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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 No
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

CNS Penetrant
2588
Curator's Comment: There was minimal penetration of the blood-brain barrier.

Originator

Tibotec
10
Curator's Comment: Patent application WO2008092954A2 is a formulation patent, originally filed by Tibotec Pharmaceuticals, now part of Janssen Pharmaceuticals. The application claims a crystalline form of a substituted macro cyclic compound, preferably a variant of simeprevir, useful for the treatment of HCV infections.

Approval Year

2013
589
Targets

Targets

Primary TargetPharmacologyConditionPotency
Inhibitor
8504
 0.36 nM [Ki]
Conditions

Conditions

ConditionModalityTargetsHighest PhaseProduct
Primary
Approved
8583
OLYSIO

Approved Use

Indicated for the treatment of chronic hepatitis C (CHC) genotype 1 or 4 infection as a component of a combination antiviral treatment regimen. OLYSIO monotherapy is not recommended.

Launch Date

2013
Cmax

Cmax

ValueDoseCo-administeredAnalytePopulation
2304 ng/mL
EXPERIMENT
https://pubmed.ncbi.nlm.nih.gov/19852962/
200 mg single, oral
dose: 200 mg
route of administration: Oral
experiment type: SINGLE
co-administered:
SIMEPREVIR plasma
Homo sapiens
population: HEALTHY
age: ADULT
sex: FEMALE / MALE
food status: UNKNOWN
6172 ng/mL
EXPERIMENT
https://pubmed.ncbi.nlm.nih.gov/19852962/
200 mg 1 times / day multiple, oral
dose: 200 mg
route of administration: Oral
experiment type: MULTIPLE
co-administered:
SIMEPREVIR plasma
Homo sapiens
population: HEALTHY
age: ADULT
sex: FEMALE / MALE
food status: UNKNOWN
4067 ng/mL
EXPERIMENT
https://pubmed.ncbi.nlm.nih.gov/19852962/
200 mg single, oral
dose: 200 mg
route of administration: Oral
experiment type: SINGLE
co-administered:
SIMEPREVIR plasma
Homo sapiens
population: UNHEALTHY
age: ADULT
sex: FEMALE / MALE
food status: UNKNOWN
11470 ng/mL
EXPERIMENT
https://pubmed.ncbi.nlm.nih.gov/19852962/
200 mg 1 times / day multiple, oral
dose: 200 mg
route of administration: Oral
experiment type: MULTIPLE
co-administered:
SIMEPREVIR plasma
Homo sapiens
population: UNHEALTHY
age: ADULT
sex: FEMALE / MALE
food status: UNKNOWN
AUC

AUC

ValueDoseCo-administeredAnalytePopulation
24630 ng × h/mL
EXPERIMENT
https://pubmed.ncbi.nlm.nih.gov/19852962/
200 mg single, oral
dose: 200 mg
route of administration: Oral
experiment type: SINGLE
co-administered:
SIMEPREVIR plasma
Homo sapiens
population: HEALTHY
age: ADULT
sex: FEMALE / MALE
food status: UNKNOWN
79710 ng × h/mL
EXPERIMENT
https://pubmed.ncbi.nlm.nih.gov/19852962/
200 mg 1 times / day multiple, oral
dose: 200 mg
route of administration: Oral
experiment type: MULTIPLE
co-administered:
SIMEPREVIR plasma
Homo sapiens
population: HEALTHY
age: ADULT
sex: FEMALE / MALE
food status: UNKNOWN
56430 ng × h/mL
EXPERIMENT
https://pubmed.ncbi.nlm.nih.gov/19852962/
200 mg single, oral
dose: 200 mg
route of administration: Oral
experiment type: SINGLE
co-administered:
SIMEPREVIR plasma
Homo sapiens
population: UNHEALTHY
age: ADULT
sex: FEMALE / MALE
food status: UNKNOWN
206000 ng × h/mL
EXPERIMENT
https://pubmed.ncbi.nlm.nih.gov/19852962/
200 mg 1 times / day multiple, oral
dose: 200 mg
route of administration: Oral
experiment type: MULTIPLE
co-administered:
SIMEPREVIR plasma
Homo sapiens
population: UNHEALTHY
age: ADULT
sex: FEMALE / MALE
food status: UNKNOWN
T1/2

