1. Anti-infection Metabolic Enzyme/Protease
  2. HCV Protease HCV SARS-CoV
  3. Danoprevir

Danoprevir  (Synonyms: 丹诺普韦; ITMN-191; R7227; RO5190591; RG7227)

目录号: HY-10238 纯度: 99.69%
COA 产品使用指南

Danoprevir (ITMN-191) 是一种具有口服活性的 NS3/4A蛋白酶抑制剂,IC50 值为 0.29 nM。与其他 53 种蛋白酶 (IC50高于 10 μM) 相比,对 NS3/4A 具有高选择性。Danoprevir (ITMN-191) 抑制 HCV 基因型 1a, 1b, 4, 5, 6 (IC50s=0.2-0.4 nM) 和 2b, 3a (IC50s=1.6, 3.5 nM)。Danoprevir 也是 SARS-CoV 3CLpro 的抑制剂,IC50 为 0.05 μM。

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Danoprevir Chemical Structure

Danoprevir Chemical Structure

CAS No. : 850876-88-9

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10 mM * 1 mL in DMSO ¥1932
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5 mg ¥1200
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10 mg ¥1900
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50 mg ¥6500
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Customer Review

    Danoprevir purchased from MCE. Usage Cited in: Virology. 2014 May;456-457:300-9.  [Abstract]

    Jurkat cells are transfected with plasmids expressing (A) HCV NS3/4A or (B) HPgV NS3/4AB-HA. Telaprevir, Boceprevir, and Danoprevir are added at concentrations of 100 µM, 16.6 µM, 2.7 µM, or 0 µM in 0.1% DMSO. Lysates are harvested after 24 h and resolved by immunoblots probed with anti-HCV NS3 (A) or anti-HA (B). The position of HCV NS3/4A (~75kDa), HCV NS3 (~73kDa), NS3/4AB-HA, and NS4B-HA (~30kDa) are indicated. Molecular markers are on the right.
    • 生物活性

    • 实验参考方法

    • 纯度 & 产品资料

    • 参考文献

    生物活性

    Danoprevir (ITMN-191) is an orally active NS3/4A protease inhibitor for hepatitis C virus (HCV) with an IC50 of 0.29 nM and is selective for NS3/4A over a panel of 53 proteases (IC50 higher than 10 μM). Danoprevir (ITMN-191) inhibits HCV genotypes 1a, 1b, 4, 5, and 6 (IC50s=0.2-0.4 nM) as well as 2b and 3a (IC50s=1.6, 3.5 nM)[1][2]. Danoprevir is also a SARS-CoV 3CLpro inhibitor with an IC50 of 0.05 μM[3].

    IC50 & Target

    IC50: 0.29 nM (NS3/4A protease), 0.2-3.5 nM (HCV genotypes 1a, 1b, 2b, 3a, 4, 5, 6)[2]

    体外研究
    (In Vitro)

    In Huh7.5 cells transfected with chimeric recombinant virus, Danoprevir (ITMN-191) shows antiviral inhibition effects against HCV genotypes 1, 4 and 6 with IC50 of 2-3 nM, which are >100-fold lower than genotypes 2/3/5 (280-750 nM)[1].
    Danoprevir (ITMN-191) inhibits the reference genotype 1 NS3/4A protease half-maximally, but a high dose of Danoprevir (ITMN-191) (10 μM) shows no appreciably inhibition in a panel of 79 proteases, ion channels, transporters, and cell surface receptors. Danoprevir (ITMN-191) remains bound to and inhibits NS3/4A for more than 5 hours after its initial association. Danoprevir (ITMN-191) (45 nM) eliminates a patient-derived HCV genotype 1b replicon from hepatocyte-derived Huh7 cells with an EC50 of 1.8 nM[2].
    In HCV subgenomic replicon cell lines containing the individual mutations, V36M, R109K, and V170A substitutions confer little or no resistance to Danoprevir (ITMN-191), but the R155K substitution confers a high level (62-fold increase) of resistance to Danoprevir[3].

    MCE has not independently confirmed the accuracy of these methods. They are for reference only.

    体内研究
    (In Vivo)

    Danoprevir (ITMN-191) (30 mg/kg, p.o.) 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[2].

    MCE has not independently confirmed the accuracy of these methods. They are for reference only.

    Clinical Trial
    分子量

    731.83

    Formula

    C35H46FN5O9S

    CAS 号
    性状

    固体

    颜色

    White to off-white

    中文名称

    丹诺普韦

    运输条件

    Room temperature in continental US; may vary elsewhere.

