Nifeviroc
(Synonyms: 尼非韦罗) 目录号 : GC61879
Nifeviroc 是具有口服活性的 CCR5 拮抗剂。Nifeviroc 可用于 HIV-1 感染研究。
Cas No.:934740-33-7
Sample solution is provided at 25 µL, 10mM.
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Quality Control & SDS
- View current batch:
- Purity: >98.00%
- COA (Certificate Of Analysis)
- SDS (Safety Data Sheet)
- Datasheet
Nifeviroc is an orally active CCR5 antagonist. Nifeviroc is used for the study of HIV type-1 infection[1].
References:
[1]. Wei Wu, et al. Determination of nifeviroc, a novel CCR5 antagonist: application to a pharmacokinetic study. J Pharm Biomed Anal. 2011 Nov 1;56(3):637-40.
| Cas No. | 934740-33-7 | SDF | |
| 别名 | 尼非韦罗 | ||
| Canonical SMILES | O=C(OCC1=CC=C([N+]([O-])=O)C=C1)N(C2CCN(C[C@H]3CN(C(C4CCCC4)=O)C[C@]3(O)C5=CC=CC=C5)CC2)CC=C | ||
| 分子式 | C33H42N4O6 | 分子量 | 590.71 |
| 溶解度 | DMSO : 95 mg/mL (160.82 mM; Need ultrasonic); H2O : < 0.1 mg/mL (insoluble) | 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 | |||
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1 mg | 5 mg | 10 mg |
| 1 mM | 1.6929 mL | 8.4644 mL | 16.9288 mL |
| 5 mM | 0.3386 mL | 1.6929 mL | 3.3858 mL |
| 10 mM | 0.1693 mL | 0.8464 mL | 1.6929 mL |
| 第一步：请输入基本实验信息（考虑到实验过程中的损耗，建议多配一只动物的药量） | ||||||||||
| 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。
3. 以上所有助溶剂都可在 GlpBio 网站选购。
Determination of Nifeviroc, a novel CCR5 antagonist: application to a pharmacokinetic study
J Pharm Biomed Anal 2011 Nov 1;56(3):637-40.PMID:21802236DOI:10.1016/j.jpba.2011.06.027.
Nifeviroc is a novel CCR5 antagonist used for the treatment of HIV type-1 infection. A LC-ESI-MS/MS method for the determination of Nifeviroc in human plasma was developed and validated. The calibration curve (r(2)=0.9993) of Nifeviroc was established at the range of 1.924-2935 μg L(-1). The intra- and inter-day precisions (RSD%) were all less than 7%, and the accuracies at three concentration levels were all within 100 ± 5%. This validated method was then successfully applied to a pharmacokinetic study in health Chinese volunteers.
China's new drug R&D is steadily advancing
Drug Discov Ther 2007 Aug;1(1):3.PMID:22504356doi
China appears to consistently lag behind developed countries like the US, Japan, and the nations of Europe in the development of pharmaceuticals, putting China in an embarrassing situation. In fact, China is still dependent on foreign imports for most highly effective cures to major diseases such as cancer, diabetes, hepatitis, and neurodegenerative disease. There is no denying the fact that governmental support, and especially a signifi cant amount of fi nancial support and political assistance to include government restructuring, is needed for the establishment of new drug Research and Development (R&D). Fortunately, China's authorities have recently recognized the importance of new drug development and have committed to implementing strong measures to help establish new drug R&D. This improvement in the government's status is showing immediate and substantial promise in the field of pharmaceuticals. On January 4, 2007, a research group directed by Wang Ming-Wei, Head of the National Center for Drug Screening, Shanghai Institute of Materia Medica (SIMM), made a breakthrough in the development of novel category I anti-diabetes drugs with the support of the Ministry of Science & Technology of China, the National Natural Science Foundation (NSFC) of China, and the Shanghai municipal government. Taking almost four years, the group finally developed a nonpeptide agonist of small molecule glucagon-like peptide 1 receptors with effi cacy in diabetic db/db mice (Proc Natl Acad Sci U S A 2007;104:943-948). As an antidiabetes drug, a peptide hormone traditionally had to be taken as an injection, which greatly limited its clinical application. In contrast, the new compound can be taken orally. This offers hope for the development of a new field of peptidomimetics for orally-available nonpeptide small molecules. Today, the