T1/2

ValueDoseCo-administeredAnalytePopulation
16.04 h
EXPERIMENT
https://pubmed.ncbi.nlm.nih.gov/19852962/
200 mg 1 times / day multiple, oral
dose: 200 mg
route of administration: Oral
experiment type: MULTIPLE
co-administered:
SIMEPREVIR plasma
Homo sapiens
population: HEALTHY
age: ADULT
sex: FEMALE / MALE
food status: UNKNOWN
41.32 h
EXPERIMENT
https://pubmed.ncbi.nlm.nih.gov/19852962/
200 mg 1 times / day multiple, oral
dose: 200 mg
route of administration: Oral
experiment type: MULTIPLE
co-administered:
SIMEPREVIR plasma
Homo sapiens
population: UNHEALTHY
age: ADULT
sex: FEMALE / MALE
food status: UNKNOWN
Doses

Doses

DosePopulationAdverse events​
200 mg 1 times / day multiple, oral
Dose: 200 mg, 1 times / day
Route: oral
Route: multiple
Dose: 200 mg, 1 times / day
Sources:
https://pubmed.ncbi.nlm.nih.gov/22326470
unhealthy, 18–70 years
Health Status: unhealthy
Age Group: 18–70 years
Sex: M+F
Sources:
https://pubmed.ncbi.nlm.nih.gov/22326470
Other AEs: Headache, Diarrhoea...
Other AEs:
Headache (13.5%)
Diarrhoea (10.8%)
Fatigue (10.8%)
Pruritus (10.8%)
Anorexia (8.1%)
Back pain (8.1%)
Myalgia (8.1%)
Sources:
https://pubmed.ncbi.nlm.nih.gov/22326470
400 mg 1 times / day multiple, oral
Highest studied dose
Dose: 400 mg, 1 times / day
Route: oral
Route: multiple
Dose: 400 mg, 1 times / day
Sources:
https://pubmed.ncbi.nlm.nih.gov/19852962
healthy, 24.0 years(range: 20-44 years)
Health Status: healthy
Age Group: 24.0 years(range: 20-44 years)
Sex: M+F
Sources:
https://pubmed.ncbi.nlm.nih.gov/19852962
Sources:
https://pubmed.ncbi.nlm.nih.gov/19852962
600 mg single, oral
Highest studied dose
Dose: 600 mg
Route: oral
Route: single
Dose: 600 mg
Sources:
https://pubmed.ncbi.nlm.nih.gov/19852962
healthy, 38.0 years (range: 23-55 years)
Health Status: healthy
Age Group: 38.0 years (range: 23-55 years)
Sex: M
Sources:
https://pubmed.ncbi.nlm.nih.gov/19852962
Sources:
https://pubmed.ncbi.nlm.nih.gov/19852962
200 mg 2 times / day multiple, oral
Highest studied dose
Dose: 200 mg, 2 times / day
Route: oral
Route: multiple
Dose: 200 mg, 2 times / day
Sources:
https://pubmed.ncbi.nlm.nih.gov/19852962
healthy, 38.0 years (range: 25-54 years)
Health Status: healthy
Age Group: 38.0 years (range: 25-54 years)
Sex: M+F
Sources:
https://pubmed.ncbi.nlm.nih.gov/19852962
Other AEs: Photosensitivity reaction, Diarrhea...
Other AEs:
Photosensitivity reaction (3 patients)
Diarrhea (2 patients)
Abdominal pain upper (2 patients)
Sources:
https://pubmed.ncbi.nlm.nih.gov/19852962
150 mg 1 times / day steady, oral
Recommended
Dose: 150 mg, 1 times / day
Route: oral
Route: steady
Dose: 150 mg, 1 times / day
Sources:
https://www.accessdata.fda.gov/drugsatfda_docs/nda/2013/205123Orig1s000MedR.pdf
unhealthy, 49 years (range: 18-73 years)
Health Status: unhealthy
Age Group: 49 years (range: 18-73 years)
Sex: M+F
Sources:
https://www.accessdata.fda.gov/drugsatfda_docs/nda/2013/205123Orig1s000MedR.pdf
Disc. AE: Pruritus, Psoriasis...
AEs leading to
discontinuation/dose reduction:
Pruritus (<1%)
Psoriasis (<1%)
Rash (1%)
Rash erythematous (<1%)
Skin burning sensation (<1%)
Aggression (<1%)
Blood bilirubin increased (<1%)
Major depression (<1%)
Stomatitis (<1%)
Headache (<1%)
Pain (<1%)
Sources:
https://www.accessdata.fda.gov/drugsatfda_docs/nda/2013/205123Orig1s000MedR.pdf
AEs

