Narlaprevir
mRNA synthesis
In vitro transcription of capped mRNA with modified nucleotides and Poly(A) tail
Tyramide Signal Amplification (TSA)
TSA (Tyramide Signal Amplification), used for signal amplification of ISH, IHC and IC etc.
Phos Binding Reagent Acrylamide
Separation of phosphorylated and non-phosphorylated proteins without phospho-specific antibody
Cell Counting Kit-8 (CCK-8)
A convenient and sensitive way for cell proliferation assay and cytotoxicity assay
SYBR Safe DNA Gel Stain
Safe and sensitive stain for visualization of DNA or RNA in agarose or acrylamide gels.
Inhibitor Cocktails
Protect the integrity of proteins from multiple proteases and phosphatases for different applications.
Narlaprevir是HCV NS3蛋白酶强有力的第二代抑制剂,Ki值为6 nM [1]。
丙型肝炎病毒感染是一个全球性的公共卫生问题,它甚至可以导致肝硬化和肝癌。NS3是HCV复制所必需的酶,NS3丝氨酸蛋白酶被认为是用于治疗HCV感染的重要靶标。Narlaprevir是NS3蛋白酶的抑制剂之一。不同于boceprevir,narlaprevir是单一同种型,具有明显改善的效能。在抑制NS3蛋白酶的过程中,narlaprevir首先非共价结合在酶上,然后利用可逆共价键结合活性位点Ser139 [1,2, 3]。
在体外测定中,narlaprevir抑制基因型为1a、1b、2a和3a的NS3蛋白酶,Ki值分别为0.7、7、3和7 nM。在病毒复制子抑制测定中,narlaprevir表现出明显的抗病毒效力,EC50和EC90值分别为20和40 nM。除此之外,narlaprevir对宿主细胞没有细胞毒性。Narlaprevir可以与聚乙二醇干扰素组成联合疗法。与 narlaprevir的单一疗法相比,narlaprevir和干扰素α-2b的组合治疗显著提高了对复制子的抑制活性[2]。
在动物实验中,narlaprevir改善了AUC和生物利用度的药代动力学。在大鼠、猴和狗中,AUC的药代动力学分别为6.5 μM?h、1.1 μM?h和0.9 μM?h。 Narlaprevir在三种动物中的生物利用度分别为46%、46%和29%[1]。
一些抗药性突变A156T(EC50=1 μM)、T54A(EC50=11 nM)和双突变(T54A和A156T)需要高浓度narlaprevir。 还发现,narlaprevir对boceprevir耐药性的突变,如V170A、F43C和V36M(EC50=8 nM)具有交叉耐药性[2,3]。
参考文献:
1. Arasappan A, Bennett F, Bogen S L, et al. Discovery of narlaprevir (SCH 900518): a potent, second generation HCV NS3 serine protease inhibitor. ACS Medicinal Chemistry Letters, 2010, 1(2): 64-69.
2.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. Antimicrobial agents and chemotherapy, 2010, 54(6): 2365-2370.
3.Wang H, Geng L, Chen B Z, et al. Computational study on the molecular mechanisms of drug resistance of Narlaprevir due to V36M, R155K, V36M+ R155K, T54A, and A156T mutations of HCV NS3/4A protease. Biochemistry and Cell Biology, 2014, 92(5): 357-369.
Storage | Store at -20°C |
M.Wt | 707.96 |
Cas No. | 865466-24-6 |
Formula | C36H61N5O7S |
Synonyms | SCH 900518;SCH900518;SCH-900518 |
Solubility | Soluble in DMSO |
Chemical Name | (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 |
SDF | Download SDF |
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 |
运输条件 | 蓝冰运输或根据您的需求运输。 |
一般建议 | 不同厂家不同批次产品溶解度各有差异,仅做参考。若实验所需浓度过大至产品溶解极限,请添加助溶剂助溶或自行调整浓度。溶液形式一般不宜长期储存,请尽快用完。 |
描述 | Narlaprevir是一个有效的、选择性的和具有口服生物学效应的NS3蛋白酶抑制剂,Ki和EC90值分别与6 nM和40 nM。 | |||||
靶点 | NS3 protease | |||||
IC50 | (Ki=6 nM; EC90=40 nM) |