Cenicriviroc
(Synonyms: TAK-652; TBR-652) 目录号 : GC19101
Cenicriviroc (CVC) 是一种口服的 CCR2/CCR5 双重拮抗剂，对这两种受体具有纳摩尔效力。
Cas No.:497223-25-3
Sample solution is provided at 25 µL, 10mM.
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Cenicriviroc (CVC) is an oral, dual CCR2/CCR5 antagonist with nanomolar potency against both receptors[1].
Cenicriviroc is a small-molecule chemokine receptor antagonist with highly potent and selective anti-human immunodeficiency virus type 1 (HIV-1) activity through antagonizing CCR5 as a coreceptor of HIV-1. Cenicriviroc also strongly antagonizes CCR2b, thereby it has potent anti-inflammatory and immunomodulatory effects[2].
Cenicriviroc is a selective inhibitor of SARS-CoV-2 replication.When VeroE6/TMPRSS2 cells were infected with SARS-CoV-2 and incubated in the absence of compounds for 3 days, the cells were completely destroyed by the virus-induced cytopathic effect (Fig. 1 B). Such cell destruction was not observed for the infected cells in the presence of 20 μM Cenicriviroc, although some morphological changes were identified[3].
Repeated intrathecal injections of Cenicriviroc in a dose-dependent manner alleviated neuropathic pain-related behaviors in rats after sciatic nerve injury. Cenicriviroc decreased the activation and/or infiltration of IBA-1-positive cells (microglia/macrophages) in the spinal cord and DRG, and satellite cells in the DRG, and likely as a consequence reduced the level of some important pronociceptive factors (IL-1beta, IL-6, IL-18, and CCL3). Importantly, from a clinical perspective, cenicriviroc enhanced the analgesic potency of morphine and buprenorphine. These beneficial behavioral effects may result, among others, from the influence of cenicriviroc on the mRNA level of opioid receptors (MOR, DOR, KOR, and NOR) at the DRG level. Our results provide the first evidence that simultaneous targeting of CCR2 and CCR5 using cenicriviroc may have great potential for use in neuropathic pain therapies, especially since it is already under clinical trials, though in other health concerns[3].
References:
[1]. Lefebvre E, Moyle G, 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].Okamoto M, Toyama M, et al. The chemokine receptor antagonist cenicriviroc inhibits the replication of SARS-CoV-2 in vitro. Antiviral Res. 2020 Oct;182:104902.
[3].Kwiatkowski K, Pawlik K, et al. Bidirectional Action of Cenicriviroc, a CCR2/CCR5 Antagonist, Results in Alleviation of Pain-Related Behaviors and Potentiation of Opioid Analgesia in Rats With Peripheral Neuropathy. Front Immunol. 2020 Dec 21;11:615327.
Cenicriviroc (CVC) 是一种口服的 CCR2/CCR5 双重拮抗剂，对这两种受体具有纳摩尔效力[1]。
Cenicriviroc 是一种小分子趋化因子受体拮抗剂，通过拮抗作为 HIV-1 辅助受体的 CCR5，具有高效和选择性的抗人类免疫缺陷病毒 1 型 (HIV-1) 活性。 Cenicriviroc 还强烈拮抗 CCR2b，因此具有有效的抗炎和免疫调节作用[2]。
Cenicriviroc 是 SARS-CoV-2 复制的选择性抑制剂。当 VeroE6/TMPRSS2 细胞感染 SARS-CoV-2 并在没有化合物的情况下孵育 3 天时，细胞被病毒诱导的完全破坏细胞病变效应（图 1 B）。在 20 μM Cenicriviroc 存在的情况下，没有观察到受感染细胞的这种细胞破坏，尽管发现了一些形态学变化[3]。
以剂量依赖性方式重复鞘内注射 Cenicriviroc 可减轻坐骨神经损伤后大鼠的神经性疼痛相关行为。 Cenicriviroc 降低了脊髓和 DRG 中 IBA-1 阳性细胞（小胶质细胞/巨噬细胞）以及 DRG 中卫星细胞的激活和/或浸润，并可能因此降低了一些重要的伤害感受因子（IL- 1beta、IL-6、IL-18 和 CCL3）。重要的是，从临床角度来看，cenicriviroc 增强了吗啡和丁丙诺啡的镇痛效力。除其他外，这些有益的行为影响可能是由于 cenicriviroc 对 DRG 水平的阿片受体（MOR、DOR、KOR 和 NOR）mRNA 水平的影响。我们的结果提供了第一个证据，表明使用 cenicriviroc 同时靶向 CCR2 和 CCR5 可能具有用于神经性疼痛治疗的巨大潜力，特别是因为它已经在进行临床试验，尽管在其他健康问题上[3] .
