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

Details

Stereochemistry ABSOLUTE
Molecular Formula C36H53N7O6
Molecular Weight 679.8493
Optical Activity UNSPECIFIED
Defined Stereocenters 6 / 6
E/Z Centers 0
Charge 0

SHOW SMILES / InChI
Structure of TELAPREVIR

SMILES

[H][C@@]12CCC[C@]1([H])[C@H](N(C2)C(=O)[C@@H](NC(=O)[C@@H](NC(=O)C3=CN=CC=N3)C4CCCCC4)C(C)(C)C)C(=O)N[C@@H](CCC)C(=O)C(=O)NC5CC5

InChI

InChIKey=BBAWEDCPNXPBQM-GDEBMMAJSA-N
InChI=1S/C36H53N7O6/c1-5-10-25(29(44)34(48)39-23-15-16-23)40-33(47)28-24-14-9-13-22(24)20-43(28)35(49)30(36(2,3)4)42-32(46)27(21-11-7-6-8-12-21)41-31(45)26-19-37-17-18-38-26/h17-19,21-25,27-28,30H,5-16,20H2,1-4H3,(H,39,48)(H,40,47)(H,41,45)(H,42,46)/t22-,24-,25-,27-,28-,30+/m0/s1

HIDE SMILES / InChI
Molecular Formula C36H53N7O6
Molecular Weight 679.8493
Charge 0
Count
Stereochemistry ABSOLUTE
Additional Stereochemistry No
Defined Stereocenters 6 / 6
E/Z Centers 0
Optical Activity UNSPECIFIED

Description
Curator's Comment: description was created based on several sources, including http://www.millionpharma.com/telaprevir.php; https://www.jnj.com/media-center/press-releases/incivo-telaprevir-approved-in-europe-offering-higher-cure-rates-for-genotype-1-chronic-hepatitis-c-compared-to-standard-treatment

Telaprevir (marketed under the brand names Incivek and Incivo) is a direct-acting antiviralagent against the hepatitis C virus (HCV). It is a hepatitis C virus NS3/4A protease inhibitor indicated for the treatment of genotype 1 chronic hepatitis C (CHC) in adult patients with compensated liver disease, including cirrhosis, who are treatment-naïve or who have been previously treated with interferon-based treatment, including prior null responders, partial responders, and relapsers in combination with peginterferon alfa and ribavirin. Telaprevir is not used as a monotherapy. It is necessary for the proteolytic cleavage of the HCV encoded polyprotein into mature forms of the NS4A, NS4B, NS5A and NS5B proteins and essential for viral replication. It belongs to the chemical class of alpha-ketoamids and binds to NS3/4A in a covalent but reversible manner.

Originator

Janssen Pharmaceutica|Vertex|Mitsubishi Tanabe Pharma
1
Curator's Comment: The Janssen Companies have the right to commercialize telaprevir in Europe, Latin America, the Middle East, Africa, India, Australia and New Zealand under the commercial name INCIVO®; Vertex has the right to commercialize telaprevir in North America under the name INCIVEK™ (approved by US FDA in May 2011 and by Health Canada in August 2011 for genotype-1 chronic hepatitis C with compensated liver disease); Mitsubishi Tanabe Pharma has the right to commercialize telaprevir in Japan and certain Far Eastern countries. # Tibotec (Janssen Pharmaceutical Companies) in collaboration with Vertex and Mitsubishi Tanabe Pharma

Approval Year

2011
587
Targets

Targets

Primary TargetPharmacologyConditionPotency
Inhibitor
8297
 10.0 nM [IC50]
Conditions

Conditions

ConditionModalityTargetsHighest PhaseProduct
Curative
Approved
8429
INCIVEK

Approved Use

Indicated, in combination with peginterferon alfa and ribavirin, for the treatment of genotype 1 chronic hepatitis C (CHC) in adult patients with compensated liver disease, including cirrhosis, who are treatment-naïve or who have been previously treated with interferon-based treatment, including prior null responders, partial responders, and relapsers. Incivek must not be used as monotherapy and must only be used in combination with peginterferon alfa and ribavirin.