AEs

AESignificanceDosePopulation
Diarrhoea 10.8%
200 mg 1 times / day multiple, oral
Dose: 200 mg, 1 times / day
Route: oral
Route: multiple
Dose: 200 mg, 1 times / day
Sources:
https://pubmed.ncbi.nlm.nih.gov/22326470
unhealthy, 18–70 years
Health Status: unhealthy
Age Group: 18–70 years
Sex: M+F
Sources:
https://pubmed.ncbi.nlm.nih.gov/22326470
Fatigue 10.8%
200 mg 1 times / day multiple, oral
Dose: 200 mg, 1 times / day
Route: oral
Route: multiple
Dose: 200 mg, 1 times / day
Sources:
https://pubmed.ncbi.nlm.nih.gov/22326470
unhealthy, 18–70 years
Health Status: unhealthy
Age Group: 18–70 years
Sex: M+F
Sources:
https://pubmed.ncbi.nlm.nih.gov/22326470
Pruritus 10.8%
200 mg 1 times / day multiple, oral
Dose: 200 mg, 1 times / day
Route: oral
Route: multiple
Dose: 200 mg, 1 times / day
Sources:
https://pubmed.ncbi.nlm.nih.gov/22326470
unhealthy, 18–70 years
Health Status: unhealthy
Age Group: 18–70 years
Sex: M+F
Sources:
https://pubmed.ncbi.nlm.nih.gov/22326470
Headache 13.5%
200 mg 1 times / day multiple, oral
Dose: 200 mg, 1 times / day
Route: oral
Route: multiple
Dose: 200 mg, 1 times / day
Sources:
https://pubmed.ncbi.nlm.nih.gov/22326470
unhealthy, 18–70 years
Health Status: unhealthy
Age Group: 18–70 years
Sex: M+F
Sources:
https://pubmed.ncbi.nlm.nih.gov/22326470
Anorexia 8.1%
200 mg 1 times / day multiple, oral
Dose: 200 mg, 1 times / day
Route: oral
Route: multiple
Dose: 200 mg, 1 times / day
Sources:
https://pubmed.ncbi.nlm.nih.gov/22326470
unhealthy, 18–70 years
Health Status: unhealthy
Age Group: 18–70 years
Sex: M+F
Sources:
https://pubmed.ncbi.nlm.nih.gov/22326470
Back pain 8.1%
200 mg 1 times / day multiple, oral
Dose: 200 mg, 1 times / day
Route: oral
Route: multiple
Dose: 200 mg, 1 times / day
Sources:
https://pubmed.ncbi.nlm.nih.gov/22326470
unhealthy, 18–70 years
Health Status: unhealthy
Age Group: 18–70 years
Sex: M+F
Sources:
https://pubmed.ncbi.nlm.nih.gov/22326470
Myalgia 8.1%
200 mg 1 times / day multiple, oral
Dose: 200 mg, 1 times / day
Route: oral
Route: multiple
Dose: 200 mg, 1 times / day
Sources:
https://pubmed.ncbi.nlm.nih.gov/22326470
unhealthy, 18–70 years
Health Status: unhealthy
Age Group: 18–70 years
Sex: M+F
Sources:
https://pubmed.ncbi.nlm.nih.gov/22326470
Abdominal pain upper 2 patients
200 mg 2 times / day multiple, oral
Highest studied dose
Dose: 200 mg, 2 times / day
Route: oral
Route: multiple
Dose: 200 mg, 2 times / day
Sources:
https://pubmed.ncbi.nlm.nih.gov/19852962
healthy, 38.0 years (range: 25-54 years)
Health Status: healthy
Age Group: 38.0 years (range: 25-54 years)
Sex: M+F
Sources:
https://pubmed.ncbi.nlm.nih.gov/19852962
Diarrhea 2 patients
200 mg 2 times / day multiple, oral
Highest studied dose
Dose: 200 mg, 2 times / day
Route: oral
Route: multiple
Dose: 200 mg, 2 times / day
