Decanoyl-RVKR-CMK (Synonyms: Furin Inhibitor I) |
| Catalog No.GC15108 |
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).
Products are for research use only. Not for human use. We do not sell to patients.
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, SchÄfer 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.
| 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: |
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| Cas No. | 150113-99-8 | SDF | |
| Synonyms | Furin Inhibitor I | ||
| Chemical Name | (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 | ||
| Formula | C34H66ClN11O5 | M.Wt | 744.42 |
| Solubility | 33mg/mL in ethanol, or in DMSO, or in DMF | Storage | Store at -20°C |
| General tips | Please select the appropriate solvent to prepare the stock solution according to the
solubility of the product in different solvents; once the solution is prepared, please store it in
separate packages to avoid product failure caused by repeated freezing and thawing.Storage method
and period of the stock solution: When stored at -80°C, please use it within 6 months; when stored
at -20°C, please use it within 1 month. To increase solubility, heat the tube to 37°C and then oscillate in an ultrasonic bath for some time. |
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| Shipping Condition | Evaluation sample solution: shipped with blue ice. All other sizes available: with RT, or with Blue Ice upon request. | ||
| Prepare stock solution | |||
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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 |
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Quality Control & SDS
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- Purity: >98.00%
- COA (Certificate Of Analysis)
- SDS (Safety Data Sheet)
- Datasheet
Average Rating: 5 (Based on Reviews and 18 reference(s) in Google Scholar.)
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