Launch Date

2011
Cmax

Cmax

ValueDoseCo-administeredAnalytePopulation
1940 ng/mL
OTHER GOV
https://www.accessdata.fda.gov/drugsatfda_docs/nda/2011/201917Orig1s000ClinPharmR.pdf
750 mg 3 times / day steady-state, oral
dose: 750 mg
route of administration: Oral
experiment type: STEADY-STATE
co-administered:
VRT-127394 plasma
Homo sapiens
population: HEALTHY
age: ADULT
sex: UNKNOWN
food status: UNKNOWN
511 ng/mL
OTHER GOV
https://www.accessdata.fda.gov/drugsatfda_docs/nda/2011/201917Orig1s000ClinPharmR.pdf
750 mg single, oral
dose: 750 mg
route of administration: Oral
experiment type: SINGLE
co-administered:
VRT-127394 plasma
Homo sapiens
population: HEALTHY
age: ADULT
sex: UNKNOWN
food status: FED
3090 ng/mL
OTHER GOV
https://www.accessdata.fda.gov/drugsatfda_docs/nda/2011/201917Orig1s000ClinPharmR.pdf
750 mg 3 times / day steady-state, oral
dose: 750 mg
route of administration: Oral
experiment type: STEADY-STATE
co-administered:
TELAPREVIR plasma
Homo sapiens
population: HEALTHY
age: ADULT
sex: UNKNOWN
food status: UNKNOWN
1740.84 ng/mL
OTHER GOV
https://www.accessdata.fda.gov/drugsatfda_docs/nda/2011/201917Orig1s000ClinPharmR.pdf
750 mg single, oral
dose: 750 mg
route of administration: Oral
experiment type: SINGLE
co-administered:
TELAPREVIR plasma
Homo sapiens
population: HEALTHY
age: ADULT
sex: UNKNOWN
food status: FED
3232.22 ng/mL
OTHER GOV
https://www.accessdata.fda.gov/drugsatfda_docs/nda/2011/201917Orig1s000ClinPharmR.pdf
1500 mg single, oral
dose: 1500 mg
route of administration: Oral
experiment type: SINGLE
co-administered:
TELAPREVIR plasma
Homo sapiens
population: HEALTHY
age: ADULT
sex: UNKNOWN
food status: FED
539.79 ng/mL
OTHER GOV
https://www.accessdata.fda.gov/drugsatfda_docs/nda/2011/201917Orig1s000ClinPharmR.pdf
375 mg single, oral
dose: 375 mg
route of administration: Oral
experiment type: SINGLE
co-administered:
TELAPREVIR plasma
Homo sapiens
population: HEALTHY
age: ADULT
sex: UNKNOWN
food status: FED
AUC

AUC

ValueDoseCo-administeredAnalytePopulation
13274.77 ng × h/mL
OTHER GOV
https://www.accessdata.fda.gov/drugsatfda_docs/nda/2011/201917Orig1s000ClinPharmR.pdf
750 mg 3 times / day steady-state, oral
dose: 750 mg
route of administration: Oral
experiment type: STEADY-STATE
co-administered:
VRT-127394 plasma
Homo sapiens
population: HEALTHY
age: ADULT
sex: UNKNOWN
food status: UNKNOWN
5203 ng × h/mL
OTHER GOV
https://www.accessdata.fda.gov/drugsatfda_docs/nda/2011/201917Orig1s000ClinPharmR.pdf
750 mg single, oral
dose: 750 mg
route of administration: Oral
experiment type: SINGLE
co-administered:
VRT-127394 plasma
Homo sapiens
population: HEALTHY
age: ADULT
sex: UNKNOWN
food status: FED
19809.27 ng × h/mL
OTHER GOV
https://www.accessdata.fda.gov/drugsatfda_docs/nda/2011/201917Orig1s000ClinPharmR.pdf
750 mg 3 times / day steady-state, oral
dose: 750 mg
route of administration: Oral
experiment type: STEADY-STATE
co-administered:
TELAPREVIR plasma
Homo sapiens
population: HEALTHY
age: ADULT
sex: UNKNOWN
food status: UNKNOWN
11749.1 ng × h/mL
OTHER GOV
https://www.accessdata.fda.gov/drugsatfda_docs/nda/2011/201917Orig1s000ClinPharmR.pdf
750 mg single, oral
dose: 750 mg
route of administration: Oral
experiment type: SINGLE
co-administered:
TELAPREVIR plasma
Homo sapiens
population: HEALTHY
age: ADULT
sex: UNKNOWN
food status: FED
24250.23 ng × h/mL
OTHER GOV
https://www.accessdata.fda.gov/drugsatfda_docs/nda/2011/201917Orig1s000ClinPharmR.pdf
1500 mg single, oral
dose: 1500 mg
route of administration: Oral
experiment type: SINGLE
co-administered:
TELAPREVIR plasma
Homo sapiens
population: HEALTHY
age: ADULT
sex: UNKNOWN
food status: FED
3146.52 ng × h/mL
OTHER GOV
https://www.accessdata.fda.gov/drugsatfda_docs/nda/2011/201917Orig1s000ClinPharmR.pdf
375 mg single, oral
dose: 375 mg
route of administration: Oral
experiment type: SINGLE
co-administered:
TELAPREVIR plasma
Homo sapiens
population: HEALTHY
age: ADULT
sex: UNKNOWN
food status: FED
T1/2