Sources:
https://pubmed.ncbi.nlm.nih.gov/19852962
healthy, 38.0 years (range: 25-54 years)
Health Status: healthy
Age Group: 38.0 years (range: 25-54 years)
Sex: M+F
Sources:
https://pubmed.ncbi.nlm.nih.gov/19852962
Photosensitivity reaction 3 patients
200 mg 2 times / day multiple, oral
Highest studied dose
Dose: 200 mg, 2 times / day
Route: oral
Route: multiple
Dose: 200 mg, 2 times / day
Sources:
https://pubmed.ncbi.nlm.nih.gov/19852962
healthy, 38.0 years (range: 25-54 years)
Health Status: healthy
Age Group: 38.0 years (range: 25-54 years)
Sex: M+F
Sources:
https://pubmed.ncbi.nlm.nih.gov/19852962
Rash 1%
Disc. AE
150 mg 1 times / day steady, oral
Recommended
Dose: 150 mg, 1 times / day
Route: oral
Route: steady
Dose: 150 mg, 1 times / day
Sources:
https://www.accessdata.fda.gov/drugsatfda_docs/nda/2013/205123Orig1s000MedR.pdf
unhealthy, 49 years (range: 18-73 years)
Health Status: unhealthy
Age Group: 49 years (range: 18-73 years)
Sex: M+F
Sources:
https://www.accessdata.fda.gov/drugsatfda_docs/nda/2013/205123Orig1s000MedR.pdf
Aggression <1%
Disc. AE
150 mg 1 times / day steady, oral
Recommended
Dose: 150 mg, 1 times / day
Route: oral
Route: steady
Dose: 150 mg, 1 times / day
Sources:
https://www.accessdata.fda.gov/drugsatfda_docs/nda/2013/205123Orig1s000MedR.pdf
unhealthy, 49 years (range: 18-73 years)
Health Status: unhealthy
Age Group: 49 years (range: 18-73 years)
Sex: M+F
Sources:
https://www.accessdata.fda.gov/drugsatfda_docs/nda/2013/205123Orig1s000MedR.pdf
Blood bilirubin increased <1%
Disc. AE
150 mg 1 times / day steady, oral
Recommended
Dose: 150 mg, 1 times / day
Route: oral
Route: steady
Dose: 150 mg, 1 times / day
Sources:
https://www.accessdata.fda.gov/drugsatfda_docs/nda/2013/205123Orig1s000MedR.pdf
unhealthy, 49 years (range: 18-73 years)
Health Status: unhealthy
Age Group: 49 years (range: 18-73 years)
Sex: M+F
Sources:
https://www.accessdata.fda.gov/drugsatfda_docs/nda/2013/205123Orig1s000MedR.pdf
Headache <1%
Disc. AE
150 mg 1 times / day steady, oral
Recommended
Dose: 150 mg, 1 times / day
Route: oral
Route: steady
Dose: 150 mg, 1 times / day
Sources:
https://www.accessdata.fda.gov/drugsatfda_docs/nda/2013/205123Orig1s000MedR.pdf
unhealthy, 49 years (range: 18-73 years)
Health Status: unhealthy
Age Group: 49 years (range: 18-73 years)
Sex: M+F
Sources:
https://www.accessdata.fda.gov/drugsatfda_docs/nda/2013/205123Orig1s000MedR.pdf
Major depression <1%
Disc. AE
150 mg 1 times / day steady, oral
Recommended
Dose: 150 mg, 1 times / day
Route: oral
Route: steady
Dose: 150 mg, 1 times / day
Sources:
https://www.accessdata.fda.gov/drugsatfda_docs/nda/2013/205123Orig1s000MedR.pdf
unhealthy, 49 years (range: 18-73 years)
Health Status: unhealthy
Age Group: 49 years (range: 18-73 years)
Sex: M+F
Sources:
