BOCEPREVIR

US Previously Marketed

First approved in 2011

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 Search

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
Sources: http://www.accessdata.fda.gov/drugsatfda_docs/label/2014/202258s015lbl.pdf
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

Approval Year

Targets

Primary Target	Pharmacology	Condition	Potency
Hepatitis C virus serine protease, NS3/NS4A 13 Target ID: CHEMBL2095231 Sources: http://www.accessdata.fda.gov/drugsatfda_docs/label/2014/202258s015lbl.pdf	Inhibitor 8297		14.0 nM [Ki]

Conditions

Condition	Modality	Targets	Highest Phase	Product
Chronic hepatitis C 42 Sources: http://www.accessdata.fda.gov/drugsatfda_docs/label/2014/202258s015lbl.pdf	Primary		Approved 8429	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

C_max

Value	Dose	Analyte	Population
505 ng/mL OTHER GOV https://www.accessdata.fda.gov/drugsatfda_docs/nda/2011/202258Orig1s000ClinPharmR.pdf	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 OTHER GOV https://www.accessdata.fda.gov/drugsatfda_docs/nda/2011/202258Orig1s000ClinPharmR.pdf	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 OTHER GOV https://www.accessdata.fda.gov/drugsatfda_docs/nda/2011/202258Orig1s000ClinPharmR.pdf	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 OTHER GOV https://www.accessdata.fda.gov/drugsatfda_docs/nda/2011/202258Orig1s000ClinPharmR.pdf	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 OTHER GOV https://www.accessdata.fda.gov/drugsatfda_docs/nda/2011/202258Orig1s000ClinPharmR.pdf	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 OTHER GOV https://www.accessdata.fda.gov/drugsatfda_docs/nda/2011/202258Orig1s000ClinPharmR.pdf	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 OTHER GOV https://www.accessdata.fda.gov/drugsatfda_docs/nda/2011/202258Orig1s000ClinPharmR.pdf	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 DRUG LABEL https://www.accessdata.fda.gov/drugsatfda_docs/label/2011/202258lbl.pdf	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

Value	Dose	Analyte	Population
1330 ng × h/mL OTHER GOV https://www.accessdata.fda.gov/drugsatfda_docs/nda/2011/202258Orig1s000ClinPharmR.pdf	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 OTHER GOV https://www.accessdata.fda.gov/drugsatfda_docs/nda/2011/202258Orig1s000ClinPharmR.pdf	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 OTHER GOV https://www.accessdata.fda.gov/drugsatfda_docs/nda/2011/202258Orig1s000ClinPharmR.pdf	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 OTHER GOV https://www.accessdata.fda.gov/drugsatfda_docs/nda/2011/202258Orig1s000ClinPharmR.pdf	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 OTHER GOV https://www.accessdata.fda.gov/drugsatfda_docs/nda/2011/202258Orig1s000ClinPharmR.pdf	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 OTHER GOV https://www.accessdata.fda.gov/drugsatfda_docs/nda/2011/202258Orig1s000ClinPharmR.pdf	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 OTHER GOV https://www.accessdata.fda.gov/drugsatfda_docs/nda/2011/202258Orig1s000ClinPharmR.pdf	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 DRUG LABEL https://www.accessdata.fda.gov/drugsatfda_docs/label/2011/202258lbl.pdf	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

T_1/2

Value	Dose	Analyte	Population
3.5 h OTHER GOV https://www.accessdata.fda.gov/drugsatfda_docs/nda/2011/202258Orig1s000ClinPharmR.pdf	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 OTHER GOV https://www.accessdata.fda.gov/drugsatfda_docs/nda/2011/202258Orig1s000ClinPharmR.pdf	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 OTHER GOV https://www.accessdata.fda.gov/drugsatfda_docs/nda/2011/202258Orig1s000ClinPharmR.pdf	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 OTHER GOV https://www.accessdata.fda.gov/drugsatfda_docs/nda/2011/202258Orig1s000ClinPharmR.pdf	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 OTHER GOV https://www.accessdata.fda.gov/drugsatfda_docs/nda/2011/202258Orig1s000ClinPharmR.pdf	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 OTHER GOV https://www.accessdata.fda.gov/drugsatfda_docs/nda/2011/202258Orig1s000ClinPharmR.pdf	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 OTHER GOV https://www.accessdata.fda.gov/drugsatfda_docs/nda/2011/202258Orig1s000ClinPharmR.pdf	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 DRUG LABEL https://www.accessdata.fda.gov/drugsatfda_docs/label/2011/202258lbl.pdf	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

