| Size | Price | Stock | Qty |
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| 5mg |
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| 10mg |
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| 25mg |
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| 50mg |
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| 100mg |
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| 250mg |
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Purity: ≥98%
Simeprevir sodium, the sodium salt of simeprevir (previously known as TMC43), is a competitive, reversible, macrocyclic, noncovalent inhibitor of the hepatitis C virus (HCV) NS3/4A protease. It acts directly against the hepatitis C virus and has been approved by the US FDA for use in combination with peginterferon-alfa and ribavirin to treat hepatitis C and hepatitis B. Simeprevir has also received approval in Japan for the treatment of chronic hepatitis C infection, genotype 1. It has a medium inhibitory concentration with IC50<13 nM for all HCV NS3/4A enzymes (genotypes 1a, 1b, 2, 4, 5, and 6), but has an IC50 value of 37 nM for genotype 3.
| Targets |
HCV NS3/4A protease(Ki=0.36 nM);HCV replication(EC50=7.8 nM);SARS-CoV-2 Mpro(IC50=9.6±2.3 μM);SARS-CoV-2 RdRp(IC50=5.5±0.2 μM)
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| ln Vitro |
the antiviral activity of simeprevir (TMC435350) in Huh7-Luc cells is dose dependent, and the EC50 and EC90 values determined for TMC435350 are 8 nM and 24 nM, respectively. Inhibition of TMC435350 on NS3/4A protease is time dependent, and the overall Kis are estimated to be 0.5 nM for genotype 1a and 0.4 nM for genotype 1b, respectively. TMC435350 is a potent inhibitor of HCV NS3/4A protease (Ki=0.36 nM) and viral replication (replicon EC50=7.8 nM).
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| ln Vivo |
In rats, TMC435350 (40 mg/kg, p.o.) is extensively distributed to the liver and intestinal tract (tissue/plasma area under the concentration-time curve ratios of >35), and the absolute bioavailability is 44%.
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| Enzyme Assay |
the in vitro inhibitory activity of simeprevir against NS3/4A is determined using a fluorescence resonance energy transfer cleavage assay with the RetS1 peptide substrate, derived from the genotype 1a NS4A-4B junction, and bacterially expressed full-length NS3 protease domain, supplemented with an NS4A peptide. Briefly, NS3/4A is preincubated in the presence of TMC435350 for 10 min, and then the RetS1 substrate is added and fluorescence is continuously measured for 20 min (excitation, 355 nm; emission, 500 nm). Cleavage of the substrate is expressed as a percentage of the cleavage seen with the vehicle control.
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| Cell Assay |
Huh7-Luc cells are seeded at a density of 2,500 cells/well in a 384-well plate in Dulbeccos modified Eagles medium plus 10% fetal calf serum and incubated with a range of concentrations of serially diluted simeprevir (TMC435350), in a final DMSO concentration of 0.5% in the absence of G418. After 72 h of incubation, Steady Lite reagent is added in a 1:1 ratio to the medium, and luciferase signal is measured using a ViewLux reader.
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| Animal Protocol |
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| References | |||
| Additional Infomation |
See also: Simeprevir (has active moiety).
