1. Anti-infection
    Metabolic Enzyme/Protease
  2. HCV
    HCV Protease

Simeprevir (Synonyms: TMC435)

Cat. No.: HY-10241 Purity: 99.34%
Handling Instructions

Simeprevir is a potent HCV NS3/4A protease inhibitor, and inhibits HCV replication with EC50 of 8 nM.

For research use only. We do not sell to patients.

Simeprevir Chemical Structure

Simeprevir Chemical Structure

CAS No. : 923604-59-5

Size Price Stock Quantity
Free Sample (0.5-1 mg)   Apply now  
10 mM * 1 mL in DMSO USD 238 In-stock
Estimated Time of Arrival: December 31
5 mg USD 144 In-stock
Estimated Time of Arrival: December 31
10 mg USD 252 In-stock
Estimated Time of Arrival: December 31
50 mg USD 1068 In-stock
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100 mg USD 1800 In-stock
Estimated Time of Arrival: December 31
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    Simeprevir purchased from MCE. Usage Cited in: Int J Radiat Oncol Biol Phys. 2016 Nov 15;96(4):867-876.

    Simeprevir inhibits DNA damage repair following irradiation. U251, BT474, and HepG2 cells are pretreated with Simeprevir or DMSO and irradiated at a dose of 6 Gy. After 6 hours, prolongation of γH2AX foci is detected in Simeprevir-treated cells along with decreased phosphorylation of DNA-PKcs, indicating impaired nonhomologous end-joining repair.

    Simeprevir purchased from MCE. Usage Cited in: J Med Chem. 2016 Nov 23;59(22):10268-10284.

    Huh7.5 cells are infected with HCV (45 IU/cell) and simultaneously treated with Simeprevir (A, 0.025 μM), Sofosbuvir (B, 0.1 μM), or Daclatasvir (C, 16 pM) alone or with 1 (6.25 μM).

    Simeprevir purchased from MCE. Usage Cited in: Biomed Res Int. 2017;2017:1236801.

    Huh7.5 (HCV+) cells are treated with 1 μM of Simeprevir or solvent control. At 24 hours, the cells are washed and continuously incubated with fresh culture media containing drugs again for 48 hours. The cultural supernatants are then harvested and directly incubated to naïve Huh7.5 cells. After been passaged 1~3 times, the newly infected cells are treated with 1 μM of Simeprevir for 72 hours. Intracellular proteins are extracted and detected with WB.

    Simeprevir purchased from MCE. Usage Cited in: Biomed Res Int. 2017;2017:1236801.

    Huh7.5 (HCV+) cells are treated with 1 μM of Sofosbuvir or solvent control. At 24 hours, the cells are washed and continuously incubated with fresh culture media containing drugs again for 48 hours. The cultural supernatants are then harvested and directly incubated to naïve Huh7.5 cells. After been passaged 1~3 times, the newly infected cells are treated with 1 μM of Sofosbuvir for 72 hours. Intracellular proteins are extracted and detected with WB.

    Simeprevir purchased from MCE. Usage Cited in: Biomed Res Int. 2017;2017:1236801.

    Naïve Huh7.5 cells are infected with wild and mutant type HCV and simultaneously treated with drugs. Intracellular proteins were extracted and detected with WB in 72 hours. Telaprevir (VX-950) against WT and A156T mutant HCV.

    Simeprevir purchased from MCE. Usage Cited in: Eur J Med Chem. 2018 Jan 1;143:1053-1065.

    GS4.3 cells are treated with 7f (20 μM), or Telaprevir (0.5μM), Sofosbuvir (0.8 μM), Daclatasvir (0.15 μM) or solvent control for 6 days.

    Simeprevir purchased from MCE. Usage Cited in: Eur J Med Chem. 2018 Jan 1;143:1053-1065.

    Huh7.5 cells are infected with HCV and simultaneously treated with 7f (10 μM) or DAA (0.04 μM Simeprevir, 0.08 μM Sofosbuvir, or 16 pM Daclatasvir) or 7f plus DAA.
    • Biological Activity

    • Protocol

    • Technical Information

    • Purity & Documentation

    • References

    Description

    Simeprevir is a potent HCV NS3/4A protease inhibitor, and inhibits HCV replication with EC50 of 8 nM.

    IC50 & Target

    EC50: 8 nM

    In Vitro

    In Huh7-Luc cells, antiviral activity of simeprevir (TMC435350) 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[1]. TMC435350 is a potent inhibitor of HCV NS3/4A protease (Ki=0.36 nM) and viral replication (replicon EC50=7.8 nM)[2].

    In 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%[1].

    Clinical Trial
    Solvent & Solubility
    In Vitro: 

    10 mM in DMSO

    Preparing
    Stock Solutions
    Concentration Solvent Mass 1 mg 5 mg 10 mg
    1 mM 1.3334 mL 6.6672 mL 13.3344 mL
    5 mM 0.2667 mL 1.3334 mL 2.6669 mL
    10 mM 0.1333 mL 0.6667 mL 1.3334 mL
    *Please refer to the solubility information to select the appropriate solvent.
    In Vivo:
    • 1.

      Simeprevir is prepared in vehicle (ddH2O)[3].

    References
    Kinase Assay
    [1]

    In vitro inhibition of NS3/4A activity 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.

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

    Cell Assay
    [1]

    Huh7-Luc cells are seeded at a density of 2,500 cells/well in a 384-well plate in Dulbecco's modified Eagle's 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.

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

    Animal Administration
    [1]

    Twenty-four male specific-pathogen-free Sprague-Dawley rats, weighing between 200 and 300 g at the time of dosing, are divided into eight groups of three rats each. Seven groups are dosed orally (p.o.) by gastric intubation of a vitamin E acetate-d-α-tocopheryl polyethylene glycol 1000 succinate-polyethylene glycol 400 solution of Simeprevir (TMC435350) at 2 mL/kg body weight to provide a dose of 40 mg/kg. One group is dosed intravenously (i.v.) by slow bolus injection in a tail vein of a 20% 2-hydroxypropyl-β-cyclodextrin formulation of TMC435350 (containing TMC435350, 100 mg/mL 2-hydroxypropyl-β-cyclodextrin, 0.1 N NaOH to pH 8.0±0.1, and mannitol-and pyrogen-free water) at 2 mL/kg body weight to provide a dose of 4 mg/kg. Water and food are available ad libitum during the study.

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

    References
    Molecular Weight

    749.94

    Formula

    C₃₈H₄₇N₅O₇S₂

    CAS No.

    923604-59-5

    SMILES

    COC1=C(C)C2=C(C(O[[email protected]]3CC(C(N(C)CCCC/C=C\[[email protected]](C4)[[email protected]]4(C(NS(=O)(C5CC5)=O)=O)N6)=O)[[email protected]](C6=O)C3)=CC(C7=NC(C(C)C)=CS7)=N2)C=C1

    Storage
    Powder -20°C 3 years
      4°C 2 years
    In solvent -80°C 6 months
      -20°C 1 month
    Shipping

    Room temperature in continental US; may vary elsewhere

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    Product Name:
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    Cat. No.:
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    Cat. No.: HY-10241