Decanoyl-RVKR-CMK
(Synonyms: Furin Inhibitor I) 目录号 : GC15108
Decanoyl-RVKR-CMK 是一种枯草杆菌蛋白酶/Kex2p 样前蛋白转化酶抑制剂；阻断所有七种转化酶（PC1、PC2、PC4、PACE4、PC5、PC7 和弗林蛋白酶）的活性。
Cas No.:150113-99-8
Sample solution is provided at 25 µL, 10mM.
Decanoyl-RVKR-CMK is a subtilisin/Kex2p-like proprotein convertase inhibitor; blocks activity of all seven convertases (PC1, PC2, PC4, PACE4, PC5, PC7 and furin)[4]. Decanoyl-RVKR-CMK inhibits cleavage of SARS-CoV-2 spike protein by furin and blocks viral cell entry (IC50 ? = 57 nM in plaque reduction assay)[9].
PC12 cells were treated with the PC enzyme inhibitor Decanoyl-RVKR-CMK to partially block the regulated release of VGF. VGF treatment in cell extracts and culture medium from Decanoyl-RVKR-CMK-treated PC12 reduced the culture, indicating extensive inhibition of invertase activity at these Decanoyl-RVKR-CMK concentrations[2]. Decanoyl-RVKR-CMK inhibits cleavage of glycoprotein B of human cytomegalovirus[8]. Decanoyl-RVKR-CMK promotes ciliated cell differentiation and has no effect on the ciliary beat frequency in air-liquid interface (ALI) cultures of human nasal epithelial cells (HNECs). CMK considerably increases ciliogenesis-related gene expression. CMK inhibited Notch1 processing and promoted regeneration and ciliogenesis of the mouse nasal respiratory epithelium after ZnSO4 injury[7]. In LoVo cell, Decanoyl-RVKR-CMK strongly reduced the recovery of sAPPα, Overexpression of Decanoyl-RVKR-CMK at high concentrations did not completely eliminate sAPP α-secretion[3]. Decanoyl-RVKR-CMK blocked entry of MERS-CoV harboring an S protein lacking furin cleavage sites; it even blocked entry into furin-deficient LoVo cells. In addition, Decanoyl-RVKR-CMK inhibited not only the enzymatic activity of furin but also those of cathepsin L, cathepsin B, trypsin, papain, and TMPRSS2[5]. Decanoyl-RVKR-CMK inhibits HIV-2ROD replication by blocking envelope glycoprotein precursor processing in the Jurkat lymphocyte cell[1].
When used Decanoyl-RVKR-CMK. PACE4 activity in skin squamous cell carcinoma cell lines resulted in impaired insulin-like growth factor 1 receptor maturation, diminished its intrinsic tyrosine kinase activity, and decreased tumor cell proliferation. Two-stage skin chemical carcinogenesis experiments, together with topical applications of CMK, demonstrated that Decanoyl-RVKR-CMK markedly reduced tumor incidence, tumor multiplicity, and metastasis, pointing to a significant delay in tumor progression in wild-type and PACE4 transgenic mice[6].
References:
[1]:Bahbouhi B, Bendjennat M, et,al. Inhibition of HIV-2(ROD) replication in a lymphoblastoid cell line by the alpha1-antitrypsin Portland variant (alpha1-PDX) and the decRVKRcmk peptide: comparison with HIV-1(LAI). Microbes Infect. 2001 Nov;3(13):1073-84. doi: 10.1016/s1286-4579(01)01467-8. PMID: 11709287.
[2]: Garcia AL, Han SK, et,al. A prohormone convertase cleavage site within a predicted alpha-helix mediates sorting of the neuronal and endocrine polypeptide VGF into the regulated secretory pathway. J Biol Chem. 2005 Dec 16;280(50):41595-608. doi: 10.1074/jbc.M509122200. Epub 2005 Oct 12. PMID: 16221685.
[3]: Lopez-Perez E, Zhang Y, et,al. Constitutive alpha-secretase cleavage of the beta-amyloid precursor protein in the furin-deficient LoVo cell line: involvement of the pro-hormone convertase 7 and the disintegrin metalloprotease ADAM10. J Neurochem. 2001 Mar;76(5):1532-9. doi: 10.1046/j.1471-4159.2001.00180.x. PMID: 11238737.
