TELAPREVIR

US Previously Marketed

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 Search

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

Description
Sources: http://www.accessdata.fda.gov/drugsatfda_docs/label/2013/201917s012lbl.pdf
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

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/2013/201917s012lbl.pdf	Inhibitor 8297		10.0 nM [IC50]

Conditions

Condition	Modality	Targets	Highest Phase	Product
Chronic hepatitis C 42 Sources: http://www.accessdata.fda.gov/drugsatfda_docs/label/2013/201917s012lbl.pdf	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

C_max

Value	Dose	Analyte	Population
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

Value	Dose	Analyte	Population
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

T_1/2

Value	Dose	Analyte	Population
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

F_unbound

Value	Dose	Co-administered	Analyte	Population
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

Dose	Population	Adverse 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

AE	Significance	Dose	Population
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

CYP3A4	CYP2C9	CYP2D6	hERG
substrate 1737 inhibitor 1587	substrate 1037 inhibitor 1767	substrate 1217 inhibitor 1852	inhibitor 1612

OverviewOther

Other Inhibitor	Other Substrate	Other 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

Target	Modality	Activity	Clinical evidence
CYP1A 121	inducer 1573 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2011/201917Orig1s000ClinPharmR.pdf#page=89 Page: 89.0	likely
UGT1A1 254	inhibitor 3277 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2011/201917Orig1s000ClinPharmR.pdf#page=50 Page: 50.0	no
P-gp 1650	inhibitor 3277 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2011/201917Orig1s000ClinPharmR.pdf#page=50 Page: 50.0	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 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2011/201917Orig1s000ClinPharmR.pdf#page=50 Page: 50.0
CYP2C19 1553	inducer 1573 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2011/201917Orig1s000ClinPharmR.pdf#page=89 Page: 89.0	unlikely
CYP3A 298	inducer 1573 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2011/201917Orig1s000ClinPharmR.pdf#page=89 Page: 89.0	unlikely
OATP1B1 803	inhibitor 3277 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2011/201917Orig1s000ClinPharmR.pdf#page=50 Page: 50.0	unlikely
CYP1A2 1692	inhibitor 3277 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2011/201917Orig1s000ClinPharmR.pdf#page=81 Page: 81.0	weak [IC50 >100 uM]
CYP2A6 739	inhibitor 3277 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2011/201917Orig1s000ClinPharmR.pdf#page=81 Page: 81.0	weak [IC50 >100 uM]
CYP2B6 1001	inhibitor 3277 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2011/201917Orig1s000ClinPharmR.pdf#page=81 Page: 81.0	weak [IC50 >100 uM]
CYP2C19 1553	inhibitor 3277 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2011/201917Orig1s000ClinPharmR.pdf#page=81 Page: 81.0	weak [IC50 >100 uM]
CYP2C8 965	inhibitor 3277 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2011/201917Orig1s000ClinPharmR.pdf#page=81 Page: 81.0	weak [IC50 >100 uM]
CYP2C9 1819	inhibitor 3277 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2011/201917Orig1s000ClinPharmR.pdf#page=81 Page: 81.0	weak [IC50 >100 uM]
CYP2D6 1891	inhibitor 3277 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2011/201917Orig1s000ClinPharmR.pdf#page=81 Page: 81.0	weak [IC50 >100 uM]
CYP2E1 970	inhibitor 3277 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2011/201917Orig1s000ClinPharmR.pdf#page=81 Page: 81.0	weak [IC50 >100 uM]
CYP3A4 1925	inhibitor 3277 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2011/201917Orig1s000ClinPharmR.pdf#page=81 Page: 81.0	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 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2011/201917Orig1s000ClinPharmR.pdf#page=81 Page: 81.0

Drug as victim

Target	Modality	Activity	Clinical evidence
CYP3A4 1737	substrate 3367 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2011/201917Orig1s000ClinPharmR.pdf#page=48 Page: 48.0	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 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2011/201917Orig1s000ClinPharmR.pdf#page=48 Page: 48.0
CYP1A2 1054	substrate 3367 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2011/201917Orig1s000ClinPharmR.pdf#page=48 Page: 48.0	no
CYP2C19 991	substrate 3367 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2011/201917Orig1s000ClinPharmR.pdf#page=48 Page: 48.0	no
CYP2C9 1037	substrate 3367 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2011/201917Orig1s000ClinPharmR.pdf#page=48 Page: 48.0	no
CYP2D6 1217	substrate 3367 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2011/201917Orig1s000ClinPharmR.pdf#page=48 Page: 48.0	no
CYP2E1 667	substrate 3367 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2011/201917Orig1s000ClinPharmR.pdf#page=48 Page: 48.0	no
P-gp 1537	substrate 3367 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2011/201917Orig1s000ClinPharmR.pdf#page=49 Page: 49.0	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 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2011/201917Orig1s000ClinPharmR.pdf#page=49 Page: 49.0

