research use only

Simeprevir HCV Protease inhibitor

Name: Simeprevir
Brand: Selleck Chemicals
SKU: S5015
Availability: InStock
Rating: 5 (7 reviews)

Cat.No.S5015

Simeprevir is a competitive, reversible, macrocyclic, noncovalent hepatitis C virus (HCV) NS3/4A protease inhibitor that acts directly against the hepatitis C virus. It has a medium inhibitory concentration (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.

Chemical Structure

Molecular Weight: 749.94

Jump to

Quality Control

Batch: Purity: 99.99%

99.99

Related Targets	HDAC Caspase Proteasome Secretase MMP Cysteine Protease Tyrosinase DPP HIV Protease Serine Protease
Other HCV Protease Inhibitors	Danoprevir Lomibuvir (VX-222) Asunaprevir Tizoxanide PSI-6206 (GS-331007) 2'-C-Methylcytidine Tegobuvir Herba taxilli Extract Mecarbinate

Solubility

In vitro
Batch:

DMSO : 100 mg/mL (133.34 mM)
(Moisture-contaminated DMSO may reduce solubility. Use fresh, anhydrous DMSO.)

Ethanol : 4 mg/mL

Water : Insoluble

Molarity Calculator

Mass	Concentration	Volume	Molecular Weight
Mass value Mass unit	Concentration value Concentration unit	Volume value Volume unit	Molecular weight (g/mol)

Dilution Calculator Molecular Weight Calculator

In vivo batch selection In vivo Batch:
Homogeneous suspension	CMC-NA	≥5mg/ml	Taking the 1 mL working solution as an example, add 5 mg of this product to 1 ml of CMC-Na solution, mix evenly to obtain a homogeneous suspension with a final concentration of 5 mg/ml.
Homogeneous suspension	CMC-NA	≥5mg/ml	Taking the 1 mL working solution as an example, add 5 mg of this product to 1 ml of CMC-Na solution, mix evenly to obtain a homogeneous suspension with a final concentration of 5 mg/ml.
Clear solution	5%DMSO 1 40%PEG300 2 5%Tween80 3 50%ddH2O Validated by Selleck labs. Should you need adjustments to this formulation, contact our sales team for custom testing.	0.830mg/ml (1.11mM)	Taking the 1 mL working solution as an example, add 50 μL of 16.6 mg/ml clarified DMSO stock solution to 400 μL of PEG300, mix evenly to clarify it; add 50 μL of Tween80 to the above system, mix evenly to clarify; then continue to add 500 μL of ddH2O to adjust the volume to 1 mL. The mixed solution should be used immediately for optimal results.
Clear solution	5% DMSO 1 95% Corn oil Validated by Selleck labs. Should you need adjustments to this formulation, contact our sales team for custom testing.	0.830mg/ml (1.11mM)	Taking the 1 mL working solution as an example, add 50 μL of 16.6 mg/ml clear DMSO stock solution to 950 μL of corn oil and mix evenly. The mixed solution should be used immediately for optimal results.

In vivo Formulation Calculator (Clear solution)

Step 1: Enter information below (Recommended: An additional animal making an allowance for loss during the experiment)

Dosage: mg/kg

Average weight of animals: g

Dosing volume per animal: μL

Number of animals:

Step 2: Enter the in vivo formulation (This is only the calculator, not formulation. Please contact us first if there is no in vivo formulation at the solubility Section.)

% DMSO

% Tween 80

% ddH₂O

% DMSO

Calculation results:

Working concentration: mg/ml;

Method for preparing DMSO master liquid: mg drug pre-dissolved in μL DMSO ( Master liquid 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 master liquid, next addμL PEG300, mix and clarify, next addμL Tween 80, mix and clarify, next add μL ddH₂O, mix and clarify.

Method for preparing in vivo formulation: Take μL DMSO master liquid, next add μL Corn oil, mix and clarify.