F_unbound

Value	Dose	Co-administered	Analyte	Population
25% DRUG LABEL https://www.accessdata.fda.gov/drugsatfda_docs/label/2011/202258lbl.pdf	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

Dose	Population	Adverse 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: https://pubmed.ncbi.nlm.nih.gov/25693997	healthy, 18-60 years n = 13 Health Status: healthy Age Group: 18-60 years Sex: M Population Size: 13 Sources: https://pubmed.ncbi.nlm.nih.gov/25693997	Sources: https://pubmed.ncbi.nlm.nih.gov/25693997
400 mg single, oral Dose: 400 mg Route: oral Route: single Dose: 400 mg Sources: https://pubmed.ncbi.nlm.nih.gov/22799589	unhealthy, 18–65 years n = 6 Health Status: unhealthy Condition: Severe hepatic impairment Age Group: 18–65 years Sex: M Population Size: 6 Sources: https://pubmed.ncbi.nlm.nih.gov/22799589	Other AEs: Vomiting... Other AEs: Vomiting (1 patient) Sources: https://pubmed.ncbi.nlm.nih.gov/22799589
400 mg 3 times / day steady, oral Dose: 400 mg, 3 times / day Route: oral Route: steady Dose: 400 mg, 3 times / day Sources: https://pubmed.ncbi.nlm.nih.gov/23454058	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: https://pubmed.ncbi.nlm.nih.gov/23454058	Sources: https://pubmed.ncbi.nlm.nih.gov/23454058

AEs

AE	Significance	Dose	Population
Vomiting	1 patient	400 mg single, oral Dose: 400 mg Route: oral Route: single Dose: 400 mg Sources: https://pubmed.ncbi.nlm.nih.gov/22799589	unhealthy, 18–65 years n = 6 Health Status: unhealthy Condition: Severe hepatic impairment Age Group: 18–65 years Sex: M Population Size: 6 Sources: https://pubmed.ncbi.nlm.nih.gov/22799589

Overview

CYP3A4	CYP2C9	CYP2D6	hERG
substrate 1737 inhibitor 1587		inhibitor 1852	inhibitor 1612

OverviewOther

Other Inhibitor	Other Substrate	Other Inducer
P-gp 1461 CYP1A2 1524 CYP2A6 707 CYP2C8 911 CYP2C19 1478 CYP3A4/5 278 OATP1B1 788 BCRP 699 UGT2B7 146 UGT1A1 204 MRP2 383 OAT1 599 OAT3 642	AKR1C2 9 AKR1C3 13 P-gp 1537 OATP1B1 406 OATP1B3 350	CYP 450 10