ever-growing prevalence of major diseases worldwide is driving growth in new drug spending, encouraging the marketing of newly developed and effi cacious therapies. This achievement appears to have significantly boosted the field of new drug research in China. While "China's pharmaceutical firms lag far behind [their Western counterparts] in terms of biological preparations" "today's achievement, with the attention it has garnered, has important scientific signifi cance and potential social and economic value," said Chen Zhu, the minister of health PRC and also the former associate dean of the China Academy of Sciences (http://www.simm.ac.cn/News/20071417649.htm , available as of January 4, 2007). Other encouraging news came from the Shanghai Life Sciences Institute. A novel anti-HIV compound named Nifeviroc was developed with the support of the municipal government and licensed for clinical trials on April 17, 2007 (Shanghai Daily, April 17, 2007). This is expected to become the world's first oral HIV entryinhibitor. Thus far, applications to patent Nifeviroc have been submitted in 14 countries and regions, including the United States, Japan, and the European Union. Recently, Shanghai Targetdrug Pharmaceutical Company and Avexa, a Melbourne-based drug-research company in Australian, announced that they will jointly develop Nifeviroc for global distribution. Avexa will handle post-research expenses, develop the drug in the international marketplace, and share global profits with Targetdrug. Thus, China may have justified rationale and confidence to believe that the day will come when China's pharmaceutical products will boast a strong presence in the global market.
Studies on the structure-activity relationship of 1,3,3,4-tetra-substituted pyrrolidine embodied CCR5 receptor antagonists. Part 1: Tuning the N-substituents
Bioorg Med Chem Lett 2010 Jul 15;20(14):4012-4.PMID:20561788DOI:10.1016/j.bmcl.2010.05.102.
A novel series of CCR5 antagonists has been identified, utilizing the lead, Nifeviroc, which were further modified based on bioisosteric principles. Lead optimization was pursued by balancing potential toxicity and potency. Potent analogues with low toxic properties were successfully developed by formation of urea and amide bonds at the nitrogen at position 4- of the pyrrolidine ring.
Identification of potential CCR5 inhibitors through pharmacophore-based virtual screening, molecular dynamics simulation and binding free energy analysis
Mol Biosyst 2016 Oct 18;12(11):3396-3406.PMID:27714030DOI:10.1039/c6mb00577b.
CC chemokine receptor 5 (CCR5), a member of G protein-coupled receptors (GPCRs), plays a vital role in inflammatory responses to infection. Alterations in the expression of CCR5 have been correlated with disease progression in many types of cancers. The idea of using CCR5 as a target for therapeutic intervention has been demonstrated to prevent disease progression. To date, only a few compounds have been reported as CCR5 inhibitors. In this study, a series of CCR5 antagonists were used to construct pharmacophore models. Then the optimal model was utilized as a 3D query to identify novel chemical entities from structural databases. After refinement by molecular docking, drug-likeness analysis, molecular dynamics simulations (MDS) and binding free energy analysis, three potential inhibitors (25, 29 and 45) were identified. MD simulations suggested that the screened compounds retained the important common binding mode known for CCR5 inhibitors (maraviroc and Nifeviroc), which occupied the bottom of a pocket and stabilized the conformation of CCR5. During the binding process, van der Waals interactions provided the substantial driving force. The most favorable contributions were from Tyr37, Trp86, Tyr89, Tyr108, Phe109, Phe112, Gln194, Thr195, Ile198, Trp248, Tyr251, Leu255, Thr259, Met279, Glu283 and Met287. The above results suggest that the hybrid strategy would provide a basis for rational drug design.