Telaprevir

Summary

Telaprevir (CHEMBL231813) is an approved small-molecule hepatitis C protease inhibitor (ATC J05AP02) targeting CTSA and CELA1; indicated across 7 conditions including chronic hepatitis c virus infection and viral infectious disease.

At a glance

• Status: Approved (max clinical phase 4)
• Modality: Small molecule
• ATC class: J05AP02
• Targets: 2 (CTSA, CELA1)
• Indications: 7 conditions
• Clinical trials: 77
• Chemistry: 679.8 Da · C36H53N7O6

Identifiers

Drug identity and classification

Field	Value
ChEMBL ID	CHEMBL231813
Name	Telaprevir
Type	Small molecule
Max phase	4
FDA approved	no
PubChem CID	3010818
ChEBI	CHEBI:68595
ATC	J05AP02
Molecular formula	C36H53N7O6
Molecular weight	679.8
InChIKey	BBAWEDCPNXPBQM-GDEBMMAJSA-N

SMILES: CCC[C@@H](C(=O)C(=O)NC1CC1)NC(=O)[C@@H]2[C@H]3CCC[C@H]3CN2C(=O)[C@H](C(C)(C)C)NC(=O)[C@H](C4CCCCC4)NC(=O)C5=NC=CN=C5

IUPAC name: (3S,3aS,6aR)-2-[(2S)-2-[[(2S)-2-cyclohexyl-2-(pyrazine-2-carbonylamino)acetyl]amino]-3,3-dimethylbutanoyl]-N-[(3S)-1-(cyclopropylamino)-1,2-dioxohexan-3-yl]-3,3a,4,5,6,6a-hexahydro-1H-cyclopenta[c]pyrrole-3-carboxamide

ChEBI definition: An oligopeptide consisting of N-(pyrazin-2-ylcarbonyl)cyclohexylalanyl, 3-methylvalyl, octahydrocyclopenta[c]pyrrole-1-carboxy, and 3-amino-N-cyclopropyl-2-oxohexanamide residues joined in sequence. Used for treatment of chronic hepatitis C virus genotype 1 infection.

Pharmacological roles (ChEBI): peptidomimetic, hepatitis C protease inhibitor, antiviral drug.

Also known as: Incivek, Incivo, LY 570310, LY-570310, MP 424, MP-424, Telaprevir, VRT 111950, VRT-111950, VX 950, VX-950, telaprevir

Parent form; salt/anhydrous children: CHEMBL573043

Patent coverage: 1,406 distinct patent families (3,301 SureChEMBL compound mentions), from 2 matched compound structure(s). One matched structure accounts for 3,079 (93%) of the total. Mentions count patents naming the compound (not distinct inventions), so promiscuous / reference molecules inflate the mention figure — families are the dedup metric.

Targets

Targets

Primary targets (GtoPdb curated mechanism): the Cancer dependency column is the DepMap CRISPR fitness signal (% of screened cell lines dependent on the target).

Gene	Target	Action	pAffinity	Cancer dependency	UniProt
CTSA	Cathepsin A	Inhibition	7	0.1%	P10619
CELA1	chymotrypsin like elastase 1	Inhibition	7.52	0.6%	Q9UNI1
	CoV 3C-like (main) protease	Inhibition	4.94

Broader ChEMBL bioactivity targets: 10 (assay-derived). Sample: Plasminogen, Neutrophil elastase, Cathepsin K, Cathepsin S, Chymotrypsin-like elastase family member 1, Cathepsin L2, Procathepsin L, Chymase, Cathepsin B, Replicase polyprotein 1ab.

Bioactivity

ChEMBL activities: 13 potent at pChembl ≥ 5 of 15 total. Top 30 by potency (10 = 0.1 nM, 6 = 1 µM):

Target	pChembl	Type	Value	Unit	Activity ID
CMA1	7.58	IC50	26	nM	CHEMBL_ACT_3450463
CELA1	7.52	IC50	30	nM	CHEMBL_ACT_3450459
CTSB	6.68	IC50	210	nM	CHEMBL_ACT_12165653
CTSS	6.52	IC50	300	nM	CHEMBL_ACT_3450451
CTSK	6.2	IC50	630	nM	CHEMBL_ACT_3450445
ELANE	6.17	IC50	680	nM	CHEMBL_ACT_5216488
CTSV	5.87	IC50	1350	nM	CHEMBL_ACT_3450442
CTSB	5.64	IC50	2300	nM	CHEMBL_ACT_5216485
CTSL	5.46	IC50	3500	nM	CHEMBL_ACT_3450440
CTSB	5.36	IC50	4400	nM	CHEMBL_ACT_3450439
ELANE	5.1	IC50	8000	nM	CHEMBL_ACT_13501525
ELANE	5.1	IC50	8000	nM	CHEMBL_ACT_3450438
PLG	5.06	IC50	8700	nM	CHEMBL_ACT_13501517

Target pathways

Aggregated over 2 target gene(s): CTSA, CELA1.

