Danoprevir

製品コードS1183 バッチS118301

印刷

化学情報

Synonyms

ITMN-191, RG7227

Storage
(From the date of receipt)

3 years -20°C powder
1 years -80°C in solvent

化学式

C₃₅H₄₆FN₅O₉S

分子量

731.83

CAS No.

850876-88-9

Solubility (25°C)*

体外

DMSO

144 mg/mL (196.76 mM)

Ethanol

144 mg/mL (196.76 mM)

Water

Insoluble

体内（毎回新しく調製した物を用意してください）

Homogeneous suspension	CMC-NA	≥5mg/ml	Taking the 1 mL working solution as an example, add 5 mg of this product to 1 ml of CMC-Na solution, mix evenly to obtain a homogeneous suspension with a final concentration of 5 mg/ml.
Clear solution	5%DMSO 1 40%PEG300 2 5%Tween80 3 50%ddH2O この製剤はselleckのラボで検証済みです。上記の溶解方法がご要望を満たさない場合、selleckの営業担当までお問い合わせ頂ければ、個別の試験を行います。	3.600mg/ml (4.92mM)	Taking the 1 mL working solution as an example, add 50 μL of 72 mg/ml clarified DMSO stock solution to 400 μL of PEG300, mix evenly to clarify it; add 50 μL of Tween80 to the above system, mix evenly to clarify; then continue to add 500 μL of ddH2O to adjust the volume to 1 mL. The mixed solution should be used immediately for optimal results.
Clear solution	5% DMSO 1 95% Corn oil この製剤はselleckのラボで検証済みです。上記の溶解方法がご要望を満たさない場合、selleckの営業担当までお問い合わせ頂ければ、個別の試験を行います。	1.210mg/ml (1.65mM)	Taking the 1 mL working solution as an example, add 50 μL of 24.2 mg/ml clear DMSO stock solution to 950 μL of corn oil and mix evenly. The mixed solution should be used immediately for optimal results.

* <1 mg/ml means slightly soluble or insoluble.
* Please note that Selleck tests the solubility of all compounds in-house, and the actual solubility may differ slightly from published values. This is normal and is due to slight batch-to-batch variations.

溶剤液（一定の濃度）を調合する

生物活性

製品説明	ダノプレビルは、C型肝炎ウイルス (HCV) のNS3/4A プロテアーゼのペプチドミメティック阻害剤であり、IC50は0.2-3.5 nMです。HCVジェノタイプ1A/1B/4/5/6に対する阻害効果は、2B/3Aより約10倍高くなっています。第2相。
in vitro	Danoprevir (0.29 nM) inhibits the reference genotype 1 NS3/4A protease half-maximally, but a high dose of this compound (10 μM) shows no appreciably inhibition in a panel of 79 proteases, ion channels, transporters, and cell surface receptors. It remains bound to and inhibits NS3/4A for more than 5 hours after its initial association. This chemical (45 nM) eliminates a patient-derived HCV genotype 1b replicon from hepatocyte-derived Huh7 cells with an EC50 of 1.8 nM. In HCV subgenomic replicon cell lines containing the individual mutations, V36M, R109K, and V170A substitutions confer little or no resistance to it, but the R155K substitution confers a high level (62-fold increase) of resistance to this compound. In Huh7.5 cells transfected with chimeric recombinant virus, it 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).
in vivo	Danoprevir (30 mg/kg) administered to rats or monkeys shows that its concentrations in liver 12 hours after dosing exceed the concentration of this compound required to eliminate replicon RNA from cells.
特徴	A peptidomimetic inhibitor of the NS3/4A protease of hepatitis C virus (HCV).

プロトコル(参考用のみ)

