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

Simeprevir (Synonyms: TMC435)

Cat. No.: HY-10241 Purity: 99.98%
Data Sheet SDS 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 $198 In-stock
5 mg $120 In-stock
10 mg $210 In-stock
50 mg $890 In-stock
100 mg $1500 In-stock
200 mg   Get quote  
500 mg   Get quote  

* Please select Quantity before adding items.

    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).
    • 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
    View MoreCollapse
    References
    Preparing Stock Solutions
    Concentration Volume 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.
    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]

    Simeprevir is diluted in in a final DMSO concentration of 0.5% in the absence of G418.

    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

    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

    Solvent & Solubility

    10 mM in DMSO

    * "<1 mg/mL" means slightly soluble or insoluble. "≥" means soluble, but saturation unknown.

    Inquiry Online

    Your information is safe with us. * Required Fields.

    Product name

     

    Salutation

    Applicant name *

     

    Email address *

    Phone number

     

    Organization name *

    Country *

     

    Requested quantity *

    Remarks

    Bulk Inquiry

    Inquiry Information

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