U.S. Department of Health & Human Services Divider Arrow National Institutes of Health Divider Arrow NCATS

Details

Stereochemistry MIXED
Molecular Formula C27H45N5O5
Molecular Weight 519.6767
Optical Activity UNSPECIFIED
Defined Stereocenters 4 / 5
E/Z Centers 0
Charge 0

SHOW SMILES / InChI
Structure of BOCEPREVIR

SMILES

CC(C)(C)NC(=O)N[C@H](C(=O)N1C[C@H]2[C@@H]([C@H]1C(=O)NC(CC3CCC3)C(=O)C(N)=O)C2(C)C)C(C)(C)C

InChI

InChIKey=LHHCSNFAOIFYRV-DOVBMPENSA-N
InChI=1S/C27H45N5O5/c1-25(2,3)20(30-24(37)31-26(4,5)6)23(36)32-13-15-17(27(15,7)8)18(32)22(35)29-16(19(33)21(28)34)12-14-10-9-11-14/h14-18,20H,9-13H2,1-8H3,(H2,28,34)(H,29,35)(H2,30,31,37)/t15-,16?,17-,18-,20+/m0/s1

HIDE SMILES / InChI

Description
Curator's Comment: description was created based on several sources, including https://www.ncbi.nlm.nih.gov/pubmed/?term=26357603

Boceprevir (trade name Victrelis) is first-generation, selective, small molecule inhibitor of the non-structural serine protease (NS3) and NS4A polypeptide complex (NS3/NS4A) and is a direct acting antiviral drug against the hepatitis C virus. It is indicated the treatment of chronic hepatitis C (CHC) genotype 1 infection, in combination with peginterferon alfa and ribavirin, in adult patients (18 years of age and older) with compensated liver disease, including cirrhosis, who are previously untreated or who have failed previous interferon and ribavirin therapy. Boceprevir is not approved as a monotherapy. Upon administration, boceprevir reversibly binds to the active center of the HCV NS3/NS4A and prevents NS3/NS4A protease-mediated polyprotein maturation. This disrupts the processing of viral proteins and the formation of a viral replication complex, which inhibits viral replication in HCV genotrype 1-infected host cells. NS3, a serine protease, is essential for the proteolytic cleavages within the HCV polyprotein and plays a key role during HCV viral RNA replication. NS4A is an activating factor for NS3.

Originator

Curator's Comment: # Merck Sharp & Dohme Corp., Whitehouse Station, NJ, USA

Approval Year

Targets

Targets

Primary TargetPharmacologyConditionPotency
14.0 nM [Ki]
Conditions

Conditions

ConditionModalityTargetsHighest PhaseProduct
Primary
VICTRELIS

Approved Use

Indicated for the treatment of chronic hepatitis C genotype 1 infection, in combination with peginterferon alfa and ribavirin, in adult patients with compensated liver disease, including cirrhosis, who are previously untreated or who have failed previous interferon and ribavirin therapy, including prior null responders, partial responders, and relapsers.

