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Details

Stereochemistry ABSOLUTE
Molecular Formula C38H47N5O7S2
Molecular Weight 749.939
Optical Activity UNSPECIFIED
Defined Stereocenters 5 / 5
E/Z Centers 0
Charge 0

SHOW SMILES / InChI
Structure of SIMEPREVIR

SMILES

COC1=CC=C2C(O[C@@H]3C[C@@H]4[C@@H](C3)C(=O)N(C)CCCCC=C[C@@H]5C[C@]5(NC4=O)C(=O)NS(=O)(=O)C6CC6)=CC(=NC2=C1C)C7=NC(=CS7)C(C)C

InChI

InChIKey=JTZZSQYMACOLNN-VDWJNHBNSA-N
InChI=1S/C38H47N5O7S2/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,(H,41,44)(H,42,46)/b10-8-/t23-,24-,27-,28-,38-/m1/s1

HIDE SMILES / InChI

Molecular Formula C38H47N5O7S2
Molecular Weight 749.939
Charge 0
Count
Stereochemistry ABSOLUTE
Additional Stereochemistry
Defined Stereocenters 5 / 5
E/Z Centers 0
Optical Activity UNSPECIFIED

Description

Simeprevir is a hepatitis C virus (HCV) NS3/4A protease inhibitor approved for the treatment of Chronic Hepatitis C (genotype 1 and 4). Inhibiting NS3/4A, simeprevir blocks viral replication. In in vitro assays simeprevir was potent against HCV genotype 1a and 1b. Simeprevir must not be administered as monotherapy and should only be prescribed with both peginterferon alfa and ribavirin.

CNS Activity

Originator

Approval Year

Targets

Targets

Primary TargetPharmacologyConditionPotency
0.36 nM [Ki]
Conditions

Conditions

PubMed

PubMed

TitleDatePubMed
In vitro activity and preclinical profile of TMC435350, a potent hepatitis C virus protease inhibitor.
2009 Apr
Advances in the development of macrocyclic inhibitors of hepatitis C virus NS3-4A protease.
2010
Improved P2 phenylglycine-based hepatitis C virus NS3 protease inhibitors with alkenylic prime-side substituents.
2010 Jul 15
Differential efficacy of protease inhibitors against HCV genotypes 2a, 3a, 5a, and 6a NS3/4A protease recombinant viruses.
2011 Sep
Discovery of novel urea-based hepatitis C protease inhibitors with high potency against protease-inhibitor-resistant mutants.
2012 Apr 12
Synthesis and antiviral activity of novel HCV NS3 protease inhibitors with P4 capping groups.
2012 Dec 15
Highly efficient infectious cell culture of three hepatitis C virus genotype 2b strains and sensitivity to lead protease, nonstructural protein 5A, and polymerase inhibitors.
2014 Feb
Changing the face of hepatitis C management - the design and development of sofosbuvir.
2015
Cost-effectiveness of sofosbuvir-based treatments for chronic hepatitis C in the US.
2015 Aug 5
Hepatitis C virus: Virology, diagnosis and treatment.
2015 Jun 8
Interferon-free therapy for hepatitis C: The hurdles amid a golden era.
2015 Sep
Patents