T1/2

ValueDoseCo-administeredAnalytePopulation
4.77 h
OTHER GOV
https://www.accessdata.fda.gov/drugsatfda_docs/nda/2011/201917Orig1s000ClinPharmR.pdf
750 mg single, oral
dose: 750 mg
route of administration: Oral
experiment type: SINGLE
co-administered:
VRT-127394 plasma
Homo sapiens
population: HEALTHY
age: ADULT
sex: UNKNOWN
food status: FED
3.96 h
OTHER GOV
https://www.accessdata.fda.gov/drugsatfda_docs/nda/2011/201917Orig1s000ClinPharmR.pdf
750 mg single, oral
dose: 750 mg
route of administration: Oral
experiment type: SINGLE
co-administered:
TELAPREVIR plasma
Homo sapiens
population: HEALTHY
age: ADULT
sex: UNKNOWN
food status: FED
6.49 h
OTHER GOV
https://www.accessdata.fda.gov/drugsatfda_docs/nda/2011/201917Orig1s000ClinPharmR.pdf
1500 mg single, oral
dose: 1500 mg
route of administration: Oral
experiment type: SINGLE
co-administered:
TELAPREVIR plasma
Homo sapiens
population: HEALTHY
age: ADULT
sex: UNKNOWN
food status: FED
3.23 h
OTHER GOV
https://www.accessdata.fda.gov/drugsatfda_docs/nda/2011/201917Orig1s000ClinPharmR.pdf
375 mg single, oral
dose: 375 mg
route of administration: Oral
experiment type: SINGLE
co-administered:
TELAPREVIR plasma
Homo sapiens
population: HEALTHY
age: ADULT
sex: UNKNOWN
food status: FED
Funbound

Funbound

ValueDoseCo-administeredAnalytePopulation
32.5%
OTHER GOV
https://www.accessdata.fda.gov/drugsatfda_docs/nda/2011/201917Orig1s000ClinPharmR.pdf
375 mg single, oral
dose: 375 mg
route of administration: Oral
experiment type: SINGLE
co-administered:
TELAPREVIR plasma
Homo sapiens
population: HEALTHY
age: ADULT
sex: UNKNOWN
food status: FED
Doses

Doses

DosePopulationAdverse events​
750 mg 3 times / day multiple, oral
Recommended
Dose: 750 mg, 3 times / day
Route: oral
Route: multiple
Dose: 750 mg, 3 times / day
Co-administed with::
peginterferon alfa
ribavirin
Sources:
https://pubmed.ncbi.nlm.nih.gov/30566559
unhealthy, 58 years
n = 1
Health Status: unhealthy
Condition: chronic hepatitis C virus
Age Group: 58 years
Sex: F
Population Size: 1
Sources:
https://pubmed.ncbi.nlm.nih.gov/30566559
Disc. AE: DRESS syndrome...
AEs leading to
discontinuation/dose reduction:
DRESS syndrome (1 patient)
Sources:
https://pubmed.ncbi.nlm.nih.gov/30566559
1875 mg 3 times / day multiple, oral
Highest studied dose
Dose: 1875 mg, 3 times / day
Route: oral
Route: multiple
Dose: 1875 mg, 3 times / day
Sources:
https://www.accessdata.fda.gov/drugsatfda_docs/label/2011/201917lbl.pdf
healthy, adult
Health Status: healthy
Age Group: adult
Sources:
https://www.accessdata.fda.gov/drugsatfda_docs/label/2011/201917lbl.pdf
Other AEs: Nausea, Headache...
Other AEs:
Nausea
Headache
Diarrhea
Decreased appetite
Dysgeusia
Vomiting
Sources:
https://www.accessdata.fda.gov/drugsatfda_docs/label/2011/201917lbl.pdf
750 mg 3 times / day multiple, oral
Recommended
Dose: 750 mg, 3 times / day
Route: oral
Route: multiple
Dose: 750 mg, 3 times / day
Co-administed with::
peginterferon alfa
ribavirin
Sources:
https://www.accessdata.fda.gov/drugsatfda_docs/nda/2011/201917Orig1s000MedR.pdf
Page: p. 68
unhealthy, adult
n = 1797
Health Status: unhealthy
Age Group: adult
Population Size: 1797
Sources:
https://www.accessdata.fda.gov/drugsatfda_docs/nda/2011/201917Orig1s000MedR.pdf
Page: p. 68
Disc. AE: Anemia, Skin disorder...
AEs leading to
discontinuation/dose reduction:
Anemia (22%)
Skin disorder (20%)
Fatigue (6%)
Nausea (4%)
Vomiting (4%)
Sources:
https://www.accessdata.fda.gov/drugsatfda_docs/nda/2011/201917Orig1s000MedR.pdf
Page: p. 68
AEs