Note: 1. Please make sure the liquid is clear before adding the next solvent.
2. Be sure to add the solvent(s) in order. You must ensure that the solution obtained, in the previous addition, is a clear solution before proceeding to add the next solvent. Physical methods such
as vortex, ultrasound or hot water bath can be used to aid dissolving.

Chemical Information, Storage & Stability

Molecular Weight	749.94	Formula	C₃₈H₄₇N₅O₇S₂	Storage (From the date of receipt)	3 years-20°Cpowder
CAS No.	923604-59-5	--		Storage of Stock Solutions	1 year-80°Cin solvent 1 month-20°Cin solvent
Synonyms	TMC435, TMC-435350			Smiles	CC1=C(C=CC2=C1N=C(C=C2OC3CC4C(C3)C(=O)N(CCCCC=CC5CC5(NC4=O)C(=O)NS(=O)(=O)C6CC6)C)C7=NC(=CS7)C(C)C)OC

Mechanism of Action

Targets/IC₅₀/Ki	HCV NS3/4A protease
In vitro	Simeprevir exhibits potent inhibition on NS3/4A protease of genotypes 1a, 1b, 2, 4, 5, and 6, with a medium inhibitory concentration (IC50) <13 nM for all HCV NS3/4A enzymes tested. However, the IC50 for genotype 3 is 37 nM. In vitro, this compound is also an inhibitor of bilirubin transporters OATP1B1 and MRP2. It is a more potent inhibitor of OATP1B1 (IC50=720 nM), which is primarily responsible for transporting unconjugated bilirubin, than MRP2 (IC50 around 10,000 nM), primarily a conjugated bilirubin transporter.
In vivo	In vivo, simeprevir has a relatively long absorption phase, reaching maximum concentration (Cmax) after 4-6 hours. It is extensively (99.9%) bound to plasma proteins, mainly to albumin. The absolute bioavailability is 44% after a single oral administration. In rats, the liver to blood ratio is 29:1, which means good distribution to the liver. For humans, in preclinical studies, the liver to plasma concentration ratio is really high (ratio of 39). The highest tissue/plasma AUC ratios are observed in the small intestine (ratio of 128). While tissue concentrations of this compound reach peak values within 4 hours postdosing, its concentrations in liver remain above the EC99 for up to 31 hours postdosing, and plasma concentrations are higher than the EC99 at 8 hours and around the EC50 at 24 hours postdosing. The AUC24h of this chemical is increased by 61%-69% when administered with food. It should therefore be taken with food. This compound is also a substrate and inhibitor of P-glycoprotein. It is metabolized by CYP3A4 and eliminated by biliary excretion. It is also an inhibitor of gut cytochrome 3A4 but not hepatic CYP3A4.
References	[1] https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4157399/#b20-pgpm-7-241

Clinical Trial Information

(data from https://clinicaltrials.gov, updated on 2024-05-22)

NCT Number	Recruitment	Conditions	Sponsor/Collaborators	Start Date	Phases
NCT03277755	Withdrawn	Hepatic Impairment	Janssen Research & Development LLC	September 11 2017	Phase 1
NCT02404805	Completed	HIV\|Hepatitis C	University of Colorado Denver	February 2016	Not Applicable
NCT02569710	Completed	Chronic Hepatitis C	Alios Biopharma Inc.	October 31 2015	Phase 2
NCT02512562	Completed	Chronic Hepatitis C	Alios Biopharma Inc.\|Alexion Pharmaceuticals Inc.	July 31 2015	Phase 1

Tech Support

Handling Instructions

Tel: +1-832-582-8158 Ext:3

If you have any other enquiries, please leave a message.

C1=C0/X	C1:	LOG(C1):
C2=C1/X	C2:	LOG(C2):
C3=C2/X	C3:	LOG(C3):
C4=C3/X	C4:	LOG(C4):
C5=C4/X	C5:	LOG(C5):
C6=C5/X	C6:	LOG(C6):
C7=C6/X	C7:	LOG(C7):
C8=C7/X	C8:	LOG(C8):