Launch Date

2011
Cmax

Cmax

ValueDoseCo-administeredAnalytePopulation
505 ng/mL
200 mg 3 times / day steady-state, oral
dose: 200 mg
route of administration: Oral
experiment type: STEADY-STATE
co-administered:
BOCEPREVIR plasma
Homo sapiens
population: HEALTHY
age: ADULT
sex: UNKNOWN
food status: UNKNOWN
881 ng/mL
400 mg 3 times / day steady-state, oral
dose: 400 mg
route of administration: Oral
experiment type: STEADY-STATE
co-administered:
BOCEPREVIR plasma
Homo sapiens
population: HEALTHY
age: ADULT
sex: UNKNOWN
food status: UNKNOWN
1680 ng/mL
800 mg 3 times / day steady-state, oral
dose: 800 mg
route of administration: Oral
experiment type: STEADY-STATE
co-administered:
BOCEPREVIR plasma
Homo sapiens
population: HEALTHY
age: ADULT
sex: UNKNOWN
food status: UNKNOWN
1940 ng/mL
1200 mg 3 times / day steady-state, oral
dose: 1200 mg
route of administration: Oral
experiment type: STEADY-STATE
co-administered:
BOCEPREVIR plasma
Homo sapiens
population: HEALTHY
age: ADULT
sex: UNKNOWN
food status: UNKNOWN
698 ng/mL
400 mg single, oral
dose: 400 mg
route of administration: Oral
experiment type: SINGLE
co-administered:
BOCEPREVIR plasma
Homo sapiens
population: HEALTHY
age: ADULT
sex: UNKNOWN
food status: HIGH-FAT
1710 ng/mL
800 mg single, oral
dose: 800 mg
route of administration: Oral
experiment type: SINGLE
co-administered:
BOCEPREVIR plasma
Homo sapiens
population: HEALTHY
age: ADULT
sex: UNKNOWN
food status: HIGH-FAT
339 ng/mL
200 mg single, oral
dose: 200 mg
route of administration: Oral
experiment type: SINGLE
co-administered:
BOCEPREVIR plasma
Homo sapiens
population: HEALTHY
age: ADULT
sex: UNKNOWN
food status: HIGH-FAT
1723 ng/mL
800 mg 3 times / day steady-state, oral
dose: 800 mg
route of administration: Oral
experiment type: STEADY-STATE
co-administered:
BOCEPREVIR unknown
Homo sapiens
population: HEALTHY
age: ADULT
sex: UNKNOWN
food status: UNKNOWN
AUC

AUC

ValueDoseCo-administeredAnalytePopulation
1330 ng × h/mL
200 mg 3 times / day steady-state, oral
dose: 200 mg
route of administration: Oral
experiment type: STEADY-STATE
co-administered:
BOCEPREVIR plasma
Homo sapiens
population: HEALTHY
age: ADULT
sex: UNKNOWN
food status: UNKNOWN
2620 ng × h/mL
400 mg 3 times / day steady-state, oral
dose: 400 mg
route of administration: Oral
experiment type: STEADY-STATE
co-administered:
BOCEPREVIR plasma
Homo sapiens
population: HEALTHY
age: ADULT
sex: UNKNOWN
food status: UNKNOWN
4830 ng × h/mL
800 mg 3 times / day steady-state, oral
dose: 800 mg
route of administration: Oral
experiment type: STEADY-STATE
co-administered:
BOCEPREVIR plasma
Homo sapiens
population: HEALTHY
age: ADULT
sex: UNKNOWN
food status: UNKNOWN
6500 ng × h/mL
1200 mg 3 times / day steady-state, oral
dose: 1200 mg
route of administration: Oral
experiment type: STEADY-STATE
co-administered:
BOCEPREVIR plasma
Homo sapiens
population: HEALTHY
age: ADULT
sex: UNKNOWN
food status: UNKNOWN
2100 ng × h/mL
400 mg single, oral
dose: 400 mg
route of administration: Oral
experiment type: SINGLE
co-administered:
BOCEPREVIR plasma
Homo sapiens
population: HEALTHY
age: ADULT
sex: UNKNOWN
food status: HIGH-FAT
6350 ng × h/mL
800 mg single, oral
dose: 800 mg
route of administration: Oral
experiment type: SINGLE
co-administered:
BOCEPREVIR plasma
Homo sapiens
population: HEALTHY
age: ADULT
sex: UNKNOWN
food status: HIGH-FAT
994 ng × h/mL
200 mg single, oral
dose: 200 mg
route of administration: Oral
experiment type: SINGLE
co-administered:
BOCEPREVIR plasma
Homo sapiens
population: HEALTHY
age: ADULT
sex: UNKNOWN
food status: HIGH-FAT
5408 ng × h/mL
800 mg 3 times / day steady-state, oral
dose: 800 mg
route of administration: Oral
experiment type: STEADY-STATE
co-administered:
BOCEPREVIR unknown
Homo sapiens
population: HEALTHY
age: ADULT
sex: UNKNOWN
food status: UNKNOWN
T1/2