AEs

AESignificanceDosePopulation
DRESS syndrome 1 patient
Disc. AE
750 mg 3 times / day multiple, oral
Recommended
Dose: 750 mg, 3 times / day
Route: oral
Route: multiple
Dose: 750 mg, 3 times / day
Co-administed with::
peginterferon alfa
ribavirin
Sources:
https://pubmed.ncbi.nlm.nih.gov/30566559
unhealthy, 58 years
n = 1
Health Status: unhealthy
Condition: chronic hepatitis C virus
Age Group: 58 years
Sex: F
Population Size: 1
Sources:
https://pubmed.ncbi.nlm.nih.gov/30566559
Decreased appetite
1875 mg 3 times / day multiple, oral
Highest studied dose
Dose: 1875 mg, 3 times / day
Route: oral
Route: multiple
Dose: 1875 mg, 3 times / day
Sources:
https://www.accessdata.fda.gov/drugsatfda_docs/label/2011/201917lbl.pdf
healthy, adult
Health Status: healthy
Age Group: adult
Sources:
https://www.accessdata.fda.gov/drugsatfda_docs/label/2011/201917lbl.pdf
Diarrhea
1875 mg 3 times / day multiple, oral
Highest studied dose
Dose: 1875 mg, 3 times / day
Route: oral
Route: multiple
Dose: 1875 mg, 3 times / day
Sources:
https://www.accessdata.fda.gov/drugsatfda_docs/label/2011/201917lbl.pdf
healthy, adult
Health Status: healthy
Age Group: adult
Sources:
https://www.accessdata.fda.gov/drugsatfda_docs/label/2011/201917lbl.pdf
Dysgeusia
1875 mg 3 times / day multiple, oral
Highest studied dose
Dose: 1875 mg, 3 times / day
Route: oral
Route: multiple
Dose: 1875 mg, 3 times / day
Sources:
https://www.accessdata.fda.gov/drugsatfda_docs/label/2011/201917lbl.pdf
healthy, adult
Health Status: healthy
Age Group: adult
Sources:
https://www.accessdata.fda.gov/drugsatfda_docs/label/2011/201917lbl.pdf
Headache
1875 mg 3 times / day multiple, oral
Highest studied dose
Dose: 1875 mg, 3 times / day
Route: oral
Route: multiple
Dose: 1875 mg, 3 times / day
Sources:
https://www.accessdata.fda.gov/drugsatfda_docs/label/2011/201917lbl.pdf
healthy, adult
Health Status: healthy
Age Group: adult
Sources:
https://www.accessdata.fda.gov/drugsatfda_docs/label/2011/201917lbl.pdf
Nausea
1875 mg 3 times / day multiple, oral
Highest studied dose
Dose: 1875 mg, 3 times / day
Route: oral
Route: multiple
Dose: 1875 mg, 3 times / day
Sources:
https://www.accessdata.fda.gov/drugsatfda_docs/label/2011/201917lbl.pdf
healthy, adult
Health Status: healthy
Age Group: adult
Sources:
https://www.accessdata.fda.gov/drugsatfda_docs/label/2011/201917lbl.pdf
Vomiting
1875 mg 3 times / day multiple, oral
Highest studied dose
Dose: 1875 mg, 3 times / day
Route: oral
Route: multiple
Dose: 1875 mg, 3 times / day
Sources:
https://www.accessdata.fda.gov/drugsatfda_docs/label/2011/201917lbl.pdf
healthy, adult
Health Status: healthy
Age Group: adult
Sources:
https://www.accessdata.fda.gov/drugsatfda_docs/label/2011/201917lbl.pdf
Skin disorder 20%
Disc. AE
750 mg 3 times / day multiple, oral
Recommended
Dose: 750 mg, 3 times / day
Route: oral
Route: multiple
Dose: 750 mg, 3 times / day
Co-administed with::
peginterferon alfa
ribavirin
Sources:
https://www.accessdata.fda.gov/drugsatfda_docs/nda/2011/201917Orig1s000MedR.pdf
Page: p. 68
unhealthy, adult
n = 1797
Health Status: unhealthy
Age Group: adult
Population Size: 1797
Sources:
https://www.accessdata.fda.gov/drugsatfda_docs/nda/2011/201917Orig1s000MedR.pdf
Page: p. 68
Anemia 22%
Disc. AE
750 mg 3 times / day multiple, oral
Recommended
Dose: 750 mg, 3 times / day
Route: oral
Route: multiple
Dose: 750 mg, 3 times / day
Co-administed with::
peginterferon alfa
ribavirin
Sources:
https://www.accessdata.fda.gov/drugsatfda_docs/nda/2011/201917Orig1s000MedR.pdf
Page: p. 68
unhealthy, adult
n = 1797
Health Status: unhealthy
Age Group: adult
Population Size: 1797
Sources:
https://www.accessdata.fda.gov/drugsatfda_docs/nda/2011/201917Orig1s000MedR.pdf
Page: p. 68
Nausea 4%
Disc. AE
750 mg 3 times / day multiple, oral
Recommended
Dose: 750 mg, 3 times / day
Route: oral
Route: multiple
Dose: 750 mg, 3 times / day
Co-administed with::
peginterferon alfa
ribavirin
Sources:
https://www.accessdata.fda.gov/drugsatfda_docs/nda/2011/201917Orig1s000MedR.pdf
Page: p. 68
unhealthy, adult
n = 1797
Health Status: unhealthy
Age Group: adult
Population Size: 1797
Sources:
https://www.accessdata.fda.gov/drugsatfda_docs/nda/2011/201917Orig1s000MedR.pdf
Page: p. 68
Vomiting 4%
Disc. AE
750 mg 3 times / day multiple, oral
Recommended
Dose: 750 mg, 3 times / day
Route: oral
Route: multiple
Dose: 750 mg, 3 times / day
Co-administed with::
peginterferon alfa
ribavirin
Sources:
https://www.accessdata.fda.gov/drugsatfda_docs/nda/2011/201917Orig1s000MedR.pdf
Page: p. 68
unhealthy, adult
n = 1797
Health Status: unhealthy
Age Group: adult
Population Size: 1797
Sources:
https://www.accessdata.fda.gov/drugsatfda_docs/nda/2011/201917Orig1s000MedR.pdf
Page: p. 68
Fatigue 6%
Disc. AE
750 mg 3 times / day multiple, oral
Recommended
Dose: 750 mg, 3 times / day
Route: oral
Route: multiple
Dose: 750 mg, 3 times / day
Co-administed with::
peginterferon alfa
ribavirin
Sources:
https://www.accessdata.fda.gov/drugsatfda_docs/nda/2011/201917Orig1s000MedR.pdf
Page: p. 68
unhealthy, adult
n = 1797
Health Status: unhealthy
Age Group: adult
Population Size: 1797
Sources:
https://www.accessdata.fda.gov/drugsatfda_docs/nda/2011/201917Orig1s000MedR.pdf
Page: p. 68
Overview

