- MK-5172 potassium salt
- MK-5172
- Simeprevir
- MK-5172 sodium salt
- MK-5172 hydrate
- Asunaprevir (BMS-650032)
| Danoprevir (RG7227)HCV NS3/4A protease inhibitor |
Sample solution is provided at 25 µL, 10mM.
Nature.2017 Jan 19;541(7637):417-420.
Nature.2018 Nov;563(7731):407-411.Nature.2018 Jun 13.Nature.2018 Jun 27.Nature.2018 Mar 29;555(7698):673-677.Nature.2017 Sep 7;549(7670):96-100.Nature.2016 Apr 21;532(7599):398-401.
Science.2016 Aug 5;353(6299)594-8Nat Nanotechnol.2017 Dec;12(12):1190-1198.Nature Biotechnology.2017 Jun;35(6):569-576Nat Med.2018 Sep 17.Cell.2018 Dec 21. pii: S0092-8674(18)31561-7.Cell.Available online 25 October 2018.Cell.2018 Sep 27. pii: S0092-8674(18)31183-8.Cell.2018 Jun 28;174(1):172-186.e21.Cell.2018 Feb 22;172(5):1007-1021.e17.Cell.2017 Nov 30;171(6):1284-1300.e21.Cell.2017 Aug 17. pii: S0092-8674(17)30869-3.Cell.2017 Jul 13;170(2):312-323Nat Med.2018 Jan 29.Nat Med.2017 Nov;23(11):1342-1351.Cell.2017 Apr 6;169(2):286-300.Cell.2015 Aug 27;162(5):987-1002.Cell.2015 Feb 12;160(4):729-44.Nature Medicine.2017 Apr;23(4):493-500.Cancer Cell.2018 May 14;33(5):905-921.e5.Cancer Cell.2018 Apr 9;33(4):752-769.e8.Cancer Cell.2018 Mar 12;33(3):401-416.e8.Cancer Cell.2017 Aug 14;32(2):253-267.e5.Nat Methods.2018 Jul;15(7):523-526.Cell Stem Cell.2018 May 3;22(5):769-778.e4.Cell Stem Cell.2017 Nov 20. pii: S1934-5909(17)30375-2.Quality Control & MSDS
- View current batch:
- Purity = 98.09%
- COA (Certificate Of Analysis)
- HPLC
- NMR (Nuclear Magnetic Resonance)
- MSDS (Material Safety Data Sheet)
- Datasheet
Chemical structure
| Description | Danoprevir is a highly selective and potent inhibitor of HCV NS3/4A protease with IC50 value of 0.2-3.5 nM. | |||||
| Targets | HCV NS3/4A protease | |||||
| IC50 | 0.2-3.5 nM | |||||
| Kinase experiment [1]: | |
Binding assays | Protease activity for K2040 and genotype 1 to 6 NS3 proteins was followed in a continuous fluorescent resonance energy transfer (FRET)-based assay. The assay buffer contained 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. Typically, 50 pM K2040 enzyme was added to initiate the reaction. Reactions were set up in black 96-well plates, and fluorescence data were collected using a SpectraMax M5 plate reader. Recovery of activity from preformed ITMN-191·NS3/4A complex was assessed by preincubating 10 nM NS3/4A with a twofold excess of ITMN-191 in 1× assay buffer for 15 min, followed by a rapid 200-fold dilution of the preformed complex into assay buffer containing substrate. |
| Cell experiment [1]: | |
Cell lines | Huh7 cells harboring HCV replicon |
Preparation method | The solubility of this compound in DMSO is >32.6mg/mL. General tips for obtaining a higher concentration: Please warm the tube at 37 ℃ for 10 minutes and/or shake it in the ultrasonic bath for a while. Stock solution can be stored below -20℃ for several months. |