T1/2

ValueDoseCo-administeredAnalytePopulation
3.5 h
200 mg 3 times / day steady-state, oral
dose: 200 mg
route of administration: Oral
experiment type: STEADY-STATE
co-administered:
BOCEPREVIR plasma
Homo sapiens
population: HEALTHY
age: ADULT
sex: UNKNOWN
food status: UNKNOWN
5.1 h
400 mg 3 times / day steady-state, oral
dose: 400 mg
route of administration: Oral
experiment type: STEADY-STATE
co-administered:
BOCEPREVIR plasma
Homo sapiens
population: HEALTHY
age: ADULT
sex: UNKNOWN
food status: UNKNOWN
10.2 h
800 mg 3 times / day steady-state, oral
dose: 800 mg
route of administration: Oral
experiment type: STEADY-STATE
co-administered:
BOCEPREVIR plasma
Homo sapiens
population: HEALTHY
age: ADULT
sex: UNKNOWN
food status: UNKNOWN
3 h
1200 mg 3 times / day steady-state, oral
dose: 1200 mg
route of administration: Oral
experiment type: STEADY-STATE
co-administered:
BOCEPREVIR plasma
Homo sapiens
population: HEALTHY
age: ADULT
sex: UNKNOWN
food status: UNKNOWN
1.9 h
400 mg single, oral
dose: 400 mg
route of administration: Oral
experiment type: SINGLE
co-administered:
BOCEPREVIR plasma
Homo sapiens
population: HEALTHY
age: ADULT
sex: UNKNOWN
food status: HIGH-FAT
3 h
800 mg single, oral
dose: 800 mg
route of administration: Oral
experiment type: SINGLE
co-administered:
BOCEPREVIR plasma
Homo sapiens
population: HEALTHY
age: ADULT
sex: UNKNOWN
food status: HIGH-FAT
2.1 h
200 mg single, oral
dose: 200 mg
route of administration: Oral
experiment type: SINGLE
co-administered:
BOCEPREVIR plasma
Homo sapiens
population: HEALTHY
age: ADULT
sex: UNKNOWN
food status: HIGH-FAT
3.4 h
800 mg 3 times / day steady-state, oral
dose: 800 mg
route of administration: Oral
experiment type: STEADY-STATE
co-administered:
BOCEPREVIR unknown
Homo sapiens
population: HEALTHY
age: ADULT
sex: UNKNOWN
food status: UNKNOWN
Funbound

Funbound

ValueDoseCo-administeredAnalytePopulation
25%
800 mg 3 times / day steady-state, oral
dose: 800 mg
route of administration: Oral
experiment type: STEADY-STATE
co-administered:
BOCEPREVIR unknown
Homo sapiens
population: HEALTHY
age: ADULT
sex: UNKNOWN
food status: UNKNOWN
Doses

Doses

DosePopulationAdverse events​
800 mg 3 times / day steady, oral
Recommended
Dose: 800 mg, 3 times / day
Route: oral
Route: steady
Dose: 800 mg, 3 times / day
Sources:
healthy, 18-60 years
n = 13
Health Status: healthy
Age Group: 18-60 years
Sex: M
Population Size: 13
Sources:
400 mg single, oral
Dose: 400 mg
Route: oral
Route: single
Dose: 400 mg
Sources:
unhealthy, 18–65 years
n = 6
Health Status: unhealthy
Condition: Severe hepatic impairment
Age Group: 18–65 years
Sex: M
Population Size: 6
Sources:
Other AEs: Vomiting...
Other AEs:
Vomiting (1 patient)
Sources:
400 mg 3 times / day steady, oral
Dose: 400 mg, 3 times / day
Route: oral
Route: steady
Dose: 400 mg, 3 times / day
Sources:
unhealthy, 40.7 years
n = 6
Health Status: unhealthy
Condition: hepatitis C genotype 2/3 infection
Age Group: 40.7 years
Sex: M+F
Population Size: 6
Sources:
AEs