    储存方式
    Powder -20°C 3 years
    4°C 2 years
    In solvent -80°C 2 years
    -20°C 1 year
    溶解性数据
    细胞实验: 

    DMSO 中的溶解度 : ≥ 100 mg/mL (136.64 mM; 吸湿的 DMSO 对产品的溶解度有显著影响,请使用新开封的 DMSO)

    * "≥" means soluble, but saturation unknown.

    配制储备液
    浓度 溶剂体积 质量 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
    查看完整储备液配制表

    * 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, 2 years; -20°C, 1 year。-80°C储存时,请在2年内使用, -20°C储存时,请在1年内使用。

    • 摩尔计算器

    • 稀释计算器

    Mass (g) = Concentration (mol/L) × Volume (L) × Molecular Weight (g/mol)

    质量
    =
    浓度
    ×
    体积
    ×
    分子量 *

    Concentration (start) × Volume (start) = Concentration (final) × Volume (final)

    This equation is commonly abbreviated as: C1V1 = C2V2

    浓度 (start)

    C1

    ×
    体积 (start)

    V1

    =
    浓度 (final)

    C2

    ×
    体积 (final)

    V2

    动物实验:

    请根据您的 实验动物和给药方式 选择适当的溶解方案。

    以下溶解方案都请先按照 In Vitro 方式配制澄清的储备液,再依次添加助溶剂:
    ——为保证实验结果的可靠性,澄清的储备液可以根据储存条件,适当保存;体内实验的工作液,建议您现用现配,当天使用
    以下溶剂前显示的百分比是指该溶剂在您配制终溶液中的体积占比;如在配制过程中出现沉淀、析出现象,可以通过加热和/或超声的方式助溶

    • 方案 一

      请依序添加每种溶剂: 10% DMSO    40% PEG300    5% Tween-80    45% Saline

      Solubility: ≥ 2.5 mg/mL (3.42 mM); 澄清溶液

      此方案可获得 ≥ 2.5 mg/mL(饱和度未知)的澄清溶液。

      1 mL 工作液为例,取 100 μL 25.0 mg/mL 的澄清 DMSO 储备液加到 400 μL PEG300 中,混合均匀;再向上述体系中加入 50 μL Tween-80,混合均匀;然后再继续加入 450 μL 生理盐水 定容至 1 mL

      生理盐水的配制:将 0.9 g 氯化钠,溶解于 ddH₂O 并定容至 100 mL,可以得到澄清透明的生理盐水溶液。
    • 方案 二

      请依序添加每种溶剂: 10% DMSO    90% Corn Oil

      Solubility: ≥ 2.5 mg/mL (3.42 mM); 澄清溶液

      此方案可获得 ≥ 2.5 mg/mL(饱和度未知)的澄清溶液,此方案实验周期在半个月以上的动物实验酌情使用。

      1 mL 工作液为例,取 100 μL 25.0 mg/mL 的澄清 DMSO 储备液加到 900 μL玉米油中,混合均匀。

    动物溶解方案计算器
    请输入动物实验的基本信息:

    给药剂量

    mg/kg

    动物的平均体重

    g

    每只动物的给药体积

    μL

    动物数量

    由于实验过程有损耗,建议您多配一只动物的量
    请输入您的动物体内配方组成:
    %
    DMSO +
    +
    %
    Tween-80 +
    %
    Saline
    如果您的动物是免疫缺陷鼠或者体弱鼠,建议 DMSO 中的在最后工作液体系中的占比尽量不超过 2%。
    方案所需 助溶剂 包括:DMSO ,均可在 MCE 网站选购。 Tween 80,均可在 MCE 网站选购。
    计算结果
    工作液所需浓度 : mg/mL
    储备液配制方法 : mg 药物溶于 μL  DMSO(母液浓度为 mg/mL)。
    您所需的储备液浓度超过该产品的实测溶解度,以下方案仅供参考,如有需要,请与 MCE 中国技术支持联系。
    动物实验体内工作液的配制方法 : 取 μL DMSO 储备液,加入 μL  μL ,混合均匀至澄清,再加 μL Tween 80,混合均匀至澄清,再加 μL 生理盐水
    连续给药周期超过半月以上,请谨慎选择该方案。
    请确保第一步储备液溶解至澄清状态,从左到右依次添加助溶剂。您可采用超声加热 (超声清洗仪,建议频次 20-40 kHz),涡旋吹打等方式辅助溶解。
    纯度 & 产品资料

    纯度: 99.69%

    参考文献
    Kinase Assay
    [2]

