CA 074
![mRNA synthesis](/media/diy/images/page/figure1-mrna.png)
mRNA synthesis
In vitro transcription of capped mRNA with modified nucleotides and Poly(A) tail
![Tyramine Signal Amplification (TSA)](/media/diy/images/page/figure2-01.png)
Tyramide Signal Amplification (TSA)
TSA (Tyramide Signal Amplification), used for signal amplification of ISH, IHC and IC etc.
![screening library](/media/diy/images/page/figure3-01.png)
Phos Binding Reagent Acrylamide
Separation of phosphorylated and non-phosphorylated proteins without phospho-specific antibody
![Cell Counting Kit-8 (CCK-8)](/media/diy/images/page/CCK-8.jpg)
Cell Counting Kit-8 (CCK-8)
A convenient and sensitive way for cell proliferation assay and cytotoxicity assay
![SYBR Safe DNA Gel Stain](/media/diy/images/page/SYBR Safe DNA Gel Stain.png)
SYBR Safe DNA Gel Stain
Safe and sensitive stain for visualization of DNA or RNA in agarose or acrylamide gels.
![Inhibitor Cocktails](/media/diy/images/page/Inhibitor Cocktails.jpg)
Inhibitor Cocktails
Protect the integrity of proteins from multiple proteases and phosphatases for different applications.
CA-074是一种特异性组织蛋白酶B抑制剂,可消除Abeta42活化的BV2细胞引起的神经毒性效应[1]。经组织蛋白酶B抑制剂CA-074 或者Z-FA-FMK处理的培养基可抑制TPA抑制细胞生长的作用以及尿激酶原的活化[2]。CA-074给药可抑制对外源性抗原的反应,如乙肝病毒抗原、卵白蛋白和硕大利什曼原虫抗原,并诱导辅助T细胞反应的转换,CD4+ T细胞从Th2细胞转变为Th1细胞,从而下调IgE和IgG1的产生[3]。
在catB(+/+)小鼠中,CA-074 Me通过药理学抑制组织蛋白酶B,可减少肿瘤坏死因子α(TNF-α)诱导的肝损伤[4]。
组织蛋白酶B抑制剂E-64、CA-074和vitamin B6可强烈抑制Th-2型免疫反应。
参考文献:
[1] Identification of cathepsin B as a mediator of neuronal death induced by Abeta-activated microglial cells using a functional genomics approach. Gan, L., Ye, S., Chu, A., Anton, K., Yi, S., Vincent, V.A., von Schack, D., Chin, D., Murray, J., Lohr, S., Patthy, L., Gonzalez-Zulueta, M., Nikolich, K., Urfer, R. J. Biol. Chem. (2004)
[2] Phorbol ester activation of a proteolytic cascade capable of activating latent transforming growth factor-betaL a process initiated by the exocytosis of cathepsin B. Guo, M., Mathieu, P.A., Linebaugh, B., Sloane, B.F., Reiners, J.J. J. Biol. Chem. (2002)
[3] Insights into the roles of cathepsins in antigen processing and presentation revealed by specific inhibitors. Katunuma, N., Matsunaga, Y., Himeno, K., Hayashi, Y. Biol. Chem. (2003)
[4] Cathepsin B knockout mice are resistant to tumor necrosis factor-alpha-mediated hepatocyte apoptosis and liver injury: implications for therapeutic applications. Guicciardi, M.E., Miyoshi, H., Bronk, S.F., Gores, G.J. Am. J. Pathol. (2001)
- 1. Lei-Bo Xu, Yu-Fei Qin, et al. "Cathepsin-facilitated invasion of BMI1-high hepatocellular carcinoma cells drives bile duct tumor thrombi formation." Nat Commun. 2023 Nov 3;14(1):7033. PMID: 37923799