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| Molecular Formula |
C38H46N5O7NAS2
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|---|---|
| Molecular Weight |
771.92
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| Exact Mass |
771.274
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| Elemental Analysis |
C, 59.13; H, 6.01; N, 9.07; Na, 2.98; O, 14.51; S, 8.31
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| CAS # |
1241946-89-3
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| Related CAS # |
Simeprevir;923604-59-5
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| PubChem CID |
46866715
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| Appearance |
Solid powder
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| LogP |
7.227
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| Hydrogen Bond Donor Count |
1
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| Hydrogen Bond Acceptor Count |
11
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| Rotatable Bond Count |
8
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| Heavy Atom Count |
53
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| Complexity |
1490
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| Defined Atom Stereocenter Count |
5
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| SMILES |
S(C1CC1)([N-]C([C@@]12CC1C=CCCCCN(C)C([C@@H]1C[C@@H](C[C@H]1C(N2)=O)OC1C=C(C2=NC(C(C)C)=CS2)N=C2C(C)=C(C=CC=12)OC)=O)=O)(=O)=O.[Na+] |c:11|
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| InChi Key |
LLXQGDWGCCKOQP-MVZLLIIPSA-M
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| InChi Code |
InChI=1S/C38H47N5O7S2.Na/c1-21(2)30-20-51-35(40-30)29-18-32(26-13-14-31(49-5)22(3)33(26)39-29)50-24-16-27-28(17-24)36(45)43(4)15-9-7-6-8-10-23-19-38(23,41-34(27)44)37(46)42-52(47,48)25-11-12-25;/h8,10,13-14,18,20-21,23-25,27-28H,6-7,9,11-12,15-17,19H2,1-5H3,(H2,41,42,44,46);/q;+1/p-1/b10-8-;/t23-,24-,27-,28-,38-;/m1./s1
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| Chemical Name |
sodium (cyclopropylsulfonyl)((2R,3aR,11aS,12aR,14aR,Z)-2-((2-(4-isopropylthiazol-2-yl)-7-methoxy-8-methylquinolin-4-yl)oxy)-5-methyl-4,14-dioxo-1,2,3,3a,4,5,6,7,8,9,11a,12,12a,13,14,14a-hexadecahydrocyclopenta[c]cyclopropa[g][1,6]diazacyclotetradecine-12a-carbonyl)amide
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| Synonyms |
TMC435; TMC 435; TMC435; Simeprevir; Olysio.
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| HS Tariff Code |
2934.99.9001
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| Storage |
Powder -20°C 3 years 4°C 2 years In solvent -80°C 6 months -20°C 1 month |
| Shipping Condition |
Room temperature (This product is stable at ambient temperature for a few days during ordinary shipping and time spent in Customs)
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| Solubility (In Vitro) |
DMSO : 14.29~100 mg/mL ( 19.05 ~133.34 mM )
Ethanol : ~4 mg/mL |
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| Solubility (In Vivo) |
5% DMSO+40% PEG300+5% Tween-80+50% Saline: 2.5 mg/mL (3.33 mM) (Please use freshly prepared in vivo formulations for optimal results.)
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| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 1.2955 mL | 6.4774 mL | 12.9547 mL | |
| 5 mM | 0.2591 mL | 1.2955 mL | 2.5909 mL | |
| 10 mM | 0.1295 mL | 0.6477 mL | 1.2955 mL |
*Note: Please select an appropriate solvent for the preparation of stock solution based on your experiment needs. For most products, DMSO can be used for preparing stock solutions (e.g. 5 mM, 10 mM, or 20 mM concentration); some products with high aqueous solubility may be dissolved in water directly. Solubility information is available at the above Solubility Data section. Once the stock solution is prepared, aliquot it to routine usage volumes and store at -20°C or -80°C. Avoid repeated freeze and thaw cycles.
Calculation results
Working concentration： mg/mL；
Method for preparing DMSO stock solution： mg drug pre-dissolved in μL DMSO (stock solution concentration mg/mL). Please contact us first if the concentration exceeds the DMSO solubility of the batch of drug.
Method for preparing in vivo formulation:：Take μL DMSO stock solution, next add μL PEG300, mix and clarify, next addμL Tween 80, mix and clarify, next add μL ddH2O，mix and clarify.
(1) Please be sure that the solution is clear before the addition of next solvent. Dissolution methods like vortex, ultrasound or warming and heat may be used to aid dissolving.
(2) Be sure to add the solvent(s) in order.
Inhibition of HCV replication in genotype 1b replicon cells treated with TMC435350.Antimicrob Agents Chemother.2009 Apr;53(4):1377-85. |
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Mutual influence between TMC435350 and IFN-α as analyzed by the Loewe additivity model.Antimicrob Agents Chemother.2009 Apr;53(4):1377-85. |
Nine-day incubation of genotype 1b replicon cells with TMC435350 alone, IFN-α alone, and TMC435350 in combination with IFN-α.Antimicrob Agents Chemother.2009 Apr;53(4):1377-85. |
Tissue distribution of TMC435350 after a single oral administration of 40 mg/kg in Sprague-Dawley rats.Antimicrob Agents Chemother.2009 Apr;53(4):1377-85. |
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Time-dependent exposure after single oral administration of 40 mg/kg TMC435350 in plasma and liver tissue of Sprague-Dawley rats.Antimicrob Agents Chemother.2009 Apr;53(4):1377-85. |
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