Sample Use Guides

In Vivo Use Guide
The recommended dose is one 150 mg capsule taken once daily with food. OLYSIO should be administered with both peginterferon alfa and ribavirin. The recommended treatment duration of OLYSIO with peginterferon alfa and ribavirin is 12 weeks, followed by either 12 or 36 additional weeks of peginterferon alfa and ribavirin depending on prior response status.
Route of Administration: Oral
In Vitro Use Guide
The median simeprevir EC50 and EC90 values against a HCV genotype 1b replicon were 9.4 nM (7.05 ng/mL) and 19 nM (14.25 ng/mL), respectively.
Substance Class Chemical
Created
by admin
on Mon Oct 21 19:46:58 UTC 2019
Edited
by admin
on Mon Oct 21 19:46:58 UTC 2019
Record UNII
9WS5RD66HZ
Record Status Validated (UNII)
Record Version
  • Download
Name Type Language
SIMEPREVIR
DASH   INN   USAN   VANDF   WHO-DD  
USAN   INN  
Official Name English
TMC435
Common Name English
TMC435350
Code English
TMC 435350
Code English
TMC 435
Code English
SIMEPREVIR [VANDF]
Common Name English
SIMEPREVIR [JAN]
Common Name English
SIMEPREVIR [INN]
Common Name English
SIMEPREVIR SODIUM [JAN]
Common Name English
TMC-435
Code English
SIMEPREVIR [USAN]
Common Name English
SIMEPREVIR [WHO-DD]
Common Name English
SIMEPREVIR [MI]
Common Name English
TMC-435350
Code English
Classification Tree Code System Code
NCI_THESAURUS C783
Created by admin on Mon Oct 21 19:46:58 UTC 2019 , Edited by admin on Mon Oct 21 19:46:58 UTC 2019
WHO-ATC J05AP05
Created by admin on Mon Oct 21 19:46:58 UTC 2019 , Edited by admin on Mon Oct 21 19:46:58 UTC 2019
WHO-ATC J05AE14
Created by admin on Mon Oct 21 19:46:58 UTC 2019 , Edited by admin on Mon Oct 21 19:46:58 UTC 2019
NDF-RT N0000182639
Created by admin on Mon Oct 21 19:46:58 UTC 2019 , Edited by admin on Mon Oct 21 19:46:58 UTC 2019
Code System Code Type Description
LactMed
923604-59-5
Created by admin on Mon Oct 21 19:46:58 UTC 2019 , Edited by admin on Mon Oct 21 19:46:58 UTC 2019
PRIMARY
NDF-RT
N0000182638
Created by admin on Mon Oct 21 19:46:58 UTC 2019 , Edited by admin on Mon Oct 21 19:46:58 UTC 2019
PRIMARY HCV NS3/4A Protease Inhibitors [MoA]
NCI_THESAURUS
C129015
Created by admin on Mon Oct 21 19:46:58 UTC 2019 , Edited by admin on Mon Oct 21 19:46:58 UTC 2019
PRIMARY
DRUG BANK
DB06290
Created by admin on Mon Oct 21 19:46:58 UTC 2019 , Edited by admin on Mon Oct 21 19:46:58 UTC 2019
PRIMARY
WIKIPEDIA
Simeprevir
Created by admin on Mon Oct 21 19:46:58 UTC 2019 , Edited by admin on Mon Oct 21 19:46:58 UTC 2019
PRIMARY
IUPHAR
7367
Created by admin on Mon Oct 21 19:46:58 UTC 2019 , Edited by admin on Mon Oct 21 19:46:58 UTC 2019
PRIMARY
NDF-RT
N0000185503
Created by admin on Mon Oct 21 19:46:58 UTC 2019 , Edited by admin on Mon Oct 21 19:46:58 UTC 2019
PRIMARY P-Glycoprotein Inhibitors [MoA]
PUBCHEM
24873435
Created by admin on Mon Oct 21 19:46:58 UTC 2019 , Edited by admin on Mon Oct 21 19:46:58 UTC 2019
PRIMARY
ChEMBL
CHEMBL501849
Created by admin on Mon Oct 21 19:46:58 UTC 2019 , Edited by admin on Mon Oct 21 19:46:58 UTC 2019
PRIMARY
NDF-RT
N0000182141
Created by admin on Mon Oct 21 19:46:58 UTC 2019 , Edited by admin on Mon Oct 21 19:46:58 UTC 2019
PRIMARY Cytochrome P450 3A4 Inhibitors [MoA]
CAS
1217263-04-1
Created by admin on Mon Oct 21 19:46:58 UTC 2019 , Edited by admin on Mon Oct 21 19:46:58 UTC 2019
NON-SPECIFIC STEREOCHEMISTRY
CAS
923604-59-5
Created by admin on Mon Oct 21 19:46:58 UTC 2019 , Edited by admin on Mon Oct 21 19:46:58 UTC 2019
PRIMARY
NDF-RT
N0000190107
Created by admin on Mon Oct 21 19:46:58 UTC 2019 , Edited by admin on Mon Oct 21 19:46:58 UTC 2019
PRIMARY Organic Anion Transporting Polypeptide 1B1 Inhibitors [MoA]
INN
9432
Created by admin on Mon Oct 21 19:46:58 UTC 2019 , Edited by admin on Mon Oct 21 19:46:58 UTC 2019
PRIMARY
HSDB
923604-59-5
Created by admin on Mon Oct 21 19:46:58 UTC 2019 , Edited by admin on Mon Oct 21 19:46:58 UTC 2019
PRIMARY
EVMPD
SUB64783
Created by admin on Mon Oct 21 19:46:58 UTC 2019 , Edited by admin on Mon Oct 21 19:46:58 UTC 2019
PRIMARY
MERCK INDEX
M11694
Created by admin on Mon Oct 21 19:46:58 UTC 2019 , Edited by admin on Mon Oct 21 19:46:58 UTC 2019
PRIMARY
RXCUI
1482790
Created by admin on Mon Oct 21 19:46:58 UTC 2019 , Edited by admin on Mon Oct 21 19:46:58 UTC 2019
PRIMARY RxNorm
NDF-RT
N0000190108
Created by admin on Mon Oct 21 19:46:58 UTC 2019 , Edited by admin on Mon Oct 21 19:46:58 UTC 2019
PRIMARY Organic Anion Transporting Polypeptide 1B3 Inhibitors [MoA]
Related Record Type Details
EXCRETED UNCHANGED
Results from the mass balance trial demonstrated that the majority of the simeprevir dose is absorbed, with only 31.0% of dose excreted as unchanged drug in the feces (Trial C103).
FECAL
METABOLIC ENZYME -> INHIBITOR
WEAK
IC50
TRANSPORTER -> INHIBITOR
Simeprevir inhibited P-gp-dependent transport of paclitaxel in Caco-2 cells with an IC50 value of 64.4 ug/mL (Study NC113).
IC50
TRANSPORTER -> SUBSTRATE
SALT/SOLVATE -> PARENT
TRANSPORTER -> SUBSTRATE
TRANSPORTER -> SUBSTRATE
TARGET ORGANISM->INHIBITOR
Specifically used for hepatitis C genotype 1 and 4.
METABOLIC ENZYME -> INHIBITOR
WEAK
IC50
METABOLIC ENZYME -> SUBSTRATE
METABOLIC ENZYME -> SUBSTRATE
Plasma concentration will significantly increase if taken with medications that are strong CYP3A4 inhibitors (i.e. erythromycin, ritonavir) and will significantly decrease if taken with strong CYP3A4 inducers (i.e. efavirenz, rifampin, Saint John's wort).
METABOLIC ENZYME -> SUBSTRATE
BINDER->LIGAND
BINDING
TRANSPORTER -> SUBSTRATE
METABOLIC ENZYME -> INHIBITOR
CYP2C8
IC50
METABOLIC ENZYME -> INHIBITOR
MODERATE
IC50
TARGET ORGANISM->INHIBITOR
METABOLIC ENZYME -> INHIBITOR
CYP2C8
IC50
TARGET -> INHIBITOR
INHIBITOR
Related Record Type Details
ACTIVE MOIETY
Name Property Type Amount Referenced Substance Defining Parameters References
Tmax PHARMACOKINETIC
Biological Half-life PHARMACOKINETIC