https://www.accessdata.fda.gov/drugsatfda_docs/nda/2013/205123Orig1s000MedR.pdf
Pain <1%
Disc. AE
150 mg 1 times / day steady, oral
Recommended
Dose: 150 mg, 1 times / day
Route: oral
Route: steady
Dose: 150 mg, 1 times / day
Sources:
https://www.accessdata.fda.gov/drugsatfda_docs/nda/2013/205123Orig1s000MedR.pdf
unhealthy, 49 years (range: 18-73 years)
Health Status: unhealthy
Age Group: 49 years (range: 18-73 years)
Sex: M+F
Sources:
https://www.accessdata.fda.gov/drugsatfda_docs/nda/2013/205123Orig1s000MedR.pdf
Pruritus <1%
Disc. AE
150 mg 1 times / day steady, oral
Recommended
Dose: 150 mg, 1 times / day
Route: oral
Route: steady
Dose: 150 mg, 1 times / day
Sources:
https://www.accessdata.fda.gov/drugsatfda_docs/nda/2013/205123Orig1s000MedR.pdf
unhealthy, 49 years (range: 18-73 years)
Health Status: unhealthy
Age Group: 49 years (range: 18-73 years)
Sex: M+F
Sources:
https://www.accessdata.fda.gov/drugsatfda_docs/nda/2013/205123Orig1s000MedR.pdf
Psoriasis <1%
Disc. AE
150 mg 1 times / day steady, oral
Recommended
Dose: 150 mg, 1 times / day
Route: oral
Route: steady
Dose: 150 mg, 1 times / day
Sources:
https://www.accessdata.fda.gov/drugsatfda_docs/nda/2013/205123Orig1s000MedR.pdf
unhealthy, 49 years (range: 18-73 years)
Health Status: unhealthy
Age Group: 49 years (range: 18-73 years)
Sex: M+F
Sources:
https://www.accessdata.fda.gov/drugsatfda_docs/nda/2013/205123Orig1s000MedR.pdf
Rash erythematous <1%
Disc. AE
150 mg 1 times / day steady, oral
Recommended
Dose: 150 mg, 1 times / day
Route: oral
Route: steady
Dose: 150 mg, 1 times / day
Sources:
https://www.accessdata.fda.gov/drugsatfda_docs/nda/2013/205123Orig1s000MedR.pdf
unhealthy, 49 years (range: 18-73 years)
Health Status: unhealthy
Age Group: 49 years (range: 18-73 years)
Sex: M+F
Sources:
https://www.accessdata.fda.gov/drugsatfda_docs/nda/2013/205123Orig1s000MedR.pdf
Skin burning sensation <1%
Disc. AE
150 mg 1 times / day steady, oral
Recommended
Dose: 150 mg, 1 times / day
Route: oral
Route: steady
Dose: 150 mg, 1 times / day
Sources:
https://www.accessdata.fda.gov/drugsatfda_docs/nda/2013/205123Orig1s000MedR.pdf
unhealthy, 49 years (range: 18-73 years)
Health Status: unhealthy
Age Group: 49 years (range: 18-73 years)
Sex: M+F
Sources:
https://www.accessdata.fda.gov/drugsatfda_docs/nda/2013/205123Orig1s000MedR.pdf
Stomatitis <1%
Disc. AE
150 mg 1 times / day steady, oral
Recommended
Dose: 150 mg, 1 times / day
Route: oral
Route: steady
Dose: 150 mg, 1 times / day
Sources:
https://www.accessdata.fda.gov/drugsatfda_docs/nda/2013/205123Orig1s000MedR.pdf
unhealthy, 49 years (range: 18-73 years)
Health Status: unhealthy
Age Group: 49 years (range: 18-73 years)
Sex: M+F
Sources:
https://www.accessdata.fda.gov/drugsatfda_docs/nda/2013/205123Orig1s000MedR.pdf
Overview