[4]: Fugère M, Day R. Cutting back on pro-protein convertases: the latest approaches to pharmacological inhibition. Trends Pharmacol Sci. 2005 Jun;26(6):294-301. doi: 10.1016/j.tips.2005.04.006. PMID: 15925704; PMCID: PMC7119077.
[5]: Matsuyama S, Shirato K, et,al. Middle East Respiratory Syndrome Coronavirus Spike Protein Is Not Activated Directly by Cellular Furin during Viral Entry into Target Cells. J Virol. 2018 Sep 12;92(19):e00683-18. doi: 10.1128/JVI.00683-18. PMID: 30021905; PMCID: PMC6146822.
[6]: Bassi DE, Zhang J, et,al. Proprotein convertase inhibition results in decreased skin cell proliferation, tumorigenesis, and metastasis. Neoplasia. 2010 Jul;12(7):516-26. doi: 10.1593/neo.92030. PMID: 20651981; PMCID: PMC2907578.
[7]: Lee SN, Choi IS, Kim HJ, Yang EJ, Min HJ, Yoon JH. Proprotein convertase inhibition promotes ciliated cell differentiation - a potential mechanism for the inhibition of Notch1 signalling by decanoyl-RVKR-chloromethylketone. J Tissue Eng Regen Med. 2017 Sep;11(9):2667-2680. doi: 10.1002/term.2240. Epub 2016 Nov 22. PMID: 27878968; PMCID: PMC6214225.
[8]:Vey M, Sch?fer W, et,al. Proteolytic processing of human cytomegalovirus glycoprotein B (gpUL55) is mediated by the human endoprotease furin. Virology. 1995 Jan 10;206(1):746-9. doi: 10.1016/s0042-6822(95)80002-6. PMID: 7726996.
[9]:Cheng YW, Chao TL, et,al. Furin Inhibitors Block SARS-CoV-2 Spike Protein Cleavage to Suppress Virus Production and Cytopathic Effects. Cell Rep. 2020 Oct 13;33(2):108254. doi: 10.1016/j.celrep.2020.108254. Epub 2020 Sep 23. PMID: 33007239; PMCID: PMC7510585.
Decanoyl-RVKR-CMK 是一种枯草杆菌蛋白酶/Kex2p 样前蛋白转化酶抑制剂；阻断所有七种转化酶（PC1、PC2、PC4、PACE4、PC5、PC7 和弗林蛋白酶）的活性[4]。癸酰基-RVKR-CMK 抑制弗林蛋白酶对 SARS-CoV-2 刺突蛋白的切割并阻断病毒细胞进入（IC50 = 57 nM，在噬菌斑减少试验中）[9] .
PC12 细胞用 PC 酶抑制剂 Decanoyl-RVKR-CMK 处理，以部分阻断 VGF 的调节释放。来自癸酰基-RVKR-CMK 处理的 PC12 的细胞提取物和培养基中的 VGF 处理减少了培养物，表明在这些癸酰基-RVKR-CMK 浓度下对转化酶活性的广泛抑制[2]。 Decanoyl-RVKR-CMK 抑制人巨细胞病毒糖蛋白 B 的裂解[8]。 Decanoyl-RVKR-CMK 促进纤毛细胞分化，并且对人鼻上皮细胞 (HNEC) 的气液界面 (ALI) 培养物中的纤毛搏动频率没有影响。 CMK 显着增加与纤毛发生相关的基因表达。 CMK 抑制 Notch1 加工，促进 ZnSO4 损伤后小鼠鼻呼吸道上皮的再生和纤毛生成[7]。在 LoVo 细胞中，Decanoyl-RVKR-CMK 强烈降低了 sAPPα 的恢复，高浓度 Decanoyl-RVKR-CMK 的过表达并没有完全消除 sAPP α-分泌[3]。癸酰基-RVKR-CMK 阻断含有缺乏弗林蛋白酶切割位点的 S 蛋白的 MERS-CoV 的进入；它甚至阻止进入缺乏弗林蛋白酶的 LoVo 细胞。此外，Decanoyl-RVKR-CMK 不仅抑制弗林蛋白酶的酶活性，还抑制组织蛋白酶 L、组织蛋白酶 B、胰蛋白酶、木瓜蛋白酶和 TMPRSS2[5] 的酶活性。 Decanoyl-RVKR-CMK 通过阻断 Jurkat 淋巴细胞中的包膜糖蛋白前体加工来抑制 HIV-2ROD 复制[1]。
当使用 Decanoyl-RVKR-CMK 时。皮肤鳞状细胞癌细胞系中的 PACE4 活性导致胰岛素样生长因子 1 受体成熟受损，降低其内在酪氨酸激酶活性，并减少肿瘤细胞增殖。两阶段皮肤化学致癌实验以及 CMK 的局部应用表明，癸酰基-RVKR-CMK 显着降低了肿瘤发生率、肿瘤多样性和转移，表明野生型和 PACE4 转基因小鼠的肿瘤进展显着延迟< sup>[6].