キナーゼアッセイ	Continuous fluorescent resonance energy transfer (FRET) assay
キナーゼアッセイ	The assay buffer contains 25 μM NS4A peptide, 50 mM Tris-HCl, pH 7.5, 15% vol/vol, 10 mM dithiothreitol, and 0.5 μM 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 this compound-NS3/4A complex is assessed by preincubating 10 nM NS3/4A with a two-fold excess of this chemical 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 this compound is initiated by the addition of enzyme to an otherwise-complete reaction mixture. Additional control reactions lack either this chemical or NS3. The progress of the reactions is followed over 5 hours.
細胞アッセイ	細胞株	Huh7 cells harboring HCV replicon
	濃度	5 pM - 100 nM
	反応時間	48 hours
	実験の流れ	Serially diluted Danoprevir is added to Huh7 cells harboring the K2040 replicon 1 day after cell plating. For antiviral assays, after a 48-hour incubation, intracellular RNA is extracted, and the level of HCV replicon RNA is quantified by reverse transcription (RT)-PCR assay with the primers (5'-CACTCCCCTGTGAGGAACTACTG-3' and 5'-AGGCTGCACGACACTCATACT-3') and a probe (5'-6-FAM-CTTCACGCAGAAAGCGTCTAGCCATGG-MGBNFQ-3' using an ABI Prism 7900 sequence detection system. Here, FAM is 6-carboxyfluorescin and MGBNFQ is a molecular-groove binding non-fluorescence quencher specific to the HCV 5' untranslated region. Single-tube reactions are performed using the TaqMan Gold RT-PCR kit. Triplicate reactions for the RNA standards and samples are performed in 50 μL with 5 μL intracellular RNA (50 ng). RT is carried out at 48 °C for 30 min followed by 10 min at 95 °C. The PCR is run as follows: 15 seconds at 95 °C and 1 min at 60 °C for 40 cycles. Each RNA concentration is determined in triplicate. The absolute concentration of replicon RNA is calculated based on its signal relative to that of a standard curve generated by known concentrations of an in vitro-transcribed RNA corresponding to a genotype 1b 5' untranslated region. Replicon levels in the presence of this compound are fitted to a four-parameter logistic function to obtain EC50.
動物実験	動物モデル	Sprague-Dawley rats, Cynomolgus monkeys
	投薬量	30 mg/kg
	投与方法	Oral gavage

参考

https://pubmed.ncbi.nlm.nih.gov/18824605/
https://pubmed.ncbi.nlm.nih.gov/18637752/
https://pubmed.ncbi.nlm.nih.gov/21480315/

カスタマーフィードバック

: Data from [Data independently produced by Mol Biol Evol, 2014, 31(6), 1546-53]

: Data from [Data independently produced by Antimicrob Agents Chemother, 2012, 56(10), 5365-73]

: Data from [PLoS One, 2012, 7, e42481]

Selleckの高級品が、幾つかの出版された研究調査結果（以下を含む）で使われた：

Targeting eEF1A reprograms translation and uncovers broad-spectrum antivirals against cap or m6A protein synthesis routes [ Nat Commun, 2025, 16(1):1087]	PubMed: 39920115
The exon junction complex coordinates the cotranscriptional inclusion of blocks of neighboring exons [ Genes Dev, 2025, 10.1101/gad.353081.125]	PubMed: 41102016
Zbtb16 determines the fate plasticity of cardiovascular progenitors through IGF2BP3-mediated mRNA stabilization [ Cell Rep, 2025, 44(8):116127]	PubMed: 40779394
Small Molecule Targeting of Atypical p38 Protects Against Viral Infection [ FASEB J, 2025, 39(20):e71096]	PubMed: 41082179
Preclinical characterization of a non-peptidomimetic HIV protease inhibitor with improved metabolic stability [ Antimicrob Agents Chemother, 2024, 68(4):e0137323.]	PubMed: 38380945
Mechanisms of Action of the Host-Targeting Agent Cyclosporin A and Direct-Acting Antiviral Agents against Hepatitis C Virus [ Viruses, 2023, 15(4)981]	PubMed: 37112961
RECOVER identifies synergistic drug combinations in vitro through sequential model optimization [ Cell Rep Methods, 2023, 3(10):100599]	PubMed: 37797618
Integrative multiomics and in silico analysis revealed the role of ARHGEF1 and its screened antagonist in mild and severe COVID-19 patients [ J Cell Biochem, 2022, 10.1002/jcb.30213]	PubMed: 35037717
Hepatitis C virus drugs that inhibit SARS-CoV-2 papain-like protease synergize with remdesivir to suppress viral replication in cell culture [ Cell Rep, 2021, 35(7):109133]	PubMed: 33984267
Characterization of fluorescent probe substrates to develop an efficient high-throughput assay for neonatal hepatic CYP3A7 inhibition screening [ Sci Rep, 2021, 11(1):19443]	PubMed: 34593846

長期の保管のために-20°Cの下で製品を保ってください。

人間や獣医の診断であるか治療的な使用のためにでない。

各々の製品のための特定の保管と取扱い情報は、製品データシートの上で示されます。大部分のSelleck製品は、推薦された状況の下で安定です。製品は、推薦された保管温度と異なる温度で、時々出荷されます。長期の保管のために必要とされてそれと異なる温度で、多くの製品は、短期もので安定です。品質を維持するが、夜通しの積荷のために最も経済的な貯蔵状況を用いてあなたの送料を保存する状況の下に、製品が出荷されることを、我々は確実とします。製品の受領と同時に、製品データシートの上で貯蔵推薦に従ってください。