Overview

CYP3A4CYP2C9CYP2D6hERG
substrate
1737

inhibitor
1587
substrate
1037

inhibitor
1767
substrate
1217

inhibitor
1852
inhibitor
1612

OverviewOther

Other InhibitorOther SubstrateOther Inducer
CYP1A2
1524

CYP2A6
707

CYP2B6
810

CYP2C8
911

CYP2C19
1478

CYP2E1
882

P-gp
1461

UGT1A1
204

OATP1B1
788
CYP1A2
1054

CYP2C19
991

CYP2E1
667

P-gp
1537
CYP1A
56

CYP2C19
293

CYP3A
129
Drug as perpetrator​

Drug as perpetrator​

TargetModalityActivityMetaboliteClinical evidence
CYP1A
121
 likely
UGT1A1
254
 no
P-gp
1650
 no
yes (co-administration study)
Comment: telaprevir caused a nearly 2-fold increase in exposure (Cmax, AUClast) to digoxin. Clearance of digoxin was decreased by 46% in the presence of telaprevir
Page: 50.0
CYP2C19
1553
 unlikely
CYP3A
298
 unlikely
OATP1B1
803
 unlikely
CYP1A2
1692
 weak [IC50 >100 uM]
CYP2A6
739
 weak [IC50 >100 uM]
CYP2B6
1001
 weak [IC50 >100 uM]
CYP2C19
1553
 weak [IC50 >100 uM]
CYP2C8
965
 weak [IC50 >100 uM]
CYP2C9
1819
 weak [IC50 >100 uM]
CYP2D6
1891
 weak [IC50 >100 uM]
CYP2E1
970
 weak [IC50 >100 uM]
CYP3A4
1925
 yes [IC50 2.8 uM]
weak (co-administration study)
Comment: 21 days of dosing with Modicon (0.5 mg NE + 0.035 mg EE) and telaprevir resulted in a decrease in EE plasma concentrations: Mean EE Cmax, Cmin, and AUCss were decreased by 26%, 32%, and 27%, respectively. Telaprevir also decreased NE exposure: mean NE Cmax, Cmin, and AUCss were decreased by 16%, 7%, and 10%, respectively
Page: 81.0
Drug as victim

Drug as victim

TargetModalityActivityMetaboliteClinical evidence
CYP3A4
1737
 major
yes (co-administration study)
Comment: mean telaprevir AUCinf and mean AUC0-24h values were approximately 67% higher and mean telaprevir Cmax values were approximately 29% higher in subjects receiving telaprevir+ketoconazole; rifampin causes a significant increase in CYP3A4 metabolism resulting in a greater than 10-fold decrease in telaprevir AUClast exposure and 7-fold decrease in Cmax; Lopinavir/ritonavir (CYP3A4/P-gp inhibitors) significantly lowers telaprevir exposure (54% decrease in AUCτ and 55% decrease in Cmax) and could result in subtherapeutic concentrations of telaprevir
Page: 48.0
CYP1A2
1054
 no
CYP2C19
991
 no
CYP2C9
1037
 no
CYP2D6
1217
 no
CYP2E1
667
 no
P-gp
1537
 yes
yes (co-administration study)
Comment: Lopinavir/ritonavir (CYP3A4/P-gp inhibitors) significantly lowers telaprevir exposure (54% decrease in AUCτ and 55% decrease in Cmax) and could result in subtherapeutic concentrations of telaprevir
Page: 49.0
Tox targets