| Cell experiment [1]: | |
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Cell lines |
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Preparation Method |
PC12 cells were rinsed with serum-free medium and treated with serum-free medium (with or without 100 µm Decanoyl-RVKR-CMK) for 3 h (basal release) and finally with serum-free medium containing 50 mm KCl (with or without 100 µm Decanoyl-RVKR-CMK) for 3 h. |
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Reaction Conditions |
100 µm Decanoyl-RVKR-CMK for 3h |
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Applications |
PC12 cells were treated with the PC enzyme inhibitor Decanoyl-RVKR-CMK to partially block the regulated release of VGF. VGF treatment in cell extracts and culture medium from Decanoyl-RVKR-CMK-treated PC12 reduced the culture, indicating extensive inhibition of invertase activity at these Decanoyl-RVKR-CMK concentrations. |
| Animal experiment [2]: | |
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Animal models |
K5-PACE4 transgenic mice |
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Preparation Method |
In mice topically treated with the hyperplasiogenic phorbol ester 12-O-tetradecanoylphorbol-13-acetate (TPA), a 2-day topical treatment of Decanoyl-RVKR-CMK at 300 uM. |
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Dosage form |
Decanoyl-RVKR-CMK was locally treated at 300 µM for 2 days; Once daily for 3 weeks |
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Applications |
When used Decanoyl-RVKR-CMK. PACE4 activity in skin squamous cell carcinoma cell lines resulted in impaired insulin-like growth factor 1 receptor maturation, diminished its intrinsic tyrosine kinase activity, and decreased tumor cell proliferation. Two-stage skin chemical carcinogenesis experiments, together with topical applications of CMK, demonstrated that Decanoyl- Decanoyl-RVKR-CMK markedly reduced tumor incidence, tumor multiplicity, and metastasis, pointing to a significant delay in tumor progression in wild-type and PACE4 transgenic mice. |
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References: [1]: Garcia AL, Han SK, et,al. A prohormone convertase cleavage site within a predicted alpha-helix mediates sorting of the neuronal and endocrine polypeptide VGF into the regulated secretory pathway. J Biol Chem. 2005 Dec 16;280(50):41595-608. doi: 10.1074/jbc.M509122200. Epub 2005 Oct 12. PMID: 16221685. |
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| Cas No. | 150113-99-8 | SDF | |
| 别名 | Furin Inhibitor I | ||
| 化学名 | (2S,5R,8R,11S)-5-(4-aminobutyl)-2,11-bis(3-((diaminomethylene)amino)propyl)-8-isopropyl-4,7,10,13-tetraoxo-3,6,9,12-tetraazatricosan-1-oyl chloride | ||
| Canonical SMILES | ClC([C@H](CCC/N=C(N)\N)NC([C@@H](CCCCN)NC([C@@H](C(C)C)NC([C@H](CCC/N=C(N)\N)NC(CCCCCCCCCC)=O)=O)=O)=O)=O | ||
| 分子式 | C34H66ClN11O5 | 分子量 | 744.42 |
| 溶解度 | 33mg/mL in ethanol, or in DMSO, or in DMF | 储存条件 | Store at -20°C |
| 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。 |
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| 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 | |||
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1 mg | 5 mg | 10 mg |
| 1 mM | 1.3433 mL | 6.7166 mL | 13.4333 mL |
| 5 mM | 0.2687 mL | 1.3433 mL | 2.6867 mL |
| 10 mM | 0.1343 mL | 0.6717 mL | 1.3433 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。
Quality Control & SDS
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- Purity: >98.00%
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