31N3O6 |
| Solubility | insoluble in H2O; ≥19.88 mg/mL in DMSO; ≥51.5 mg/mL in EtOH with ultrasonic |
| Chemical Name | methyl (2S)-1-[(2S)-3-methyl-2-[[(2S,3S)-3-(propylcarbamoyl)oxirane-2-carbonyl]amino]pentanoyl]pyrrolidine-2-carboxylate |
| SDF | Download SDF |
| Canonical SMILES | CCCNC(=O)C1C(O1)C(=O)NC(C(C)CC)C(=O)N2CCCC2C(=O)OC |
| 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 |
McNtcp.24细胞 |
|
溶解方法 |
在DMSO中的溶解度>10 mM。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 |
0.1 µM，2小时 |
|
应用 |
在0.1 ?M CA-074 Me缺乏或存在时，细胞在单独培养基或含有50 ?M GCDC的培养基中培养。2小时孵育后对细胞凋亡进行定量。在McNtcp.24细胞中，组织蛋白酶B（cathepsin B）的抑制剂CA-074 Me减少GCDC介导的组织蛋白酶B活性的增加和细胞凋亡。该结果证实，在原代大鼠肝细胞中，组织蛋白酶B活性增加并有助于胆汁盐介导的细胞凋亡。 |
| 动物实验[2]： | |
|
动物模型 |
CatB+/+ 小鼠 |
|
剂量 |
4 mg/100 g；腹腔注射 |
|
应用 |
与注射生理盐水的对照小鼠相比，CA-074 Me预处理的catB+/+小鼠中TNF-α治疗后血清ALT的水平显著降低，肝组织结构得以保留，只有中度损伤。这些结果表明，药理学抑制cat B（组织蛋白酶B）的活性可能部分衰减TNF-α诱导的肝损伤。 |
|
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] Faubion W A, Guicciardi M E, Miyoshi H, et al. Toxic bile salts induce rodent hepatocyte apoptosis via direct activation of Fas. The Journal of clinical investigation, 1999, 103(1): 137-145. [2] Guicciardi M E, Miyoshi H, Bronk S F, et al. Cathepsin B knockout mice are resistant to tumor necrosis factor-α-mediated hepatocyte apoptosis and liver injury: implications for therapeutic applications. The American journal of pathology, 2001, 159(6): 2045-2054. |
|
| 描述 | CA-074 Me是一种细胞通透性的cathepsin B抑制剂。 | |||||
| 靶点 | cathepsin B | |||||
| IC50 | 2.2 nM | |||||
质量控制和MSDS
- 批次:
化学结构
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