Top Reactome pathways

5 total, by targets touching each:

Pathway	Targets	Genes
MHC class II antigen presentation	1	CTSA
Sialic acid metabolism	1	CTSA
Defective NEU1 causes sialidosis	1	CTSA
Neutrophil degranulation	1	CTSA
Glycosphingolipid catabolism	1	CTSA

Dominant GO biological processes

GO term	Targets
proteolysis	2
intracellular protein transport	1
regulation of protein stability	1
regulation of chaperone-mediated autophagy	1
negative regulation of chaperone-mediated autophagy	1
negative regulation of transcription by RNA polymerase II	1
transcription by RNA polymerase II	1
inflammatory response	1
post-embryonic development	1
Wnt signaling pathway	1
exocrine pancreas development	1
multicellular organism growth	1
regulation of cell population proliferation	1
regulation of cell differentiation	1
positive regulation of angiogenesis	1

Indications & clinical

Indications

7 indications (2 at ChEMBL trial phase 4). Phase below is the highest clinical-trial phase recorded for this drug against each disease — not the molecule’s overall approval status (that is in the Summary).

Indication	Trial phase	MONDO	EFO
chronic hepatitis C virus infection	4	MONDO:0005354	EFO:0004220
viral infectious disease	4	MONDO:0005108	EFO:0000763
hepatitis C virus infection	3	MONDO:0005231	EFO:0003047
HIV infectious disease	3	MONDO:0005109	EFO:0000764
thrombocytopenia	2	MONDO:0002049	HP:0001873
liver disorder	1	MONDO:0005154	EFO:0001421

1 further indication record had no mapped disease name (EFO/MeSH-only) or were duplicates, and are omitted.

Clinical trials

Total trials: 77.

Phase distribution

Phase	Trials
PHASE3	25
PHASE2	21
PHASE1	18
Not specified	6
PHASE4	5
PHASE2/PHASE3	1
PHASE1/PHASE2	1