Reacting condition | antiviral assays: 100 nM to 5 pMcytotoxicity assays: 1 mM to 5.6 nM |
Applications | ITMN-191 displayed a high degree of specificity for its intended target. In replicon-bearing cells, ITMN-191 (3.7 nM-15 nM) promoted a 3.7 log10 reduction in replicon levels upon 14 days of in vitro treatment but did not clear HCV replicon from every cell. Treatment with ITMN-191 (45 nM) reduced HCV replicon RNA levels and completely cleared replicon RNA. |
| Animal experiment [1]: | |
Animal models | Rats and monkeys |
Dosage form | Oral gavage, 30 mg/kg |
Application | Danoprevir (30 mg/kg) 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. |
Other notes | Please test the solubility of all compounds indoor, and the actual solubility may slightly differ with the theoretical value. This is caused by an experimental system error and it is normal. |
References: [1]. Seiwert S D, Andrews S W, Jiang Y, et al. Preclinical characteristics of the hepatitis C virus NS3/4A protease inhibitor ITMN-191 (R7227)[J]. Antimicrobial agents and chemotherapy, 2008, 52(12): 4432-4441. | |
Danoprevir (RG7227) Dilution Calculator
calculate
Danoprevir (RG7227) Molarity Calculator
calculate
| Cas No. | 850876-88-9 | SDF | Download SDF |
| Synonyms | Danoprevir,RG7227,ITMN-191 | ||
| Chemical Name | (2R,6S,13aS,14aR,16aS,Z)-6-((tert-butoxycarbonyl)amino)-14a-((cyclopropylsulfonyl)carbamoyl)-5,16-dioxo-1,2,3,5,6,7,8,9,10,11,13a,14,14a,15,16,16a-hexadecahydrocyclopropa[e]pyrrolo[1,2-a][1,4]diazacyclopentadecin-2-yl 4-fluoroisoindoline-2-carboxylate | ||
| Canonical SMILES | FC1=CC=CC2=C1CN(C2)C(O[C@@H]3C[C@](C(N[C@@]4(C(NS(=O)(C5CC5)=O)=O)[C@@](/C=CCCCCC[C@@H]6N([H])C(OC(C)(C)C)=O)([H])C4)=O)([H])N(C6=O)C3)=O | ||
| Formula | C35H46FN5O9S | M.Wt | 731.83 |
| Solubility | ≥32.6 mg/mL in DMSO, ≥46.4 mg/mL in EtOH with ultrasonic, <2.26 mg/ml="" in="" h2o=""> | Storage | Store at -20°C |
| Physical Appearance | A solid | Shipping Condition | Evaluation sample solution : ship with blue ice.All other available size:ship with RT , or blue ice upon request |
| General tips | For obtaining a higher solubility , please warm the tube at 37 ℃ and shake it in the ultrasonic bath for a while.Stock solution can be stored below -20℃ for several months. | ||
Danoprevir (R7227) is a potent and selective inhibitor of Hepatitis C Virus (HCV) NS3/4A protease, a chymotrypsin-like serine protease playing an essential role in the viral replication process of HCV, that non-covalently binds to and hence inhibits HCV NS3 protease with 50% inhibition concentration IC50 values ranging from 0.2 to 3.5 nM. X-ray crystallographic analysis has revealed that the cyclopropyl acylsulfonamide of danoprevir occupies the SI/SI’ pocket of HCV NS3 protease with the acyl carbonyl oxygen forming hydrogen bonds to Gly137 and Ser138 in the oxyanion hole of the protease active site and the acyl sulfonamide nitrogen forming a hydrogen bond with His57.