AEs

AESignificanceDosePopulation
Vomiting 1 patient
400 mg single, oral
Dose: 400 mg
Route: oral
Route: single
Dose: 400 mg
Sources:
unhealthy, 18–65 years
n = 6
Health Status: unhealthy
Condition: Severe hepatic impairment
Age Group: 18–65 years
Sex: M
Population Size: 6
Sources:
Overview

Overview

Drug as perpetrator​

Drug as perpetrator​

TargetModalityActivityMetaboliteClinical evidence
minimal [IC50 >100 uM]
minimal [IC50 >100 uM]
minimal [IC50 >100 uM]
minimal [IC50 >100 uM]
minimal [IC50 >100 uM]
no
no
no
no
no
strong [IC50 11 uM]
yes (co-administration study)
Comment: Boceprevir increased the AUC and Cmax of midazolam by 5- and 2.5-fold, respectively, relative to midazolam alone. This result confirms that boceprevir is a strong inhibitor of CYP3A4. Therefore, boceprevir should not be coadministered with sensitive substrates of CYP3A4 with a narrow therapeutic index; efavirenz decreased the mean Cmax, AUC0-8h, and Cmin of boceprevir by 8%, 19%, and 44%, respectively, during co-administration
Page: 23;78
weak [IC50 >100 uM]
yes [IC50 18 uM]
yes [IC50 25 uM]
yes [IC50 81 uM]
yes [Ki 7.7 uM]
weak (co-administration study)
Comment: competitive inhibition; Boceprevir increased the mean Cmax and AUC0-24h of efavirenz by 11% and 20%, respectively, during co-administration relative to efavirenz alone; Boceprevir increased the mean Cmax, AUC0-24h, and Cmin of drospirenone by 57%, 99%, and 143%, respectively, during co-administration relative to Yaz® alone; boceprevir decreased the mean AUC0-24h and Cmin of ethinyl estradiol by 24% and 31%, respectively, during co-administration relative to Yaz® alone
Page: 264.0
Drug as victimTox targets

Tox targets

TargetModalityActivityMetaboliteClinical evidence
PubMed

PubMed

TitleDatePubMed
Identification and analysis of fitness of resistance mutations against the HCV protease inhibitor SCH 503034.
2006 Jun
Discovery of (1R,5S)-N-[3-amino-1-(cyclobutylmethyl)-2,3-dioxopropyl]- 3-[2(S)-[[[(1,1-dimethylethyl)amino]carbonyl]amino]-3,3-dimethyl-1-oxobutyl]- 6,6-dimethyl-3-azabicyclo[3.1.0]hexan-2(S)-carboxamide (SCH 503034), a selective, potent, orally bioavailable hepatitis C virus NS3 protease inhibitor: a potential therapeutic agent for the treatment of hepatitis C infection.
2006 Oct 5
Inhibitors of hepatitis C virus NS3/4A: alpha-ketoamide based macrocyclic inhibitors.
2009 Apr 15
MK-7009, a potent and selective inhibitor of hepatitis C virus NS3/4A protease.
2010 Jan
Preclinical characterization of BI 201335, a C-terminal carboxylic acid inhibitor of the hepatitis C virus NS3-NS4A protease.
2010 Nov
Estimation of inhibitory quotient using a comparative equilibrium dialysis assay for prediction of viral response to hepatitis C virus inhibitors.
2011 May
Differential efficacy of protease inhibitors against HCV genotypes 2a, 3a, 5a, and 6a NS3/4A protease recombinant viruses.
2011 Sep
In vitro efficacy of approved and experimental antivirals against novel genotype 3 hepatitis C virus subgenomic replicons.
2013 Nov
Patents