Tox targets

TargetModalityActivityMetaboliteClinical evidence
hERG
1647
Sourcing

Sourcing

Vendor/AggregatorIDURL
ChEBI
CHEBI:68595
https://www.ebi.ac.uk/chebi/searchId.do?chebiId=CHEBI:68595
ChemicalBook
CB41519837
https://www.chemicalbook.com/ChemicalProductProperty_EN_CB41519837
MolPort
MolPort-006-170-103
https://www.molport.com/shop/molecule-link/MolPort-006-170-103
ZINC
ZINC000003992480
http://zinc15.docking.org/substances/ZINC000003992480
eMolecules
36759428
https://www.emolecules.com/cgi-bin/more?vid=36759428
eMolecules
36762442
https://www.emolecules.com/cgi-bin/more?vid=36762442
PubMed

PubMed

TitleDatePubMed
Non-HIV antivirals - a review of the recent patent literature.
2002 Aug
In vitro resistance studies of hepatitis C virus serine protease inhibitors, VX-950 and BILN 2061: structural analysis indicates different resistance mechanisms.
2004 Apr 23
P4 and P1' optimization of bicycloproline P2 bearing tetrapeptidyl alpha-ketoamides as HCV protease inhibitors.
2004 Oct 4
Discovery of small-molecule inhibitors of HCV NS3-4A protease as potential therapeutic agents against HCV infection.
2005
In vitro studies of cross-resistance mutations against two hepatitis C virus serine protease inhibitors, VX-950 and BILN 2061.
2005 Nov 4
VX-950, a novel hepatitis C virus (HCV) NS3-4A protease inhibitor, exhibits potent antiviral activities in HCv replicon cells.
2006 May
Preclinical characteristics of the hepatitis C virus NS3/4A protease inhibitor ITMN-191 (R7227).
2008 Dec
The hepatitis C virus replicon presents a higher barrier to resistance to nucleoside analogs than to nonnucleoside polymerase or protease inhibitors.
2008 May
In vitro and in vivo isotope effects with hepatitis C protease inhibitors: enhanced plasma exposure of deuterated telaprevir versus telaprevir in rats.
2009 Dec 24
Substituted imidazopyridines as potent inhibitors of HCV replication.
2009 May
Synthesis of potent antitumor and antiviral benzofuran derivatives.
2009 May 1
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
MK-7009, a potent and selective inhibitor of hepatitis C virus NS3/4A protease.
2010 Jan
The hepatitis C virus (HCV) NS4B RNA binding inhibitor clemizole is highly synergistic with HCV protease inhibitors.
2010 Jul 1
Elimination of hepatitis C virus by short term NS3-4A and NS5B inhibitor combination therapy in human hepatocyte chimeric mice.
2011 May
Azetidines and spiro azetidines as novel P2 units in hepatitis C virus NS3 protease inhibitors.
2013 Dec 1
In vitro efficacy of approved and experimental antivirals against novel genotype 3 hepatitis C virus subgenomic replicons.
2013 Nov
Synthesis and antiviral activity of a novel class of (5-oxazolyl)phenyl amines.
2013 Nov
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
Inhibition of hepatitis C virus replication by GS-6620, a potent C-nucleoside monophosphate prodrug.
2014
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
Rhabdomyolysis in a hepatitis C virus infected patient treated with telaprevir and simvastatin.
2014 Jul-Aug
Hepatitis C virus: Virology, diagnosis and treatment.
2015 Jun 8
Systems pharmacological analysis of drugs inducing stevens-johnson syndrome and toxic epidermal necrolysis.
2015 May 18
Patents