- 2. Zhijun Liu, Himani Nailwal, et al. "A class of viral inducer of degradation of the necroptosis adaptor RIPK3 regulates virus-induced inflammation." Immunity. 2021 Feb 9;54(2):247-258.e7. PMID: 33444549
- 3. Zhang W, Fan W, et al. "Development of Improved Tumor-Residualizing, GRPR-Targeted Agents: Preclinical Comparison of an Endolysosomal Trapping Approach in Agonist and Antagonistic Constructs." J Nucl Med. 2019 Oct 10. pii: jnumed.119.231282. PMID: 31601697
- 4. Sun N, Wang D, et al. "pH-dependent and cathepsin B activable CaCO(3) nanoprobe for targeted in vivo tumor imaging." Int J Nanomedicine. 2019 Jun 13;14:4309-4317. PMID: 31354262
- 5. Ju L, Han J, et al. "Obesity-associated inflammation triggers an autophagy-lysosomal response in adipocytes and causes degradation of perilipin 1."Cell Death Dis. 2019 Feb 11;10(2):121. PMID: 30741926
- 6. Zhang J, Wang J, et al. "Curcumin targets the TFEB-lysosome pathway for induction of autophagy. "Oncotarget. 2016 Sep 28. PMID: 27689333
Storage | Store at -20°C |
M.Wt | 383.44 |
Cas No. | 134448-10-5 |
Formula | C18H29N3O6 |
Synonyms | CA-074,CA074 |
Solubility | ≥19.17 mg/mL in DMSO; ≥31.3 mg/mL in EtOH; ≥5.91 mg/mL in H2O with ultrasonic |
Chemical Name | (2S)-1-[(2S,3S)-3-methyl-2-[[(3S)-3-(propylcarbamoyl)oxirane-2-carbonyl]amino]pentanoyl]pyrrolidine-2-carboxylic acid |
SDF | Download SDF |
Canonical SMILES | CCCNC(=O)C1C(O1)C(=O)NC(C(C)CC)C(=O)N2CCCC2C(=O)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]: | |
细胞系 |
人类脐静脉内皮细胞(HUVECs) |
溶解方法 |
该化合物在DMSO中的溶解度大于10 mM。若配制更高浓度的溶液,一般步骤如下:请将试管置于37℃加热10分钟和/或将其置于超声波浴中震荡一段时间。原液于-20℃可放置数月。 |
反应条件 |
24 h;10 mM |
实验结果 |
CA-074是组织蛋白酶B的特异性抑制剂,10 mM的CA-074对HUVEC细胞活力的影响为96.9±1.2%,其膜可渗透类似物CA-074-Me对HUVEC细胞活力的影响为101.7±0.4%,可忽略不计,类似于10mM米诺环素的效果(102.3±2.6%)。 |
动物实验[2]: | |
动物模型 |
雌性Balb/c小鼠 |
剂量 |
50 mg/kg;腹膜内注射 |
实验结果 |
为了测试半胱氨酸蛋白酶抑制剂的在体疗效,我们使用选择性CA-074抑制剂治疗4T1.2肿瘤小鼠。抑制剂对4T1.2荷瘤小鼠的原发性肿瘤生长没有影响。然而,转移分析显示化合物之间存在显著差异。CA-074显著减少转移到肺(P < 0.05)和骨(P <0.05)的肿瘤细胞。 |
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] Premzl A, Turk V, Kos J. Intracellular proteolytic activity of cathepsin B is associated with capillary‐like tube formation by endothelial cells in vitro[J]. Journal of cellular biochemistry, 2006, 97(6): 1230-1240. [2] Withana N P, Blum G, Sameni M, et al. Cathepsin B inhibition limits bone metastasis in breast cancer[J]. Cancer research, 2012, 72(5): 1199-1209. |
CA 074是一种组织蛋白酶B(Cathepsin B)抑制剂(Ki = 2-5 nM),比对组织蛋白酶H和L的选择性高(Ki = 40-200 μM),可减少4T1.2乳腺癌模型中的骨转移。 | ||||||
靶点 | cathepsin B | |||||
Ki | 2-5nM |
质量控制和MSDS
- 批次:
化学结构
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