    The assay buffer contains 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 {Ac-DE-Dap(QXL520)-EE-Abu-ψ-[COO]-AS-Cys(5-FAMsp)-NH2}. K2040 enzyme (50 pM) is added to initiate the reaction. Reactions are set up in black 96-well plates, and fluorescence data is collected. Control reactions lacking inhibitors and enzyme are included. Initial rates are calculated from the linear phase of the reaction (up to 1 hour) and are used to obtain IC50. Recovery of activity from preformed Danoprevir-NS3/4A complex is assessed by preincubating 10 nM NS3/4A with a two-fold excess of Danoprevir in 1× assay buffer for 15 min, followed by a rapid 200-fold dilution of the preformed complex into assay buffer containing substrate. A control reaction with the same final conditions without preincubation of NS3/4A and Danoprevir is initiated by the addition of enzyme to an otherwise-complete reaction mixture. Additional control reactions lack either Danoprevir or NS3. The progress of the reactions is followed over 5 hours.

    MCE has not independently confirmed the accuracy of these methods. They are for reference only.

    Animal Administration
    [2]

    Pharmacokinetic properties are evaluated in rats and monkeys. Sprague-Dawley rats (three per time point) are administered a 30-mg/kg of body weight dose of ITMN-191 by oral gavage (a 6-mg/mL solution in water). Cynomolgus monkeys (two per time point) are administered a 30-mg/kg dose of ITMN-191 by oral gavage (a 3-mg/mL solution in water). For each species, terminal blood samples and the entire perfused liver are collected 1, 4, 8, 12, and 24 h after dose administration. Blood samples are collected in EDTA, processed for plasma by centrifugation at 5°C, and stored at −20°C until analysis is performed. Liver samples are snap-frozen and stored at −70°C until analysis is performed. Blank, standard, and unknown plasma samples and homogenized liver containing an internal standard (ITMN-191 analog) are treated with acidified acetonitrile and centrifuged to remove precipitated proteins. The density of liver tissue is taken into account to allow concentrations in both compartments to be expressed as weight per unit volume. The cleared supernatants are diluted 1:1 into high-performance liquid chromatography grade water and analyzed on a 4000 Q-trap liquid chromatography-tandem mass spectrometer fitted with the Turbo-Ionspray source operating in negative-ion mode. Analytes and internal standards are monitored using multiple-reaction-monitoring scans and calibrated with ABI Analyst software, version 1.4.2. The calibration standards ranges from 0.0169 ng/mL to 37.0 ng/mL and from 7.47 ng/mL to 5,440 ng/mL for the quantification of plasma samples and liver homogenates, respectively. Quadratic fitting with 1/x weighting is utilized where an R2 value of > 0.999 is achieved in both matrices.

    MCE has not independently confirmed the accuracy of these methods. They are for reference only.

    参考文献

    完整储备液配制表

    * 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, 2 years; -20°C, 1 year。-80°C储存时,请在2年内使用, -20°C储存时,请在1年内使用。

    可选溶剂 浓度 溶剂体积 质量 1 mg 5 mg 10 mg 25 mg
    DMSO 1 mM 1.3664 mL 6.8322 mL 13.6644 mL 34.1609 mL
    5 mM 0.2733 mL 1.3664 mL 2.7329 mL 6.8322 mL
    10 mM 0.1366 mL 0.6832 mL 1.3664 mL 3.4161 mL
    15 mM 0.0911 mL 0.4555 mL 0.9110 mL 2.2774 mL
    20 mM 0.0683 mL 0.3416 mL 0.6832 mL 1.7080 mL
    25 mM 0.0547 mL 0.2733 mL 0.5466 mL 1.3664 mL
    30 mM 0.0455 mL 0.2277 mL 0.4555 mL 1.1387 mL
    40 mM 0.0342 mL 0.1708 mL 0.3416 mL 0.8540 mL
    50 mM 0.0273 mL 0.1366 mL 0.2733 mL 0.6832 mL
    60 mM 0.0228 mL 0.1139 mL 0.2277 mL 0.5693 mL
    80 mM 0.0171 mL 0.0854 mL 0.1708 mL 0.4270 mL
    100 mM 0.0137 mL 0.0683 mL 0.1366 mL 0.3416 mL
    Help & FAQs
    • Do most proteins show cross-species activity?

      Species cross-reactivity must be investigated individually for each product. Many human cytokines will produce a nice response in mouse cell lines, and many mouse proteins will show activity on human cells. Other proteins may have a lower specific activity when used in the opposite species.

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    产品名称:
    Danoprevir
    目录号:
    HY-10238
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