Overview

CYP3A4CYP2C9CYP2D6hERG
substrate
1946

inducer
1087
inhibitor
2438
inhibitor
2507
inhibitor
2217

OverviewOther

Other InhibitorOther SubstrateOther Inducer
CYP2A6
879

CYP2C8
1057

CYP2C19
2057

CYP3A
227

OATP1B1
1079

NTCP
39

P-gp
1741

MRP2
499

BSEP
550

CYP1A
70

CYP2E1
1060
CYP2C8
810

CYP2C19
1119

P-gp
2052

MRP2
252

BCRP
697

OATP1B1/3
11

OATP2B1
122
CYP1A2
832
Drug as perpetrator​

Drug as perpetrator​

TargetModalityActivityMetaboliteClinical evidence
CYP2D6
2546
 moderate [IC50 42.9 uM]
CYP2C8
1117
 moderate [IC50 49.1 uM]
CYP2A6
911
 moderate [IC50 59.7 uM]
CYP1A
122
 no
CYP1A2
2333
 no
CYP2C9
2497
 no
CYP2E1
1146
 no
CYP3A4
2633
 no
CYP3A
317
 weak [IC50 131 uM]
likely (co-administration study)
Comment: Concomitant use of OLYSIO with these antiarrhythmics may result in mild increases in concentrations of these antiarrhythmics due to intestinal CYP3A4 inhibition by simeprevir
Page: 37.0
CYP2C19
2141
 weak [IC50 86.1 uM]
BSEP
554
 yes [IC50 1.67 uM]
OATP1B1
1095
 yes [IC50 25 uM]
yes (co-administration study)
Comment: Concomitant use of OLYSIO with rosuvastatin resulted in increased plasma concentrations of rosuvastatin due to inhibition of OATP1B1 by simeprevir
Page: 38.0
NTCP
40
 yes [IC50 3.47 uM]
MRP2
625
 yes [IC50 6.4 uM]
P-gp
1932
 yes [IC50 85.9 uM]
yes (co-administration study)
Comment: Concomitant use of OLYSIO with digoxin resulted in increased concentrations of digoxin due to inhibition of P-gp by simeprevir
Page: 38.0
Drug as victim

Drug as victim

TargetModalityActivityMetaboliteClinical evidence
BCRP
697
 yes
CYP2C19
1119
 yes
CYP2C8
810
 yes
MRP2
252
 yes
OATP1B1/3
11
 yes
OATP2B1
122
 yes
P-gp
2052
 yes
CYP3A4
1946
 yes
likely (co-administration study)
Comment: Concomitant use of OLYSIO with carbamazepine, oxcarbazepine, phenobarbital or phenytoin may result in significantly decreased plasma concentrations of simeprevir due to strong CYP3A induction by these anticonvulsants; Concomitant use of OLYSIO with clarithromycin or telithromycin may result in increased plasma concentrations of simeprevir due to CYP3A inhibition by these antibiotics
Page: 37.0
Tox targets

Tox targets

TargetModalityActivityMetaboliteClinical evidence
hERG
2263
Sourcing

Sourcing

Vendor/AggregatorIDURL
AChemBlock
R16014
AK Scientific
4041AH
AstaTech
33532
Chem Scene
CS-0338
eMolecules
313130810
Hangzhou APIChem Technology
AC-27651
Innovapharm
VT-00687829
KeyOrganics
AS-56205
Lan Pharmatech
LQT-B48548
mcule
MCULE-6850465396
mcule
MCULE-7634361057
MedChem Express
HY-10241
MolPort
MolPort-039-139-798
MolPort
MolPort-046-416-844
MolPort
MolPort-046-795-603
MuseChem
I009489
TargetMol
T4686
ZINC
ZINC000253632968
http://zinc15.docking.org/substances/ZINC000253632968
PubMed

PubMed

TitleDatePubMed
Advances in the development of macrocyclic inhibitors of hepatitis C virus NS3-4A protease.
2010
Synthesis and antiviral activity of novel HCV NS3 protease inhibitors with P4 capping groups.
2012 Dec 15
Changing the face of hepatitis C management - the design and development of sofosbuvir.
2015
Patents

