Danoprevir (RG7227)
(Synonyms: 丹诺普韦; ITMN-191; R7227; RO5190591; RG7227) 目录号 : GC12879
An HCV NS3/4A protease inhibitor
Cas No.:850876-88-9
Sample solution is provided at 25 µL, 10mM.
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Quality Control & SDS
- View current batch:
- Purity: >99.50%
- COA (Certificate Of Analysis)
- SDS (Safety Data Sheet)
- Datasheet
| Kinase experiment [1]: | |
|
Binding assays |
Protease activity for K2040 and genotype 1 to 6 NS3 proteins was followed in a continuous fluorescent resonance energy transfer (FRET)-based assay. The assay buffer contained 25 μM NS4A peptide, 50 mM Tris-HCl, pH 7.5, 15% (vol/vol) glycerol, 0.6 mM lauryldimethylamine N-oxide, 10 mM dithiothreitol, and 0.5 μM fluorescein/QXL520-labeled FRET substrate. Typically, 50 pM K2040 enzyme was added to initiate the reaction. Reactions were set up in black 96-well plates, and fluorescence data were collected using a SpectraMax M5 plate reader. Recovery of activity from preformed ITMN-191·NS3/4A complex was assessed by preincubating 10 nM NS3/4A with a twofold excess of ITMN-191 in 1× assay buffer for 15 min, followed by a rapid 200-fold dilution of the preformed complex into assay buffer containing substrate. |
| Cell experiment [1]: | |
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Cell lines |
Huh7 cells harboring HCV replicon |
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Preparation method |
The solubility of this compound in DMSO is >32.6mg/mL. General tips for obtaining a higher concentration: Please warm the tube at 37 ℃ for 10 minutes and/or shake it in the ultrasonic bath for a while. Stock solution can be stored below -20℃ for several months. |
|
Reacting condition |
antiviral assays: 100 nM to 5 pMcytotoxicity assays: 1 mM to 5.6 nM |
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Applications |
ITMN-191 displayed a high degree of specificity for its intended target. In replicon-bearing cells, ITMN-191 (3.7 nM-15 nM) promoted a 3.7 log10 reduction in replicon levels upon 14 days of in vitro treatment but did not clear HCV replicon from every cell. Treatment with ITMN-191 (45 nM) reduced HCV replicon RNA levels and completely cleared replicon RNA. |
| Animal experiment [1]: | |
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Animal models |
Rats and monkeys |
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Dosage form |
Oral gavage, 30 mg/kg |
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Application |
Danoprevir (30 mg/kg) administered to rats or monkeys shows that its concentrations in liver 12 hours after dosing exceed the Danoprevir concentration required to eliminate replicon RNA from cells. |
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Other notes |
Please test the solubility of all compounds indoor, and the actual solubility may slightly differ with the theoretical value. This is caused by an experimental system error and it is normal. |
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References: [1]. Seiwert S D, Andrews S W, Jiang Y, et al. Preclinical characteristics of the hepatitis C virus NS3/4A protease inhibitor ITMN-191 (R7227)[J]. Antimicrobial agents and chemotherapy, 2008, 52(12): 4432-4441. |
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Danoprevir (R7227) is a potent and selective inhibitor of Hepatitis C Virus (HCV) NS3/4A protease, a chymotrypsin-like serine protease playing an essential role in the viral replication process of HCV, that non-covalently binds to and hence inhibits HCV NS3 protease with 50% inhibition concentration IC50 values ranging from 0.2 to 3.5 nM. X-ray crystallographic analysis has revealed that the cyclopropyl acylsulfonamide of danoprevir occupies the SI/SI’ pocket of HCV NS3 protease with the acyl carbonyl oxygen forming hydrogen bonds to Gly137 and Ser138 in the oxyanion hole of the protease active site and the acyl sulfonamide nitrogen forming a hydrogen bond with His57.
Reference
[1].Jiang Y, Andrews SW, Condroski KR, Buckman B, Serebryany V, Wenglowsky S, Kennedy AL, Madduru MR, Wang B, Lyon M, Doherty GA, Woodard BT, Lemieux C, Do MG, Zhang H, Ballard J, Vigers G, Brandhuber BJ, Stengel P, Josey JA, Beigelman L, Blatt L, Seiwert SD. Discovery of Danoprevir (ITMN-191/R7227), a Highly Selective and Potent Inhibitor of Hepatitis C Virus (HCV) NS3/4A Protease. J Med Chem. 2013 May 28. [Epub ahead of print]
| Cas No. | 850876-88-9 | SDF | |
| 别名 | 丹诺普韦; ITMN-191; R7227; RO5190591; RG7227 | ||
| 化学名 | (2R,6S,13aS,14aR,16aS,Z)-6-((tert-butoxycarbonyl)amino)-14a-((cyclopropylsulfonyl)carbamoyl)-5,16-dioxo-1,2,3,5,6,7,8,9,10,11,13a,14,14a,15,16,16a-hexadecahydrocyclopropa[e]pyrrolo[1,2-a][1,4]diazacyclopentadecin-2-yl 4-fluoroisoindoline-2-carboxylate | ||
| Canonical SMILES | FC1=CC=CC2=C1CN(C2)C(O[C@@H]3C[C@](C(N[C@@]4(C(NS(=O)(C5CC5)=O)=O)[C@@](/C=C\CCCCC[C@@H]6N([H])C(OC(C)(C)C)=O)([H])C4)=O)([H])N(C6=O)C3)=O | ||
| 分子式 | C35H46FN5O9S | 分子量 | 731.83 |
| 溶解度 | ≥ 32.6 mg/mL in DMSO, ≥ 46.4 mg/mL in EtOH with ultrasonic | 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 | 1.3664 mL | 6.8322 mL | 13.6644 mL |
| 5 mM | 0.2733 mL | 1.3664 mL | 2.7329 mL |
| 10 mM | 0.1366 mL | 0.6832 mL | 1.3664 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。