| Cell experiment [1]: | |
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Cell lines |
human hepatocyte cell line(Huh7.5,Huh7.5JFH1) |
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Preparation Method |
Huh7.5JFH1 cells were plated in 24-well format. After 24 hours, cells were incubated with cenicriviroc.The chemokines MIP-1 alpha MIP-1 beta, and RANTES/CCL5 were quantified in cell supernatants at day 1 and day 3 after addition of Cenicriviroc. |
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Reaction Conditions |
Hepatocyte cell line were treated with Cenicriviroc (0.0025, 0.25, 25 ug/mL) for 24 h. |
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Applications |
HCV core protein levels were significantly reduced in the presence of 0.25 and 25 ug/mL of cenicriviroc.MIP-1 beta expression at day 1 was somewhat lower in the presence of cenicriviroc compared to the no-drug control condition. |
| Animal experiment [2]: | |
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Animal models |
C57BL/6 mice |
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Preparation Method |
Cenicriviroc was administered by oral gavage on Days 1–5. On Day 4, peritonitis was induced via IP injection of TG 3.85% (1 mL/animal) 2 hours post-dose. |
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Dosage form |
5,20,100mg/kg/day, oral gavage |
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Applications |
In vivo mouse model of peritonitis In the TG-induced model of peritonitis, Cenicriviroc treatment led to dose-related decreases in monocyte/macrophage recruitment, of similar or greater magnitude than those observed with dexamethasone.The most potent mediator of chemotaxis for activated macrophages, was reduced following pretreatment with Cenicriviroc at a concentration of 1μM. |
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References: [1]. Blackard JT, Kong L, et al. CCR5 receptor antagonism inhibits hepatitis C virus (HCV) replication in vitro. PLoS One. 2019 Oct 29;14(10):e0224523. [2]. Lefebvre E, Moyle G, 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. |
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| Cas No. | 497223-25-3 | SDF | |
| 别名 | TAK-652; TBR-652 | ||
| 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 | ||
| 分子式 | C41H52N4O4S | 分子量 | 696.94 |
| 溶解度 | DMSO : ≥ 107.5 mg/mL (135.55 mM) | 储存条件 | Store at -20°C |
| General tips | 请根据产品在不同溶剂中的溶解度选择合适的溶剂配制储备液；一旦配成溶液，请分装保存，避免反复冻融造成的产品失效。 储备液的保存方式和期限：-80°C 储存时，请在 6 个月内使用，-20°C 储存时，请在 1 个月内使用。 为了提高溶解度，请将管子加热至37℃，然后在超声波浴中震荡一段时间。 |
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| Shipping Condition | 评估样品解决方案：配备蓝冰进行发货。所有其他可用尺寸：配备RT，或根据请求配备蓝冰。 | ||
| 制备储备液 | |||
 |
1 mg | 5 mg | 10 mg |
| 1 mM | 1.4348 mL | 7.1742 mL | 14.3484 mL |
| 5 mM | 0.287 mL | 1.4348 mL | 2.8697 mL |
| 10 mM | 0.1435 mL | 0.7174 mL | 1.4348 mL |
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| 给药剂量 | mg/kg |  |
动物平均体重 | g | |
每只动物给药体积 | ul | |
动物数量 | 只 |
| 第二步：请输入动物体内配方组成（配方适用于不溶于水的药物；不同批次药物配方比例不同，请联系GLPBIO为您提供正确的澄清溶液配方） | ||||||||||
| % DMSO % % Tween 80 % saline | ||||||||||
| 计算重置 | ||||||||||
计算结果:
工作液浓度： mg/ml；
DMSO母液配制方法： mg 药物溶于 μL DMSO溶液（母液浓度 mg/mL，
体内配方配制方法：取 μL DMSO母液，加入 μL PEG300，混匀澄清后加入μL Tween 80，混匀澄清后加入 μL saline，混匀澄清。
1. 首先保证母液是澄清的；
2.
一定要按照顺序依次将溶剂加入，进行下一步操作之前必须保证上一步操作得到的是澄清的溶液，可采用涡旋、超声或水浴加热等物理方法助溶。
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Quality Control & SDS
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- Purity: >98.00%
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