1、Hotline: 400-820-3792Inhibitors Agonists Screening Librarieswww.MedChemEAlisporivirCat. No.: HY-12559CAS No.: 254435-95-5Synonyms: DEB-025; Debio-025; UNIL-025分式: CHNO分量: 1216.64作靶點(diǎn): HCV作通路: Anti-infection儲存式: Powder -20C 3 years4C 2 yearsIn solvent -80C 6 months-20C 1 month溶解性數(shù)據(jù)體外實(shí)驗(yàn) DMSO : 100 mg/m

2、L (82.19 mM)* means soluble, but saturation unknown.Mass Solvent1 mg 5 mg 10 mg Concentration制備儲備液1 mM 0.8219 mL 4.1097 mL 8.2194 mL5 mM 0.1644 mL 0.8219 mL 1.6439 mL10 mM 0.0822 mL 0.4110 mL 0.8219 mL請根據(jù)產(chǎn)品在不同溶劑中的溶解度，選擇合適的溶劑配制儲備液，并請注意儲備液的保存式和期限。體內(nèi)實(shí)驗(yàn) 請根據(jù)您的實(shí)驗(yàn)動物和給藥式選擇適當(dāng)?shù)娜芙獍福渲魄罢埾扰渲瞥蔚膬湟海僖来翁砑又軇?為保證實(shí)驗(yàn)結(jié)

3、果的可靠性，體內(nèi)實(shí)驗(yàn)的作液，建議您現(xiàn)現(xiàn)配，當(dāng)天使；澄的儲備液可以根據(jù)儲存條件，適當(dāng)保存；以下溶劑前的百分指該溶劑在您配制終溶液中的體積占)：1. 請依序添加每種溶劑： 10% DMSO 40% PEG300 5% Tween-80 45% salineSolubility: 2.5 mg/mL (2.05 mM); Clear solution1/3 Master of Small Molecules 您邊的抑制劑師www.MedChemEBIOLOGICAL ACTIVITY物活性 Alisporivir (DEB-025; Debio-025)親環(huán)蛋抑制劑，具有效的抗丙型肝炎病毒 (HCV

4、) 活性的。體外研究 DEB025 binds to CypA, a peptidyl-prolyl cis-trans isomerase which is a crucial cofactor for HCV replication1. Alisporivir (Debio-025) is an analogue of cyclosporine A and represents the prototype of a new class ofnon-immunosuppressive cyclophilin inhibitors. Alisporivir prevents HCV prote

5、in-mediated collapse of therespiration-driven mitochondrial membrane potential. Alisporivir prevents HCV protein-mediatedmitochondrial dysfunction outside the context of apoptosis, calcium overload, production of ROS, dysfunction2. In cell culture models, low-micromolar doses of alisporivir block SA

6、RS-CoV and MERS-CoV replication.Combination treatment with alisporivir and ribavirin increases the anti-MERS-CoV activity in cell culture 3.Alisporivir pretreatment stimulates antigen presentation by hepatoma target cells, leading to enhancement ofantigen-specific CD8+ T cell activation by 40%. Alis

7、porivir induces an increase of MHC-I and beta-2microglobulin on the surface of several cell lines 4.體內(nèi)研究 Combination treatment with alisporivir and ribavirin does not protect against SARS-CoV infection in a mousemodel 3.PROTOCOLCell Assay 2 Alisporivir is prepared in DMSO at 4 mM and diluted in cell

8、 culture medium at the indicated concentrations(0.1, 0.2, 0.3, 0.4, 0.5 M). UHCV-32 and UHCVcon-57.3 are U-2 OS human osteosar coma-derived celllines inducibly expressing the entire open reading frame derived from the HCV H77 prototype and consensusclones, respectively. Cell viability is measured by

9、 trypan blue exclusion analysis. HCV protein expression inthese cells is induced by withdrawal of tetracycline from the culture medium. The effect of tetracycline on thenaive U2 OS cell line is tested measuring mitochondria-related respiration and reactive oxygen species(ROS) production, which remai

10、ns unchanged 2.MCE has not independently confirmed the accuracy of these methods. They are for reference only. Cell Signal. 2019 May 4. pii: S0898-6568(19)30098-1.See more customer validations on HYPERLINK / www.MedChemEREFERENCES1. Coelmont L, et al. DEB025 (Alisporivir) inhibits hepatitis C virus

11、replication by preventing a cyclophilin A induced cis-trans isomerisationin domain II of NS5A. PLoS One. 2010 Oct 27;5(10):e13687.2. Quarato G, et al. The cyclophilin inhibitor alisporivir prevents hepatitis C virus-mediated mitochondrial dysfunction. Hepatology. 2012May;55(5):1333-43.3. de Wilde AH

12、, et al. Alisporivir inhibits MERS- and SARS-coronavirus replication in cell culture, but not SARS-coronavirus infection in amouse model. Virus Res. 2017 Jan 15;228:7-13.2/3 Master of Small Molecules 您邊的抑制劑師www.MedChemE4. Esser-Nobis K, et al. The cyclophilin-inhibitor alisporivir stimulates antigen presentation thereby promoting antigen-specific CD8(+) T cellactivation. J Hepatol. 2016 Jun;64(6):1305-14.McePdfHeightCaut