Drug as perpetrator

Target	Modality	Activity	Clinical evidence
CYP1A2 1692	inhibitor 3277 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2011/202258Orig1s000ClinPharmR.pdf#page=264 Page: 264.0	minimal [IC50 >100 uM]
CYP2A6 739	inhibitor 3277 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2011/202258Orig1s000ClinPharmR.pdf#page=264 Page: 264.0	minimal [IC50 >100 uM]
CYP2C19 1553	inhibitor 3277 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2011/202258Orig1s000ClinPharmR.pdf#page=264 Page: 264.0	minimal [IC50 >100 uM]
CYP2C8 965	inhibitor 3277 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2011/202258Orig1s000ClinPharmR.pdf#page=264 Page: 264.0	minimal [IC50 >100 uM]
CYP2D6 1891	inhibitor 3277 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2011/202258Orig1s000ClinPharmR.pdf#page=264 Page: 264.0	minimal [IC50 >100 uM]
CYP 450 20	inducer 1573 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2011/202258Orig1s000ClinPharmR.pdf#page=78 Page: 78.0	no
MRP2 475	inhibitor 3277 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2011/202258Orig1s000ClinPharmR.pdf#page=10 Page: 10.0	no
OAT1 603	inhibitor 3277 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2011/202258Orig1s000ClinPharmR.pdf#page=82 Page: 82.0	no
OAT3 644	inhibitor 3277 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2011/202258Orig1s000ClinPharmR.pdf#page=82 Page: 82.0	no
UGT2B7 157	inhibitor 3277 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2011/202258Orig1s000ClinPharmR.pdf#page=2 Page: 2.0	no
CYP3A4 1925	inhibitor 3277 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2011/202258Orig1s000ClinPharmR.pdf#page=23 Page: 23;78	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 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2011/202258Orig1s000ClinPharmR.pdf#page=23 Page: 23;78
UGT1A1 254	inhibitor 3277 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2011/202258Orig1s000ClinPharmR.pdf#page=2 Page: 2;12	weak [IC50 >100 uM]
OATP1B1 803	inhibitor 3277 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2011/202258Orig1s000ClinPharmR.pdf#page=2 Page: 2.0	yes [IC50 18 uM]
P-gp 1650	inhibitor 3277 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2011/202258Orig1s000ClinPharmR.pdf#page=23 Page: 23;79	yes [IC50 25 uM]
BCRP 773	inhibitor 3277 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2011/202258Orig1s000ClinPharmR.pdf#page=2 Page: 2.0	yes [IC50 81 uM]
CYP3A4/5 335	inhibitor 3277 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2011/202258Orig1s000ClinPharmR.pdf#page=264 Page: 264.0	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 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2011/202258Orig1s000ClinPharmR.pdf#page=264 Page: 264.0

Drug as victim

Target	Modality	Activity	Clinical evidence
OATP1B1 406	substrate 3367 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2011/202258Orig1s000ClinPharmR.pdf#page=2 Page: 2.0	no
OATP1B3 350	substrate 3367 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2011/202258Orig1s000ClinPharmR.pdf#page=2 Page: 2.0	no
AKR1C2 9	substrate 3367 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2011/202258Orig1s000ClinPharmR.pdf#page=21 Page: 21.0	yes
AKR1C3 13	substrate 3367 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2011/202258Orig1s000ClinPharmR.pdf#page=21 Page: 21.0	yes
P-gp 1537	substrate 3367 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2011/202258Orig1s000ClinPharmR.pdf#page=23 Page: 23.0	yes
CYP3A4 1737	substrate 3367 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2011/202258Orig1s000ClinPharmR.pdf#page=23 Page: 23.0	yes	yes (co-administration study) Comment: Ketoconazole increased the AUC of boceprevir by 2.3-fold relative to boceprevir alone Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2011/202258Orig1s000ClinPharmR.pdf#page=23 Page: 23.0

Tox targets

Target	Modality	Activity	Metabolite	Clinical evidence
hERG 1647	inhibitor 1626 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2011/202258Orig1s000OtherR.pdf#page=48 Page: 48.0

Sourcing

Vendor/Aggregator	ID	URL
ChEBI	CHEBI:68621	https://www.ebi.ac.uk/chebi/searchId.do?chebiId=CHEBI:68621
MolPort	MolPort-006-170-107	https://www.molport.com/shop/molecule-link/MolPort-006-170-107
eMolecules	36752244	https://www.emolecules.com/cgi-bin/more?vid=36752244