Patents

08383858
1
08399615
1

Sample Use Guides

In Vivo Use Guide
1125 mg taken twice daily (10-14 hours apart) with food (not low fat). Incivek must be administered with both peginterferon alfa and ribavirin for all patients for 12 weeks, followed by a response-guided regimen of either 12 or 36 additional weeks of peginterferon alfa and ribavirin depending on viral response and prior response status.
Route of Administration: Oral
In Vitro Use Guide
Telaprevir demonstrated excellent antiviral activity both in genotype 1b HCV replicon cells with the IC50 of 354 nM and in human fetal hepatocytes infected with genotype 1a HCV-positive patient sera (IC50 = 280 nM).
Substance Class Chemical
Created
by admin
on Fri Dec 15 16:04:26 GMT 2023
Edited
by admin
on Fri Dec 15 16:04:26 GMT 2023
Record UNII
655M5O3W0U
Record Status Validated (UNII)
Record Version
  • Download
Name Type Language
TELAPREVIR
DASH   INN   JAN   MART.   MI   ORANGE BOOK   USAN   VANDF   WHO-DD  
USAN   INN  
Official Name English
Telaprevir [WHO-DD]
Common Name English
VRT-111950
Code English
VX-950
Code English
TELAPREVIR [JAN]
Common Name English
LY 570310
Code English
INCIVO
Brand Name English
VRT 111950
Code English
telaprevir [INN]
Common Name English
(1S,3aR,6aS)-2-[(2S)-2-[[(2S)-Cyclohexyl[(pyrazinylcarbonyl)amino]acetyl]amino]-3,3-dimethylbutanoyl]-N-[(1S)-1-[(cyclopropylamino)oxoacetyl]butyl] octahydrocyclopenta[c]pyrrole-1-carboxamide
Common Name English
TELAPREVIR [ORANGE BOOK]
Common Name English
TELAPREVIR [USAN]
Common Name English
LY-570310
Code English
MP 424
Code English
INCIVEK
Brand Name English
TELAPREVIR [VANDF]
Common Name English
CYCLOPENTA(C)PYRROLE-1-CARBOXAMIDE, (2S)-2-CYCLOHEXYL-N-(PYRAZINYLCARBONYL)GLYCYL-3-METHYL-L-VALYL-N-((1S)-1-((CYCLOPROPYLAMINO)OXOACETYL)BUTYL)OCTAHYDRO-, (1S,3AR,6AS)-
Common Name English
VX 950
Code English
MP-424
Code English
TELAPREVIR [MI]
Common Name English
TELAPREVIR [MART.]
Common Name English
Classification Tree Code System Code
WHO-VATC QJ05AE11
Created by admin on Fri Dec 15 16:04:26 GMT 2023 , Edited by admin on Fri Dec 15 16:04:26 GMT 2023
EMA ASSESSMENT REPORTS INCIVO (AUTHORIZED: HEPATITIS C, CHRONIC)
Created by admin on Fri Dec 15 16:04:26 GMT 2023 , Edited by admin on Fri Dec 15 16:04:26 GMT 2023
NDF-RT N0000182639
Created by admin on Fri Dec 15 16:04:26 GMT 2023 , Edited by admin on Fri Dec 15 16:04:26 GMT 2023
NCI_THESAURUS C783
Created by admin on Fri Dec 15 16:04:26 GMT 2023 , Edited by admin on Fri Dec 15 16:04:26 GMT 2023
LIVERTOX NBK548138
Created by admin on Fri Dec 15 16:04:26 GMT 2023 , Edited by admin on Fri Dec 15 16:04:26 GMT 2023
NCI_THESAURUS C281
Created by admin on Fri Dec 15 16:04:26 GMT 2023 , Edited by admin on Fri Dec 15 16:04:26 GMT 2023
WHO-ATC J05AP02
Created by admin on Fri Dec 15 16:04:26 GMT 2023 , Edited by admin on Fri Dec 15 16:04:26 GMT 2023
WHO-ATC J05AE11
Created by admin on Fri Dec 15 16:04:26 GMT 2023 , Edited by admin on Fri Dec 15 16:04:26 GMT 2023
Code System Code Type Description
FDA UNII
655M5O3W0U
Created by admin on Fri Dec 15 16:04:26 GMT 2023 , Edited by admin on Fri Dec 15 16:04:26 GMT 2023
PRIMARY
HSDB
8125
Created by admin on Fri Dec 15 16:04:26 GMT 2023 , Edited by admin on Fri Dec 15 16:04:26 GMT 2023
PRIMARY
USAN
SS-135
Created by admin on Fri Dec 15 16:04:26 GMT 2023 , Edited by admin on Fri Dec 15 16:04:26 GMT 2023
PRIMARY
CAS
402957-28-2
Created by admin on Fri Dec 15 16:04:26 GMT 2023 , Edited by admin on Fri Dec 15 16:04:26 GMT 2023
PRIMARY
MESH
C486464
Created by admin on Fri Dec 15 16:04:26 GMT 2023 , Edited by admin on Fri Dec 15 16:04:26 GMT 2023
PRIMARY
NDF-RT
N0000190114
Created by admin on Fri Dec 15 16:04:26 GMT 2023 , Edited by admin on Fri Dec 15 16:04:26 GMT 2023
PRIMARY Cytochrome P450 3A Inhibitors [MoA]
NDF-RT
N0000190109
Created by admin on Fri Dec 15 16:04:26 GMT 2023 , Edited by admin on Fri Dec 15 16:04:26 GMT 2023
PRIMARY Organic Anion Transporting Polypeptide 2B1 Inhibitors [MoA]
