1、Hotline: 400-820-3792Inhibitors Agonists Screening Librarieswww.MedChemECenicriviroc MesylateCat. No.: HY-14882ACAS No.: 497223-28-6Synonyms: TAK-652 Mesylate; TBR-652 Mesylate分式: CHNOS分量: 793.05作靶點: CCR; HIV作通路: GPCR/G Protein; Immunology/Inflammation; Anti-infection儲存式: Powder -20C 3 years4C 2 yea

2、rsIn solvent -80C 6 months-20C 1 month溶解性數據體外實驗 DMSO : 107.5 mg/mL (135.55 mM)* means soluble, but saturation unknown.Mass Solvent1 mg 5 mg 10 mg Concentration制備儲備液1 mM 1.2610 mL 6.3048 mL 12.6095 mL5 mM 0.2522 mL 1.2610 mL 2.5219 mL10 mM 0.1261 mL 0.6305 mL 1.2610 mL請根據產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

3、意儲備液的保存式和期限。體內實驗 請根據您的實驗動物和給藥式選擇適當的溶解案，配制前請先配制澄清的儲備液，再依次添加助溶劑(為保證實驗結果的可靠性，體內實驗的作液，建議您現現配，當天使；澄清的儲備液可以根據儲存條件，適當保存；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: 2.08 mg/mL (2.62 mM); Clear solution2. 請依序添加每種溶劑： 10% DMSO 90% (20% SBE-CD in saline)Solubil

4、ity: 2.08 mg/mL (2.62 mM); Clear solution1/3 Master of Small Molecules 您邊的抑制劑師www.MedChemEBIOLOGICAL ACTIVITY物活性 Cenicriviroc Mesylate (TAK-652 Mesylate)種雙重 CCR2/CCR5 拮抗劑，同時可抑制 HIV-1 和 HIV-2，具有顯著的抗炎、抗感染的功效。IC50 & Target CCR5 CCR2 R5 HIV-1 R5 HIV-20.29 nM (IC50) 5.9 nM (IC50) 0.024-0.08 nM (IC50, 0.0

5、3-0.98 nM (IC50, inin PBMCs) PBMCs)體外研究 Migration of mouse monocytes in response to carbon tetrachloride (CCL2) is reduced following pre-treatmentwith Cenicriviroc Mesylate (CVC) at a concentration of 1 M. Compare to untreated and unstimulated cells,the average fold change in migrating cells (SD) is

6、 0.80.2 (p0.05) and 0.70.4 (p0.05) for CCL2-stimulated cells treated with Cenicriviroc Mesylate and unstimulated cells treated with Cenicriviroc Mesylate,respectively 1. Phenotypic susceptibility testing shows, for the four R5-tropic HIV-2 isolates, a median EC50for Cenicriviroc Mesylate of 0.39 nM

7、(0.03, 0.33, 0.45 and 0.98 nM). The dual-tropic and the X4-tropic HIV-2strains are resistant to Cenicriviroc Mesylate with EC50 at 1000 nM, and Maximum percentages of inhibition(MPI) at 33% and 4%, respectively 2.體內研究 Cenicriviroc Mesylate (CVC) treatment leads to dose-related decrease in monocyte/m

8、acrophage recruitment,and achieving statistical significance at doses 20 mg/kg/day (p 1.PROTOCOLCell Assay 1 Mouse monocyte migration in response to Cenicriviroc Mesylate (CVC) treatment is assessed ex vivo intriplicate. Thioglycollate (TG) is injected intraperitoneally into male C57BL/6 mice (n=3;

9、8 to 10 weeks of age)and activated macrophages are collected 48 hours later by peritoneal lavage. Cells are incubated for 2 hoursin the presence of 1 M Cenicriviroc Mesylate. Cells are harvested from the lower compartment andanalyzed by flow cytometry to enumerate F4/80+CD11b+ macrophages. Results a

10、re analyzed using FlowJosoftware 1.MCE has not independently confirmed the accuracy of these methods. They are for reference only.Animal Male C57BL/6 mice (n=44; 8 to 10 weeks of age) are allocated to receive treatments via oral gavage (PO) onAdministration 1 Days 1 to 5 in the following groups: non

11、-disease control, vehicle control twice daily (BID), CenicrivirocMesylate 5 mg/kg/day (CVC5) BID, Cenicriviroc Mesylate 20 mg/kg/day (CVC20) BID, Cenicriviroc Mesylate100 mg/kg/day (CVC100) BID, Cenicriviroc Mesylate 20 mg/kg once-daily (QD). On Day 4, peritonitis isinduced via IP injection of thiog

12、lycollate (TG) 3.85% (1 mL/animal) 2 hours post-dose in all groups exceptnon-disease controls 1.MCE has not independently confirmed the accuracy of these methods. They are for reference only.REFERENCES1. Lefebvre E, et al. Antifibrotic Effects of the Dual CCR2/CCR5 Antagonist Cenicriviroc in Animal

13、Models of Liver and Kidney Fibrosis.2/3 Master of Small Molecules 您邊的抑制劑師www.MedChemEPLoS One. 2016 Jun 27;11(6):e0158156.2. Visseaux B, et al. Cenicriviroc, a Novel CCR5 (R5) and CCR2 Antagonist, Shows In Vitro Activity against R5 Tropic HIV-2 ClinicalIsolates. PLoS One. 2015 Aug 6;10(8):e0134904.3

14、. Lalezari J, et al. Safety, efficacy, and pharmacokinetics of TBR-652, a CCR5/CCR2 antagonist, in HIV-1-infected, treatment-experienced, CCR5 antagonist-naive subjects. J Acquir Immune Defic Syndr. 2011 Jun 1;57(2):118-25.4. Baba M, et al. TAK-652 inhibits CCR5-mediated human immunodeficiency virus type 1 infection in vitro and has favorablepharmacokinetics in humans. Antimicrob Agents Chemother. 2005 Nov;4