- 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. | |
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| 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]