EVMPD
SUB31651
Created by admin on Fri Dec 15 16:04:26 GMT 2023 , Edited by admin on Fri Dec 15 16:04:26 GMT 2023
PRIMARY
NDF-RT
N0000182638
Created by admin on Fri Dec 15 16:04:26 GMT 2023 , Edited by admin on Fri Dec 15 16:04:26 GMT 2023
PRIMARY HCV NS3/4A Protease Inhibitors [MoA]
DRUG BANK
DB05521
Created by admin on Fri Dec 15 16:04:26 GMT 2023 , Edited by admin on Fri Dec 15 16:04:26 GMT 2023
PRIMARY
DRUG CENTRAL
4173
Created by admin on Fri Dec 15 16:04:26 GMT 2023 , Edited by admin on Fri Dec 15 16:04:26 GMT 2023
PRIMARY
INN
8686
Created by admin on Fri Dec 15 16:04:26 GMT 2023 , Edited by admin on Fri Dec 15 16:04:26 GMT 2023
PRIMARY
NCI_THESAURUS
C81603
Created by admin on Fri Dec 15 16:04:26 GMT 2023 , Edited by admin on Fri Dec 15 16:04:26 GMT 2023
PRIMARY
EPA CompTox
DTXSID40193304
Created by admin on Fri Dec 15 16:04:26 GMT 2023 , Edited by admin on Fri Dec 15 16:04:26 GMT 2023
PRIMARY
PUBCHEM
3010818
Created by admin on Fri Dec 15 16:04:26 GMT 2023 , Edited by admin on Fri Dec 15 16:04:26 GMT 2023
PRIMARY
CHEBI
68595
Created by admin on Fri Dec 15 16:04:26 GMT 2023 , Edited by admin on Fri Dec 15 16:04:26 GMT 2023
PRIMARY
LACTMED
Telaprevir
Created by admin on Fri Dec 15 16:04:26 GMT 2023 , Edited by admin on Fri Dec 15 16:04:26 GMT 2023
PRIMARY
SMS_ID
100000124179
Created by admin on Fri Dec 15 16:04:26 GMT 2023 , Edited by admin on Fri Dec 15 16:04:26 GMT 2023
PRIMARY
RXCUI
1102261
Created by admin on Fri Dec 15 16:04:26 GMT 2023 , Edited by admin on Fri Dec 15 16:04:26 GMT 2023
PRIMARY RxNorm
NDF-RT
N0000185503
Created by admin on Fri Dec 15 16:04:26 GMT 2023 , Edited by admin on Fri Dec 15 16:04:26 GMT 2023
PRIMARY P-Glycoprotein Inhibitors [MoA]
NDF-RT
N0000190107
Created by admin on Fri Dec 15 16:04:26 GMT 2023 , Edited by admin on Fri Dec 15 16:04:26 GMT 2023
PRIMARY Organic Anion Transporting Polypeptide 1B1 Inhibitors [MoA]
MERCK INDEX
m10526
Created by admin on Fri Dec 15 16:04:26 GMT 2023 , Edited by admin on Fri Dec 15 16:04:26 GMT 2023
PRIMARY Merck Index
ChEMBL
CHEMBL231813
Created by admin on Fri Dec 15 16:04:26 GMT 2023 , Edited by admin on Fri Dec 15 16:04:26 GMT 2023
PRIMARY
WIKIPEDIA
TELAPREVIR
Created by admin on Fri Dec 15 16:04:26 GMT 2023 , Edited by admin on Fri Dec 15 16:04:26 GMT 2023
PRIMARY
Related Record Type Details
CYTOCHROME P450 3A4
METABOLIC ENZYME -> SUBSTRATE
MAJOR
MULTIDRUG RESISTANCE PROTEIN 1
TRANSPORTER -> SUBSTRATE
Structure of TELAPREVIR
EXCRETED UNCHANGED
FECAL
PLASMA PROTEIN FRACTION (HUMAN)
BINDER->LIGAND
The protein binding is concentration dependent and decreases with increasing telaprevir concentrations at all concentrations of human serum albumin (HSA) and α-1-acid glycoprotein (AAG). In addition, protein binding of telaprevir is affected by the concentration of HSA and AAG.
BINDING
Related Record Type Details
Structure of TELAPREVIR, (.ALPHA.-KETOAMIDE BOND REDUCED)-
METABOLITE INACTIVE -> PARENT
Structure of VRT-127394
METABOLITE LESS ACTIVE -> PARENT
Approximately 30-fold less potent than telaprevir.
MAJOR
PLASMA
Structure of (3S,3AS,6AR)-2-((2S)-2-(((2S)-2-AMINO-2-CYCLOHEXYL-ACETYL)AMINO)-3,3-DIMETHYL-BUTANOYL)-N-((1S)-1-(2-(CYCLOPROPYLAMINO)-2-OXO-ACETYL)BUTYL)-3,3A,4,5,6,6A-HEXAHYDRO-1H-CYCLOPENTA(C)PYRROLE-3-CARBOXAMIDE
METABOLITE -> PARENT
Structure of PYRAZINOIC ACID
METABOLITE -> PARENT
Structure of (3S,3AS,6AR)-2-((2S)-2-(((2S)-2-CYCLOHEXYL-2-(PYRAZINE-2-CARBONYLAMINO)ACETYL)AMINO)-3,3-DIMETHYL-BUTANOYL)-3,3A,4,5,6,6A-HEXAHYDRO-1H-CYCLOPENTA(C)PYRROLE-3-CARBOXAMIDE
METABOLITE -> PARENT
Related Record Type Details
Structure of TELAPREVIR
ACTIVE MOIETY
Name Property Type Amount Referenced Substance Defining Parameters References
Biological Half-life PHARMACOKINETIC
Tmax PHARMACOKINETIC single dose

Volume of Distribution PHARMACOKINETIC
NIH
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HHS VULNERABILITY DISCLOSURE
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