PubMed

Title	Date	PubMed
Identification and analysis of fitness of resistance mutations against the HCV protease inhibitor SCH 503034.	2006 Jun	16448708
SCH 503034, a mechanism-based inhibitor of hepatitis C virus NS3 protease, suppresses polyprotein maturation and enhances the antiviral activity of alpha interferon in replicon cells.	2006 Mar	16495264
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	17004721
Discovery of the HCV NS3/4A protease inhibitor (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) II. Key steps in structure-based optimization.	2007 May 17	17444623
Preclinical characteristics of the hepatitis C virus NS3/4A protease inhibitor ITMN-191 (R7227).	2008 Dec	18824605
Inhibitors of hepatitis C virus NS3/4A: alpha-ketoamide based macrocyclic inhibitors.	2009 Apr 15	19285390
Discovery and structure-activity relationship of P1-P3 ketoamide derived macrocyclic inhibitors of hepatitis C virus NS3 protease.	2009 Jan 22	19102654
Substituted imidazopyridines as potent inhibitors of HCV replication.	2009 May	19303654
Advances in the development of macrocyclic inhibitors of hepatitis C virus NS3-4A protease.	2010	20536420
Cyclic sulfones as novel P3-caps for hepatitis C virus NS3/4A (HCV NS3/4A) protease inhibitors: synthesis and evaluation of inhibitors with improved potency and pharmacokinetic profiles.	2010 Apr 22	20302300
Hepatitis C Virus NS3/4A Protease Inhibitors: A Light at the End of the Tunnel.	2010 Aug	21994705
Comparison of the Mechanisms of Drug Resistance among HIV, Hepatitis B, and Hepatitis C.	2010 Dec 1	21243082
Activity of aminocandin (IP960; HMR3270) compared with amphotericin B, itraconazole, caspofungin and micafungin in neutropenic murine models of disseminated infection caused by itraconazole-susceptible and -resistant strains of Aspergillus fumigatus.	2010 Feb	20015618
MK-7009, a potent and selective inhibitor of hepatitis C virus NS3/4A protease.	2010 Jan	19841155
The hepatitis C virus (HCV) NS4B RNA binding inhibitor clemizole is highly synergistic with HCV protease inhibitors.	2010 Jul 1	20486856
Improved P2 phenylglycine-based hepatitis C virus NS3 protease inhibitors with alkenylic prime-side substituents.	2010 Jul 15	20541424
Discovery of potent sulfonamide P4-capped ketoamide second generation inhibitors of hepatitis C virus NS3 serine protease with favorable pharmacokinetic profiles in preclinical species.	2010 Mar 1	20149666
Preclinical characterization of BI 201335, a C-terminal carboxylic acid inhibitor of the hepatitis C virus NS3-NS4A protease.	2010 Nov	20823284
Estimation of inhibitory quotient using a comparative equilibrium dialysis assay for prediction of viral response to hepatitis C virus inhibitors.	2011 May	20456634
Differential efficacy of protease inhibitors against HCV genotypes 2a, 3a, 5a, and 6a NS3/4A protease recombinant viruses.	2011 Sep	21699793
Review of boceprevir and telaprevir for the treatment of chronic hepatitis C.	2012 Apr	22506260
Single-dose pharmacokinetics of boceprevir in subjects with impaired hepatic or renal function.	2012 Sep 1	22799589
Direct-acting antiviral agents for hepatitis C virus infection.	2013	23140245
Azetidines and spiro azetidines as novel P2 units in hepatitis C virus NS3 protease inhibitors.	2013 Dec 1	24135727
Primuline derivatives that mimic RNA to stimulate hepatitis C virus NS3 helicase-catalyzed ATP hydrolysis.	2013 Jul 5	23703611
Analogs design, synthesis and biological evaluation of peptidomimetics with potential anti-HCV activity.	2013 May 15	23583031
In vitro efficacy of approved and experimental antivirals against novel genotype 3 hepatitis C virus subgenomic replicons.	2013 Nov	24013001
Restoration of the activated Rig-I pathway in hepatitis C virus (HCV) replicon cells by HCV protease, polymerase, and NS5A inhibitors in vitro at clinically relevant concentrations.	2013 Sep	23836176
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	23913364
The combination of alisporivir plus an NS5A inhibitor provides additive to synergistic anti-hepatitis C virus activity without detectable cross-resistance.	2014 Jun	24687498

Patents

Sample Use Guides

In Vivo Use Guide

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

In Vitro Use Guide

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

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)