Boceprevir
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.
Boceprevir是一种有效的和选择性的丙型肝炎病毒(HCV)蛋白酶NS3抑制剂,Ki值为14 nM[1]。
丙型肝炎病毒是一种RNA病毒,感染全球约3亿人。作为HCV的丝氨酸蛋白酶,NS3在病毒进入宿主细胞后HCV的复制过程中具有重要作用。NS3可加工由病毒RNA基因组翻译而来的多聚蛋白,促进病毒的成熟。NS3也可以恢复干扰素敏感的信号通路。由于这些特点,NS3被认为是抗病毒治疗的适当靶标。SAR研究导致boceprevir(SCH 503034)的发现。Boceprevir有一个酮酰胺基,其与NS3结合形成一个共价的和可逆的加合物,具有丝氨酸活性位点[1,2和3]。
在用肝细胞所做的基于细胞的复制子实验中,boceprevir比其它衍生物具有更高的效力,IC90值为350 nM。Boceprevir的选择性通过与人嗜中性细胞弹性蛋白酶的结合而测定,其与NS3具有相似的结构。Boceprevir具有很大的选择性,HNE/HCV的比例为2200。Boceprevir比相应的氨基甲酸酯衍生物具有近15倍的选择性。在MTS实验中,该化合物在浓度高达50 μM时没有显著的细胞毒性效应[1]。
Boceprevir是一种可口服的HCV NS3蛋白酶抑制剂。在大鼠中,boceprevir口服给药具有1.5 μMH的AUC值和26%的生物利用度。在狗中,boceprevir以3 mg/kg的剂量给药具有30%的生物利用度和3.1 μMH的AUC值。Boceprevir也可与聚乙二醇干扰素(PEG-IFN-α-2B)用作联合疗法,与单独每个相比较,其联合治疗至少具有累积的效力[1,2]。
参考文献:
1. Venkatraman S, Bogen S L, Arasappan A, et al. Discovery of (1 R, 5 S)-N-[3-Amino-1-(cyclobutylmethyl)-2, 3-dioxopropyl]-3-[2 (S)-[[[(1, 1-dimethylethyl) amino] carbonyl] amino]-3, 3-dimethyl-1-oxobutyl]-6, 6-dimethyl-3-azabicyclo [3.1. 0] hexan-2 (S)-carboxamide (SCH 503034), a Selective, Potent, Orally Bioavailable Hepatitis C Virus NS3 Protease Inhibitor: A Potential Therapeutic Agent for the Treatment of Hepatitis C Infection. Journal of medicinal chemistry, 2006, 49(20): 6074-6086.
2. Sarrazin C, Rouzier R, Wagner F, et al. SCH 503034, a novel hepatitis C virus protease inhibitor, plus pegylated interferon α-2b for genotype 1 nonresponders. Gastroenterology, 2007, 132(4): 1270-1278.
3. Flores M V, Strawbridge J, Ciaramella G, et al. HCV-NS3 inhibitors: determination of their kinetic parameters and mechanism. Biochimica et Biophysica Acta (BBA)-Proteins and Proteomics, 2009, 1794(10): 1441-1448.
Physical Appearance | A solid |
Storage | Store at -20°C |
M.Wt | 519.68 |
Cas No. | 394730-60-0 |
Formula | C27H45N5O5 |
Synonyms | Boceprevir ,EBP 520;SCH 503034;EBP-520;EBP520;SCH-503034;SCH503034 |
Solubility | ≥25.98 mg/mL in DMSO; insoluble in H2O; ≥89.8 mg/mL in EtOH |
Chemical Name | (1R,2S,5S)-N-(4-amino-1-cyclobutyl-3,4-dioxobutan-2-yl)-3-[(2S)-2-(tert-butylcarbamoylamino)-3,3-dimethylbutanoyl]-6,6-dimethyl-3-azabicyclo[3.1.0]hexane-2-carboxamide |
SDF | Download SDF |
Canonical SMILES | CC1(C2C1C(N(C2)C(=O)C(C(C)(C)C)NC(=O)NC(C)(C)C)C(=O)NC(CC3CCC3)C(=O)C(=O)N)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。 |
Cell experiment:[1] | |
Cell lines |
HuH-7 cells |
Reaction Conditions |
For 72 h incubation |
Applications |
The EC50 and EC90 values of boceprevir on HuH-7 cells bearing the subgenomic hepatitis C virus (HCV) replicon were determined to be 0.20 µM and 0.35 µM, respectively. |
Animal experiment:[2] | |
Animal models |
NS3/4A/Lap/LC-1 triple-transgenic mice induced with doxycycline |
Dosage form |
100 mg/kg Twice daily by oral gavage for 7 days |
Applications |
Oral administration of boceprevir led to a 65% reduction in the average plasma Gaussia luciferase (Gluc) activity. Notably, Gluc activity gradually reverted back to the pre-treatment level when boceprevir treatment ceased. |
Note |
The technical data provided above is for reference only. |
References: 1. Njoroge FG, Chen KX, Shih NY, et al. Challenges in modern drug discovery: a case study of boceprevir, an HCV protease inhibitor for the treatment of hepatitis C virus infection. Accounts of Chemical Research, 2008, 41(1): 50-59. 2. Yao M, Lu X, Lei Y, et al. Conditional Inducible Triple-Transgenic Mouse Model for Rapid Real-Time Detection of HCV NS3/4A Protease Activity. PLoS One, 2016, 11(3): e0150894. |
Description | Boceprevir(EBP-520, SCH503034)是HCV蛋白酶的抑制剂,Ki值为14 nM。 | |||||
靶点 | HCV protease | |||||
IC50 | 14 nM (Ki) |
质量控制和MSDS
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