Sample Use Guides

800 mg administered orally three times daily (every 7 to 9 hours) with food (a meal or light snack). Victrelis must be administered in combination with peginterferon alfa and ribavirin. Initiate therapy with peginterferon alfa and ribavirin for 4 weeks, then add Victerelis to peginterferon alfa and ribavirin regimen. The duration of treatment is based on viral response, prior response status and presence of cirrhosis.
Route of Administration: Oral
The EC50 and EC90 values for boceprevir against an HCV replicon constructed from a single genotype 1b isolate were approximately 200 nM and 400 nM, respectively, in a 72-hour cell culture assay. Boceprevir cell culture anti-HCV activity was approximately 2-fold lower for an HCV replicon derived from a single genotype 1a isolate, relative to the 1b isolate-derived replicon. In replicon assays, boceprevir had approximately 2-fold reduced activity against a genotype 2a isolate relative to genotype 1a and 1b replicon isolates.
Name Type Language
BOCEPREVIR
DASH   EMA EPAR   INN   MART.   MI   ORANGE BOOK   USAN   VANDF   WHO-DD  
USAN   INN  
Official Name English
BOCEPREVIR [EMA EPAR]
Common Name English
SCH 503034
Code English
BOCEPREVIR [MI]
Common Name English
EBP 520
Code English
BOCEPREVIR [USAN]
Common Name English
BOCEPREVIR [MART.]
Common Name English
boceprevir [INN]
Common Name English
EBP-520
Code English
Boceprevir [WHO-DD]
Common Name English
SCH-503034
Code English
BOCEPREVIR [ORANGE BOOK]
Common Name English
VICTRELIS
Brand Name English
BOCEPREVIR [VANDF]
Common Name English
(1R,2S,5S)-N-[3-Amino-1-(cyclobutylmethyl)-2,3-dioxopropyl]-3-[(2S)-2-[[(1,1-dimethylethyl)carbamoyl]amino]-3,3-dimethylbutanoyl]-6,6-dimethyl-3-azabicyclo[3.1.0]hexane-2-carboxamide
Systematic Name English
3-AZABICYCLO(3.1.0)HEXANE-2-CARBOXAMIDE, N-(3-AMINO-1-(CYCLOBUTYLMETHYL)-2,3-DIOXOPROPYL)-3-((2S)-2-((((1,1-DIMETHYLETHYL)AMINO)CARBONYL)AMINO)-3,3-DIMETHYL-1-OXOBUTYL)-6,6-DIMETHYL-, (1R,2S,5S)-
Systematic Name English
Classification Tree Code System Code
EMA ASSESSMENT REPORTS VICTRELIS (AUTHORIZED: HEPATITIS C, CHRONIC)
Created by admin on Fri Dec 15 15:40:03 GMT 2023 , Edited by admin on Fri Dec 15 15:40:03 GMT 2023
WHO-VATC QJ05AE12
Created by admin on Fri Dec 15 15:40:03 GMT 2023 , Edited by admin on Fri Dec 15 15:40:03 GMT 2023
WHO-ATC J05AP03
Created by admin on Fri Dec 15 15:40:03 GMT 2023 , Edited by admin on Fri Dec 15 15:40:03 GMT 2023
LIVERTOX NBK548247
Created by admin on Fri Dec 15 15:40:03 GMT 2023 , Edited by admin on Fri Dec 15 15:40:03 GMT 2023
WHO-ATC J05AP03
Created by admin on Fri Dec 15 15:40:03 GMT 2023 , Edited by admin on Fri Dec 15 15:40:03 GMT 2023
NCI_THESAURUS C281
Created by admin on Fri Dec 15 15:40:03 GMT 2023 , Edited by admin on Fri Dec 15 15:40:03 GMT 2023
NDF-RT N0000182639