Reference
Jiang Y, Andrews SW, Condroski KR, Buckman B, Serebryany V, Wenglowsky S, Kennedy AL, Madduru MR, Wang B, Lyon M, Doherty GA, Woodard BT, Lemieux C, Do MG, Zhang H, Ballard J, Vigers G, Brandhuber BJ, Stengel P, Josey JA, Beigelman L, Blatt L, Seiwert SD. Discovery of Danoprevir (ITMN-191/R7227), a Highly Selective and Potent Inhibitor of Hepatitis C Virus (HCV) NS3/4A Protease. J Med Chem. 2013 May 28. [Epub ahead of print]
ebiomall.com
>
>
>
>
>
>
>
>
>
>
>
PH酸度计仪器的级别0.2级0.1级0.02级0.01级0.001级
分度值或最小显示值(pH)0.20.10.020.010.001
电计示值误差(pH)±0.1±0.05±0.01±0.01±0.002
配套测试示值总误差(pH)±0.2±0.1±0.02±0.02±0.01
注：配套测试时的测试范围应控制在pH3～pH10内。从上表可以看出，对于0.01级以下的酸度计，示值总误差数值等于其级别，对于0.01级的酸度计，示值总误差为0.02pH，对于0.001级酸度计，其示值总误差也只能达到±0.01pH，而且此时需要使用一级pH标准物质才能得到保证。(注意：pH国家标准物质分一级和二级两种，一般酸度计常用的是二级pH标准物质。)向左转|向右转
玻璃电极在初次使用前，必须在蒸馏水中浸泡一昼夜以上。
平时也应浸泡在蒸馏水中以备随时使用。玻璃电极不要与强吸水溶剂接触太久，在强碱溶液中使用应尽快操作，用毕立即用水洗净，玻璃电极球泡膜很薄，不能与玻璃杯及硬物相碰；玻璃膜沾上油污时，应先用酒精，再用四氯化碳或乙醚，最后用酒精浸泡，再用蒸馏水洗净。注意电极内要充满氯化钾溶液，应无气泡，防止断路。应有少许氯化钾结晶存在，以使溶液保持饱和状态，使用时拨去电极上顶端的橡皮塞，从毛细管中流出少量的氯化钾溶液，使测定结果可靠。
另外，pH测定的准确性取决于标准缓冲液的准确性。酸度计用的标准缓冲液，要求有较大的稳定性，较小的温度依赖性。
测定时把复合电极插在被测溶液中，由于被测溶液的酸度（氢离子浓度）不同而产生不同的电动势，将它通过直流放大器放大，最后由读数指示器（电压表）指出被测溶液的pH值。酸度计能在0～14pH值范围内使用。酸度计有台式、便携式、表型式等多种，读数指示器有数字式和指针式两种.
1、校正：先将仪器斜率调节器调节在100％位置，再根据被测溶液的温度，调节温度调节器到该温度值。
2、定位：把复合电极插入仪器，选择一种最接近样品pH值的缓冲溶液，把电极放入这一缓冲溶液里，摇动烧杯，使溶液均匀.待读数稳定后，该读数应是缓冲溶液的pH值，否则就要调节定位调节器。用于分析精度要求较高的测定时，要选择两种缓冲溶液（即被测样品的pH值在该两种缓冲溶液的pH值之间或接近）。待第种缓冲溶液的pH值读数稳定后，该读数应为该缓冲溶液的pH值，否则调节定位调节器。清洗电极，吸干电极球泡表面的余液。把电极放入第二种缓冲溶液中，摇动烧杯使溶液均匀，待读数稳定后，该读数应是第二种缓冲溶液的pH值，否则调节斜率调节器。
3、测量：经过pH标定的仪器，即可用来测定样品的pH值。这时温度调节器、定位调节器、斜率调节器都不能再动，用蒸馏水清洗电极，用滤纸吸干电极球部后。把电极插在盛有被测样品的烧杯内，轻轻摇动烧杯，待读数稳定后，就显示被测样品的pH值。复合电极的主要传感部分是电极的球泡，球泡极薄，千万不能跟硬物接触。测量完毕套上保护帽，帽内放少量补充液（3mol/L的氯化钾溶液），保持电极球泡湿润.仪器采用CMOS集成电路，不用时插入短路插头。检修时电烙铁要有良好的接地，以保护仪器。
按测量精度
可分0.2级、0.1级、0.01级或更高精度。
按仪器体积
分为笔式（迷你型）、便携式、台式还有在线连续监控测量的在线式。
根据使用的要求
笔式（迷你型）与便携式pH酸碱度计一般是检测人员带到现场检测使用。
选择pH酸碱度计的精度级别是根据用户测量所需的精度决定，而后根据用户方便使用而选择各式形状的pH计。
◆按便携性分的，分为：便携式pH计，台式pH计和笔式pH计。
◆按用途分为：实验室用pH计，工业在线pH计等。
◆按先进程度分为经济型pH计，智能型pH计，精密型pH计或分为指针式pH计，数显式pH计。
◆笔式pH计，一般制成单一量程，测量范围狭，为专用简便仪器。
便携式和台式pH计测量范围较广，常用仪器，不同点是便携式采用直流供电，可携带到现场。实验室pH计测量范围广、功能多、测量精度高。
工业用pH计的特点是要求稳定性好、工作可靠，有一定的测量精度、环境适应能力强、抗干扰能力强，具有模拟里量输出、数字通讯、上下限报警和控制功能等。向左转|向右转
现代酸度计具有：结构简单，操作方便，测量准确和自动化程度高的优点。