Patents

20090281140
2
CN104473941A
2

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 Mar 31 19:11:36 GMT 2025
Edited
by admin
on Mon Mar 31 19:11:36 GMT 2025
Record UNII
9WS5RD66HZ
Record Status Validated (UNII)
Record Version
  • Download
Name Type Language
TMC 435
Preferred Name English
SIMEPREVIR
DASH   INN   USAN   VANDF   WHO-DD  
USAN   INN  
Official Name English
TMC435
Common Name English
TMC435350
Code English
TMC 435350
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 [WHO-DD]
Common Name English
SIMEPREVIR [USAN]
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 Mar 31 19:11:36 GMT 2025 , Edited by admin on Mon Mar 31 19:11:36 GMT 2025
WHO-ATC J05AP05
Created by admin on Mon Mar 31 19:11:36 GMT 2025 , Edited by admin on Mon Mar 31 19:11:36 GMT 2025
WHO-ATC J05AE14
Created by admin on Mon Mar 31 19:11:36 GMT 2025 , Edited by admin on Mon Mar 31 19:11:36 GMT 2025
NDF-RT N0000182639
Created by admin on Mon Mar 31 19:11:36 GMT 2025 , Edited by admin on Mon Mar 31 19:11:36 GMT 2025
Code System Code Type Description
NDF-RT
N0000182638
Created by admin on Mon Mar 31 19:11:36 GMT 2025 , Edited by admin on Mon Mar 31 19:11:36 GMT 2025
PRIMARY HCV NS3/4A Protease Inhibitors [MoA]
FDA UNII
9WS5RD66HZ
Created by admin on Mon Mar 31 19:11:36 GMT 2025 , Edited by admin on Mon Mar 31 19:11:36 GMT 2025
PRIMARY
NCI_THESAURUS
C129015
Created by admin on Mon Mar 31 19:11:36 GMT 2025 , Edited by admin on Mon Mar 31 19:11:36 GMT 2025
PRIMARY
DRUG BANK
DB06290
Created by admin on Mon Mar 31 19:11:36 GMT 2025 , Edited by admin on Mon Mar 31 19:11:36 GMT 2025
PRIMARY
WIKIPEDIA
Simeprevir
Created by admin on Mon Mar 31 19:11:36 GMT 2025 , Edited by admin on Mon Mar 31 19:11:36 GMT 2025
PRIMARY
IUPHAR
7367
Created by admin on Mon Mar 31 19:11:36 GMT 2025 , Edited by admin on Mon Mar 31 19:11:36 GMT 2025
PRIMARY
NDF-RT
N0000185503
Created by admin on Mon Mar 31 19:11:36 GMT 2025 , Edited by admin on Mon Mar 31 19:11:36 GMT 2025
PRIMARY P-Glycoprotein Inhibitors [MoA]
USAN
XX-54
Created by admin on Mon Mar 31 19:11:36 GMT 2025 , Edited by admin on Mon Mar 31 19:11:36 GMT 2025
PRIMARY
DRUG CENTRAL
4812
Created by admin on Mon Mar 31 19:11:36 GMT 2025 , Edited by admin on Mon Mar 31 19:11:36 GMT 2025
PRIMARY
PUBCHEM
24873435
Created by admin on Mon Mar 31 19:11:36 GMT 2025 , Edited by admin on Mon Mar 31 19:11:36 GMT 2025
PRIMARY
ChEMBL
CHEMBL501849
Created by admin on Mon Mar 31 19:11:36 GMT 2025 , Edited by admin on Mon Mar 31 19:11:36 GMT 2025
PRIMARY
NDF-RT
N0000182141
Created by admin on Mon Mar 31 19:11:36 GMT 2025 , Edited by admin on Mon Mar 31 19:11:36 GMT 2025
PRIMARY Cytochrome P450 3A4 Inhibitors [MoA]
CAS
1217263-04-1
Created by admin on Mon Mar 31 19:11:36 GMT 2025 , Edited by admin on Mon Mar 31 19:11:36 GMT 2025
NON-SPECIFIC STEREOCHEMISTRY
CAS
923604-59-5
Created by admin on Mon Mar 31 19:11:36 GMT 2025 , Edited by admin on Mon Mar 31 19:11:36 GMT 2025