Created by admin on Fri Dec 15 15:40:03 GMT 2023 , Edited by admin on Fri Dec 15 15:40:03 GMT 2023
WHO-ATC J05AE12
Created by admin on Fri Dec 15 15:40:03 GMT 2023 , Edited by admin on Fri Dec 15 15:40:03 GMT 2023
Code System Code Type Description
CHEBI
68621
Created by admin on Fri Dec 15 15:40:03 GMT 2023 , Edited by admin on Fri Dec 15 15:40:03 GMT 2023
PRIMARY
FDA UNII
89BT58KELH
Created by admin on Fri Dec 15 15:40:03 GMT 2023 , Edited by admin on Fri Dec 15 15:40:03 GMT 2023
PRIMARY
EPA CompTox
DTXSID30960103
Created by admin on Fri Dec 15 15:40:03 GMT 2023 , Edited by admin on Fri Dec 15 15:40:03 GMT 2023
PRIMARY
DRUG CENTRAL
4172
Created by admin on Fri Dec 15 15:40:03 GMT 2023 , Edited by admin on Fri Dec 15 15:40:03 GMT 2023
PRIMARY
MERCK INDEX
m2592
Created by admin on Fri Dec 15 15:40:03 GMT 2023 , Edited by admin on Fri Dec 15 15:40:03 GMT 2023
PRIMARY Merck Index
HSDB
8081
Created by admin on Fri Dec 15 15:40:03 GMT 2023 , Edited by admin on Fri Dec 15 15:40:03 GMT 2023
PRIMARY
LACTMED
Boceprevir
Created by admin on Fri Dec 15 15:40:03 GMT 2023 , Edited by admin on Fri Dec 15 15:40:03 GMT 2023
PRIMARY
INN
8840
Created by admin on Fri Dec 15 15:40:03 GMT 2023 , Edited by admin on Fri Dec 15 15:40:03 GMT 2023
PRIMARY
EVMPD
SUB31579
Created by admin on Fri Dec 15 15:40:03 GMT 2023 , Edited by admin on Fri Dec 15 15:40:03 GMT 2023
PRIMARY
CAS
394730-60-0
Created by admin on Fri Dec 15 15:40:03 GMT 2023 , Edited by admin on Fri Dec 15 15:40:03 GMT 2023
PRIMARY
RXCUI
1102129
Created by admin on Fri Dec 15 15:40:03 GMT 2023 , Edited by admin on Fri Dec 15 15:40:03 GMT 2023
PRIMARY RxNorm
NDF-RT
N0000182141
Created by admin on Fri Dec 15 15:40:03 GMT 2023 , Edited by admin on Fri Dec 15 15:40:03 GMT 2023
PRIMARY Cytochrome P450 3A4 Inhibitors [MoA]
DRUG BANK
DB08873
Created by admin on Fri Dec 15 15:40:03 GMT 2023 , Edited by admin on Fri Dec 15 15:40:03 GMT 2023
PRIMARY
USAN
N07/04
Created by admin on Fri Dec 15 15:40:03 GMT 2023 , Edited by admin on Fri Dec 15 15:40:03 GMT 2023
PRIMARY
ChEMBL
CHEMBL218394
Created by admin on Fri Dec 15 15:40:03 GMT 2023 , Edited by admin on Fri Dec 15 15:40:03 GMT 2023
PRIMARY
WIKIPEDIA
BOCEPREVIR
Created by admin on Fri Dec 15 15:40:03 GMT 2023 , Edited by admin on Fri Dec 15 15:40:03 GMT 2023
PRIMARY
NCI_THESAURUS
C117292
Created by admin on Fri Dec 15 15:40:03 GMT 2023 , Edited by admin on Fri Dec 15 15:40:03 GMT 2023
PRIMARY
SMS_ID
100000124138
Created by admin on Fri Dec 15 15:40:03 GMT 2023 , Edited by admin on Fri Dec 15 15:40:03 GMT 2023
PRIMARY
PUBCHEM
10324367
Created by admin on Fri Dec 15 15:40:03 GMT 2023 , Edited by admin on Fri Dec 15 15:40:03 GMT 2023
PRIMARY
NDF-RT
N0000182638
Created by admin on Fri Dec 15 15:40:03 GMT 2023 , Edited by admin on Fri Dec 15 15:40:03 GMT 2023
PRIMARY HCV NS3/4A Protease Inhibitors [MoA]