Tox targets

Target	Modality	Activity	Metabolite	Clinical evidence
hERG 1647	inhibitor 1626 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2011/201917Orig1s000PharmR.pdf#page=20 Page: 20.0

Sourcing

Vendor/Aggregator	ID	URL
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

Title	Date	PubMed
Non-HIV antivirals - a review of the recent patent literature.	2002 Aug	12802698
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	14766754
P4 and P1' optimization of bicycloproline P2 bearing tetrapeptidyl alpha-ketoamides as HCV protease inhibitors.	2004 Oct 4	15341970
Discovery of small-molecule inhibitors of HCV NS3-4A protease as potential therapeutic agents against HCV infection.	2005	16181135
In vitro studies of cross-resistance mutations against two hepatitis C virus serine protease inhibitors, VX-950 and BILN 2061.	2005 Nov 4	16087668
Potent inhibitors of the hepatitis C virus NS3 protease: use of a novel P2 cyclopentane-derived template.	2006 Aug 1	16675222
VX-950, a novel hepatitis C virus (HCV) NS3-4A protease inhibitor, exhibits potent antiviral activities in HCv replicon cells.	2006 May	16641454
Inhibitors of hepatitis C virus NS3.4A protease. Effect of P4 capping groups on inhibitory potency and pharmacokinetics.	2007 Jun 15	17482818
Preclinical characteristics of the hepatitis C virus NS3/4A protease inhibitor ITMN-191 (R7227).	2008 Dec	18824605
Hepatitis C protease and polymerase inhibitors in development.	2008 Jun	18479202
The hepatitis C virus replicon presents a higher barrier to resistance to nucleoside analogs than to nonnucleoside polymerase or protease inhibitors.	2008 May	18285474
Inhibitors of hepatitis C virus NS3/4A: alpha-ketoamide based macrocyclic inhibitors.	2009 Apr 15	19285390
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	19894743
Substituted imidazopyridines as potent inhibitors of HCV replication.	2009 May	19303654
Synthesis of potent antitumor and antiviral benzofuran derivatives.	2009 May 1	19345581
Advances in the development of macrocyclic inhibitors of hepatitis C virus NS3-4A protease.	2010	20536420
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
A cell protection screen reveals potent inhibitors of multiple stages of the hepatitis C virus life cycle.	2010 Feb 23	20142494
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
Preclinical characterization of BI 201335, a C-terminal carboxylic acid inhibitor of the hepatitis C virus NS3-NS4A protease.	2010 Nov	20823284
Selective irreversible inhibition of a protease by targeting a noncatalytic cysteine.	2011 Jan	21113170
Elimination of hepatitis C virus by short term NS3-4A and NS5B inhibitor combination therapy in human hepatocyte chimeric mice.	2011 May	21145818
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
Telaprevir: pharmacokinetics and drug interactions.	2012	22954756
Discovery of novel urea-based hepatitis C protease inhibitors with high potency against protease-inhibitor-resistant mutants.	2012 Apr 12	22471376
Telaprevir: an oral protease inhibitor for hepatitis C virus infection.	2012 Jan 1	22180548
Telaprevir for the treatment of hepatitis C.	2012 Mar	22332992
Azetidines and spiro azetidines as novel P2 units in hepatitis C virus NS3 protease inhibitors.	2013 Dec 1	24135727
Resistance studies of a dithiazol analogue, DBPR110, as a potential hepatitis C virus NS5A inhibitor in replicon systems.	2013 Feb	23165461
Myriberine A, a new alkaloid with an unprecedented heteropentacyclic skeleton from Myrioneuron faberi.	2013 Feb 1	23320525
In vitro efficacy of approved and experimental antivirals against novel genotype 3 hepatitis C virus subgenomic replicons.	2013 Nov	24013001
Synthesis and antiviral activity of a novel class of (5-oxazolyl)phenyl amines.	2013 Nov	23999140
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
Inhibition of hepatitis C virus replication by GS-6620, a potent C-nucleoside monophosphate prodrug.	2014	24419349
Preclinical characterization of the novel hepatitis C virus NS3 protease inhibitor GS-9451.	2014	23939899
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
Rhabdomyolysis in a hepatitis C virus infected patient treated with telaprevir and simvastatin.	2014 Jul-Aug	24927617
Hepatitis C virus: Virology, diagnosis and treatment.	2015 Jun 8	26052383
Systems pharmacological analysis of drugs inducing stevens-johnson syndrome and toxic epidermal necrolysis.	2015 May 18	25811541

Patents

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).

Name

Type

Language

TELAPREVIR

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