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)[4].
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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.
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