Cenicriviroc Mesylate (Synonyms: TAK-652 Mesylate; TBR-652 Mesylate) |
カタログ番号GC35650
One-Click Copy Product Info
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セニクリビロック メシル酸塩 (TAK-652 メシル酸塩) は、デュアル CCR2/CCR5 アンタゴニストであり、HIV-1 と HIV-2 の両方を阻害し、強力な抗炎症および抗感染活性を示します。
Products are for research use only. Not for human use. We do not sell to patients.
Cas No.: 497223-28-6
Sample solution is provided at 25 µL, 10mM.
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Cenicriviroc Mesylate (TAK-652 Mesylate) is a dual CCR2/CCR5 antagonist, also inhibits both HIV-1 and HIV-2, and displays potent anti-inflammatory and antiinfective activity. CCR5|0.29 nM (IC50)|CCR2|5.9 nM (IC50)|R5 HIV-1|0.024-0.08 nM (IC50, in PBMCs)|R5 HIV-2|0.03-0.98 nM (IC50, in PBMCs)
Migration of mouse monocytes in response to carbon tetrachloride (CCL2) is reduced following pre-treatment with Cenicriviroc Mesylate (CVC) at a concentration of 1 μM. Compare to untreated and unstimulated cells, the average fold change in migrating cells (±SD) is 0.8±0.2 (p>0.05) and 0.7±0.4 (p>0.05) 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 EC50 for Cenicriviroc Mesylate of 0.39 nM (0.03, 0.33, 0.45 and 0.98 nM). The dual-tropic and the X4-tropic HIV-2 strains are resistant to Cenicriviroc Mesylate with EC50 at >1000 nM, and Maximum percentages of inhibition (MPI) at 33% and 4%, respectively[2].
Cenicriviroc Mesylate (CVC) treatment leads to dose-related decrease in monocyte/macrophage recruitment, and achieving statistical significance at doses ≥20 mg/kg/day (p<0.05). Compare to the vehicle-control group, peritoneal lavage monocyte/macrophage counts are decreased by: 5.7%, 45.2%, 76.5% and 26.0% for Cenicriviroc Mesylate 5 twice daily (BID), Cenicriviroc Mesylate20 twice daily (BID), Cenicriviroc Mesylate100 BID, Cenicriviroc Mesylate 20 once-daily (QD), respectively. Exposure to Cenicriviroc Mesylate is dose-related and correlated with the decrease in monocyte/macrophage recruitment, with Cenicriviroc Mesylate appearing to be more effective when given BID versus QD, in line with the higher plasma concentrations achieved with BID dosing and the known short half-life in mice (~2 hours)[1].
[1]. Lefebvre E, et al. Antifibrotic Effects of the Dual CCR2/CCR5 Antagonist Cenicriviroc in Animal Models of Liver and Kidney Fibrosis. PLoS 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 Clinical Isolates. PLoS One. 2015 Aug 6;10(8):e0134904. [3]. 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 favorable pharmacokinetics in humans. Antimicrob Agents Chemother. 2005 Nov;49(11):4584-91.
Cell experiment: | Mouse monocyte migration in response to Cenicriviroc Mesylate (CVC) treatment is assessed ex vivo in triplicate. Thioglycollate (TG) is injected intraperitoneally into male C57BL/6 mice (n=3; 8 to 10 weeks of age) and activated macrophages are collected 48 hours later by peritoneal lavage. Cells are incubated for 2 hours in the presence of 1 μM Cenicriviroc Mesylate. Cells are harvested from the lower compartment and analyzed by flow cytometry to enumerate F4/80+CD11b+ macrophages. Results are analyzed using FlowJo software[1]. |
Animal experiment: | Male C57BL/6 mice (n=44; 8 to 10 weeks of age) are allocated to receive treatments via oral gavage (PO) on Days 1 to 5 in the following groups: non-disease control, vehicle control twice daily (BID), Cenicriviroc Mesylate 5 mg/kg/day (CVC5) BID, Cenicriviroc Mesylate 20 mg/kg/day (CVC20) BID, Cenicriviroc Mesylate 100 mg/kg/day (CVC100) BID, Cenicriviroc Mesylate 20 mg/kg once-daily (QD). On Day 4, peritonitis is induced via IP injection of thioglycollate (TG) 3.85% (1 mL/animal) 2 hours post-dose in all groups except non-disease controls[1]. |
References: [1]. Lefebvre E, et al. Antifibrotic Effects of the Dual CCR2/CCR5 Antagonist Cenicriviroc in Animal Models of Liver and Kidney Fibrosis. PLoS One. 2016 Jun 27;11(6):e0158156. | |
| Cas No. | 497223-28-6 | SDF | |
| 同義語 | TAK-652 Mesylate; TBR-652 Mesylate | ||
| Canonical SMILES | O=C(/C1=C/C2=CC(C3=CC=C(OCCOCCCC)C=C3)=CC=C2N(CC(C)C)CCC1)NC4=CC=C([S@](CC5=CN=CN5CCC)=O)C=C4.OS(=O)(C)=O | ||
| Formula | C42H56N4O7S2 | M.Wt | 793.05 |
| 溶解度 | DMSO: 100 mg/mL (126.10 mM) | 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 | 1.261 mL | 6.3048 mL | 12.6095 mL |
| 5 mM | 252.2 μL | 1.261 mL | 2.5219 mL |
| 10 mM | 126.1 μL | 630.5 μL | 1.261 mL |
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Quality Control & SDS
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- Purity: >98.50% Appearance: A solid
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Average Rating: 5 (Based on Reviews and 6 reference(s) in Google Scholar.)