Narlaprevir是一种具有高效选择性和口服活性的丙型肝炎病毒的非结构蛋白3（HCV NS3）抑制剂，Ki值为6nM，EC90值为40nM。
Cas No.:865466-24-6
Sample solution is provided at 25 µL, 10mM.
_1-3.$$$39978408@51.jpg');)
_1-9.$$$38538795@65.jpg');)
_1-9.$$$39112701@51.jpg');)
_1-7.$$$37316672@70.jpg');)
_366-372.$$$36198801@70.jpg');)
.$$$38565142@65.jpg');)
_1867-1883.$$$33248023@67.jpg');)
_eads6055.$$$39977546@45.jpg');)
_eadm9805.$$$40080571@45.jpg');)
_eadj3020.$$$39666821@45.jpg');)
_1-20.$$$39757301@28.jpg');)
_1-24.$$$38898113@28.jpg');)
_273-287.$$$36806353@46.jpg');)
_1-16.$$$37156877@44.jpg');)
_1-19.$$$37460805@44.jpg');)
_1291-1307.$$$34518654@46.jpg');)
Narlaprevir is a highly selective and orally active inhibitor of the hepatitis C virus non-structural protein 3 (HCV NS3), with a Ki value of 6nM and an EC90 value of 40nM[1]. HCV NS3 plays a critical role in viral replication and possesses both protease and helicase functions[2]. Narlaprevir inhibits viral replication in host cells by forming a reversible covalent bond with the active site of the HCV NS3 protease, and is commonly used in the treatment and research of chronic HCV infection[3,4,5].
In vitro, treatment of HCV genotype 1b subgenomic replicon Huh-7 cells with Narlaprevir (EC50 = 20nM, EC90 = 40nM) for 72h significantly inhibited HCV RNA replication[6].
In vivo, Narlaprevir (10mg/kg) was administered orally to rats, with a bioavailability of 46% and a liver concentration of 750ng/g 8h after administration[1].
References:
[1] ARASAPPAN A, BENNETT F, BOGEN S L, et al. Discovery of narlaprevir (SCH 900518): a potent, second generation HCV NS3 serine protease inhibitor[J]. ACS Medicinal Chemistry Letters, 2010, 1(2): 64-69.
[2] ZHOU T, REN X, ADAMS R L, et al. NS3 from hepatitis C virus strain JFH-1 is an unusually robust helicase that is primed to bind and unwind viral RNA[J]. Journal of Virology, 2018, 92(1): e01253-17.
[3] BAI Y, YE F, FENG Y, et al. Structural basis for the inhibition of the SARS-CoV-2 main protease by the anti-HCV drug narlaprevir[J]. Signal Transduction and Targeted Therapy, 2021, 6(1): 51.
[4] ISAKOV V, KOLODA D, TIKHONOVA N, et al. Pharmacokinetics of the new hepatitis C virus NS3 protease inhibitor narlaprevir following single-dose use with or without ritonavir in patients with liver cirrhosis[J]. Antimicrobial Agents and Chemotherapy, 2016, 60(12): 7098-7104.
[5] MARTINO S D, PETRI G L, DE ROSA M. Hepatitis C: the story of a long journey through first, second, and third generation NS3/4A peptidomimetic inhibitors. What did we learn?[J]. Journal of Medicinal Chemistry, 2024, 67(2): 885-921.
[6] TONG X, ARASAPPAN A, BENNETT F, et al. Preclinical characterization of the antiviral activity of SCH 900518 (narlaprevir), a novel mechanism-based inhibitor of hepatitis C virus NS3 protease[J]. Antimicrobial Agents and Chemotherapy, 2010, 54(6): 2365-2370.
Narlaprevir是一种具有高效选择性和口服活性的丙型肝炎病毒的非结构蛋白3（HCV NS3）抑制剂，Ki值为6nM，EC90值为40nM[1]。HCV NS3在病毒复制中起关键作用，具有蛋白酶和解螺旋双重功能[2]。Narlaprevir通过与HCV的NS3蛋白酶活性位点进行可逆共价结合，抑制病毒在宿主细胞内的复制，通常用于慢性HCV的治疗和研究[3,4,5]。
在体外，Narlaprevir（EC50 = 20nM, EC90 = 40nM）处理HCV基因1b型亚基因组复制子Huh-7细胞72h，显著抑制了HCV RNA复制[6]。
在体内，Narlaprevir（10mg/kg）通过口服给药于大鼠，生物利用度为46%，给药后8h肝脏内浓度为750ng/g[1]。
| Cell experiment [1]: | |
Cell lines | HCV replicon Huh-7 cells |
Preparation Method | Replicon cells were treated with Narlaprevir for 3 days, and replicon RNA levels were measured by TaqMan assay. The average (with SD) of the relative reduction in the replicon RNA level (dCT) from triplicate measurements was plotted against the log compound concentration. |
Reaction Conditions | 72h |
Applications | The EC50 and EC90 values for Narlaprevir were 20 ± 6nM and 40 ± 10nM, respectively, in a 72h assay. |
| Animal experiment [2]: | |
Animal models | Rat (strain and sex not specified) |
Preparation Method | Rats were given a single 10mg/kg oral dose of Narlaprevir. Blood samples were collected for pharmacokinetic analysis. |
Dosage form | 10mg/kg; p.o. |
Applications | A single oral dose of Narlaprevir (10mg/kg) demonstrated a bioavailability of 46% in rats, with a liver concentration of 750ng/g at 8h post-dose. |
References: | |
| Cas No. | 865466-24-6 | SDF | |
| 别名 | 那拉匹韦; SCH 900518 | ||
| 化学名 | (1R,2S,5S)-3-[(2S)-2-[[1-(tert-butylsulfonylmethyl)cyclohexyl]carbamoylamino]-3,3-dimethylbutanoyl]-N-[(3S)-1-(cyclopropylamino)-1,2-dioxoheptan-3-yl]-6,6-dimethyl-3-azabicyclo[3.1.0]hexane-2-carboxamide | ||
| Canonical SMILES | CCCCC(C(=O)C(=O)NC1CC1)NC(=O)C2C3C(C3(C)C)CN2C(=O)C(C(C)(C)C)NC(=O)NC4(CCCCC4)CS(=O)(=O)C(C)(C)C | ||
| 分子式 | C36H61N5O7S | 分子量 | 707.96 |
| 溶解度 | DMSO : ≥ 50 mg/mL (70.63 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。 |
||
| 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 | 1.4125 mL | 7.0625 mL | 14.1251 mL |
| 5 mM | 282.5 μL | 1.4125 mL | 2.825 mL |
| 10 mM | 141.3 μL | 706.3 μL | 1.4125 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。
Quality Control & SDS
- View current batch:
- Purity: >98.00% Appearance: A solid
- COA (Certificate of Analysis)
- SDS (Safety Data Sheet)
- Datasheet