PRIMARY
NDF-RT
N0000190107
Created by admin on Mon Mar 31 19:11:36 GMT 2025 , Edited by admin on Mon Mar 31 19:11:36 GMT 2025
PRIMARY Organic Anion Transporting Polypeptide 1B1 Inhibitors [MoA]
INN
9432
Created by admin on Mon Mar 31 19:11:36 GMT 2025 , Edited by admin on Mon Mar 31 19:11:36 GMT 2025
PRIMARY
LACTMED
Simeprevir
Created by admin on Mon Mar 31 19:11:36 GMT 2025 , Edited by admin on Mon Mar 31 19:11:36 GMT 2025
PRIMARY
SMS_ID
100000134797
Created by admin on Mon Mar 31 19:11:36 GMT 2025 , Edited by admin on Mon Mar 31 19:11:36 GMT 2025
PRIMARY
HSDB
8227
Created by admin on Mon Mar 31 19:11:36 GMT 2025 , Edited by admin on Mon Mar 31 19:11:36 GMT 2025
PRIMARY
EVMPD
SUB64783
Created by admin on Mon Mar 31 19:11:36 GMT 2025 , Edited by admin on Mon Mar 31 19:11:36 GMT 2025
PRIMARY
MERCK INDEX
m11694
Created by admin on Mon Mar 31 19:11:36 GMT 2025 , Edited by admin on Mon Mar 31 19:11:36 GMT 2025
PRIMARY
EPA CompTox
DTXSID20919221
Created by admin on Mon Mar 31 19:11:36 GMT 2025 , Edited by admin on Mon Mar 31 19:11:36 GMT 2025
PRIMARY
RXCUI
1482790
Created by admin on Mon Mar 31 19:11:36 GMT 2025 , Edited by admin on Mon Mar 31 19:11:36 GMT 2025
PRIMARY RxNorm
NDF-RT
N0000190108
Created by admin on Mon Mar 31 19:11:36 GMT 2025 , Edited by admin on Mon Mar 31 19:11:36 GMT 2025
PRIMARY Organic Anion Transporting Polypeptide 1B3 Inhibitors [MoA]
Related Record Type Details
Structure of SIMEPREVIR
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
CYTOCHROME P450 3A4
METABOLIC ENZYME -> INHIBITOR
WEAK
IC50
MULTIDRUG RESISTANCE PROTEIN 1
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
OATP1B1
TRANSPORTER -> SUBSTRATE
Structure of SIMEPREVIR SODIUM
SALT/SOLVATE -> PARENT
OATP-8
TRANSPORTER -> SUBSTRATE
OATP-B
TRANSPORTER -> SUBSTRATE
HEPATITIS C VIRUS GENOTYPE 1
TARGET ORGANISM->INHIBITOR
Specifically used for hepatitis C genotype 1 and 4.
CYTOCHROME P450 2C19
METABOLIC ENZYME -> INHIBITOR
WEAK
IC50
CYTOCHROME P450 2C8
METABOLIC ENZYME -> SUBSTRATE
CYTOCHROME P450 3A4
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).
CYTOCHROME P450 2C19
METABOLIC ENZYME -> SUBSTRATE
HCV NS3-4A SERINE PROTEASE
TARGET -> INHIBITOR
PLASMA PROTEIN FRACTION (HUMAN)
BINDER->LIGAND
BINDING
MULTIDRUG RESISTANCE PROTEIN 1
TRANSPORTER -> SUBSTRATE
CYTOCHROME P450 2C8
METABOLIC ENZYME -> INHIBITOR
CYP2C8
IC50
CYTOCHROME P450 2A6
METABOLIC ENZYME -> INHIBITOR
MODERATE
IC50
HEPATITIS C VIRUS
TARGET ORGANISM->INHIBITOR
CYTOCHROME P450 2D6
METABOLIC ENZYME -> INHIBITOR
CYP2C8
IC50
Related Record Type Details
Structure of SIMEPREVIR
ACTIVE MOIETY
Name Property Type Amount Referenced Substance Defining Parameters References
Tmax PHARMACOKINETIC
Biological Half-life PHARMACOKINETIC
NIH
NCATS
PRIVACY ACT
ACCESSIBILITY
DISCLAIMER
HHS VULNERABILITY DISCLOSURE
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