Top trials by phase / activity

NCT	Phase	Status	Title
NCT01415141	PHASE4	WITHDRAWN	Peginterferon and Ribavirin, With or Without Telaprevir, for Genotype 1 Hepatitis C and IL28B CC Polymorphism
NCT01467492	PHASE4	TERMINATED	Telaprevir, Peg-IFN-alfa-2a, and RBV in Treatment-Experienced Black/African American and Non-Black/African American Subjects With Genotype 1 Chronic Hepatitis C
NCT01592006	PHASE4	TERMINATED	Pegylated Interferon, Ribavirin, Telaprevir in Hepatitis C Virus Infection in Orthotopic Liver Transplant Recipients
NCT01766115	PHASE4	WITHDRAWN	Hepatitis C Virus Post-Exposure Prophylaxis for Health Care Workers
NCT02087111	PHASE4	COMPLETED	Telaprevir in Genotype 3 HCV
NCT00627926	PHASE3	COMPLETED	A Phase 3 Study of Telaprevir in Combination With Pegasys® and Copegus® in Treatment-Naive Subjects With Genotype 1 Hepatitis C Virus (HCV)
NCT00703118	PHASE3	COMPLETED	A Safety and Effectiveness Study of Telaprevir in Chronic, Genotype 1, Hepatitis C Patients That Failed Previous Standard Treatment
NCT00758043	PHASE3	COMPLETED	A Study Evaluating 24-Week and 48-Week Telaprevir-Based Regimen in Treatment Naïve Subjects With Genotype 1 Chronic Hepatitis C Who Achieve an Extended Rapid Viral Response
NCT00780416	PHASE3	COMPLETED	Efficacy and Safety of MP-424/Peginterferon Alfa-2b/Ribavirin Combination in Treatment-Naïve Patients With Chronic Hepatitis C
NCT00780910	PHASE3	COMPLETED	Efficacy and Safety of MP-424, Peginterferon Alfa-2b, and Ribavirin in Patients With Chronic Hepatitis C Who Relapsed After Previous Interferon Based Therapy
NCT00781274	PHASE3	COMPLETED	Efficacy and Safety of MP-424, Peginterferon Alfa-2b and Ribavirin in Chronic Hepatitis C Who Have Not Achieved an Undetectable HCV RNA Level With Previous Interferon Based Therapy
NCT01054573	PHASE3	COMPLETED	VX-950-TiDP24-C219: A Roll Over Trial for Patients in the Control Group of the C216 Study Who Received Telaprevir Placebo
NCT01241760	PHASE3	COMPLETED	VX-950-C211 - A Dosing Regimen Study (Twice Daily Versus Every 8 Hours) of Telaprevir in Treatment-naïve Participants With Genotype 1 Chronic Hepatitis C Virus Infection
NCT01459913	PHASE3	TERMINATED	Efficacy of a 12-Week Regimen of Telaprevir, Pegylated Interferon, and Ribavirin in Treatment-Naive and Prior Relapser Subjects With Interleukin28B (IL28B) CC Genotype
NCT01467479	PHASE3	TERMINATED	A Study to Treat Subjects With Telaprevir, Ribavirin, and Peginterferon Who Are Coinfected With HIV and Hepatitis C Virus (HCV)
NCT01492426	PHASE3	COMPLETED	Study Comparing Daclatasvir (BMS-790052) With Telaprevir Combined With Peginterferon Alfa-2a and Ribavirin in Patients With Chronic Hepatitis C Virus Infection
NCT01498068	PHASE3	COMPLETED	Open-Label, Bridging Study of Telaprevir in Treatment-Naïve and Treatment-Experienced Russian Patients With Genotype 1 Chronic Hepatitis C
NCT01500616	PHASE3	COMPLETED	Telaprevir Open-Label Study in Co-Infected Patients
NCT01513941	PHASE3	COMPLETED	An Efficacy and Safety Study of Telaprevir in Patients Infected With Both Chronic Hepatitis C Virus (HCV-1) and Human Immunodeficiency Virus (HIV-1)
NCT01571583	PHASE3	COMPLETED	An Efficacy and Safety Study of Telaprevir in Patients With Genotype 1 Hepatitis C Infection After Liver Transplantation
NCT01598090	PHASE3	COMPLETED	Phase 3 Efficacy and Safety Study of Peginterferon Lambda-1a and Ribavirin With Telaprevir
NCT01718145	PHASE3	COMPLETED	A Phase 3, Comparative Study of Asunaprevir and Daclatasvir Combination Therapy Versus Telaprevir Therapy in Japanese HCV Subjects
NCT01718158	PHASE3	COMPLETED	Efficacy and Safety Evaluation of a Regimen Consisting of Peginterferon Lambda-1a + Ribavirin + Daclatasvir (Lambda + RBV + DCV) in HCV Genotype 1b Treatment naïve Patients or Prior Relapsers to Peginterferon Alfa + Ribavirin (Alfa + RBV) Therapy
NCT01753557	PHASE3	COMPLETED	Efficacy and Safety of MP-424, Peginterferon Alfa-2a (PEG-IFN Alfa-2a), and Ribavirin(RBV) in Treatment-Naïve or Relapsed Hepatitis C
NCT01753570	PHASE3	COMPLETED	Efficacy and Safety of MP-424, Interferon Beta (IFN Beta), and Ribavirin(RBV) in Treatment-Naïve or Having Received Interferon Based Therapy With Chronic Hepatitis C (CHC)
NCT01821963	PHASE3	TERMINATED	Telaprevir Plus Standard of Care (SOC) in HCV Associated Hepatocellular Carcinoma (HCC)
NCT01854528	PHASE3	COMPLETED	A Study to Evaluate the Efficacy and Safety of Three Experimental Drugs Compared With Telaprevir (a Licensed Product) for Treatment of Chronic Hepatitis C Infection in Treatment-experienced Adults
NCT01854697	PHASE3	COMPLETED	A Study to Evaluate the Efficacy and Safety of Three Experimental Drugs Compared With Telaprevir (a Licensed Product) in People With Hepatitis C Virus Infection Who Have Not Had Treatment Before
NCT01858961	PHASE3	WITHDRAWN	Open Label Trial to Compare BI 207127 to Telaprevir in HCV Patients
NCT01890772	PHASE2/PHASE3	WITHDRAWN	Vitamin D + Telaprevir + Peginterferon + Ribavirin for of Hepatitis C Genotype 1
NCT02006745	PHASE3	COMPLETED	Open Label Trial of PEG-IFN, RBV & TVR vs. PEG-IFN & RBV Alone in Tx of HCV-1 in HIV-1 Co-infected Patients (CHAT)
NCT00262483	PHASE2	COMPLETED	Phase 2 Study of VX-950, Pegasys and Copegus in Hepatitis C
NCT00336479	PHASE2	COMPLETED	Phase 2 Study of VX-950, Pegasys®, and Copegus® in Hepatitis C
NCT00372385	PHASE2	COMPLETED	Phase 2 Study of VX-950, Pegasys® With and Without Copegus® in Hepatitis C
NCT00420784	PHASE2	COMPLETED	A Study of Telaprevir (VX-950), Pegasys and Copegus in Hepatitis C (PROVE3)
NCT00528528	PHASE2	COMPLETED	An Open-Label Study of Telaprevir Administered Every 12 or 8 Hours in Combination With One of Two Pegylated Interferons and Ribavirin in Treatment-Naive Genotype 1 Chronic Hepatitis C Participants
NCT00535847	PHASE2	COMPLETED	A Rollover Study for Subjects Participating in the Control Arm of Study VX06-950-106, VX05-950-104 and VX05-950-104EU Whose Plasma Hepatitis C Virus (HCV) Ribonucleic Acid (RNA) Levels Did Not Respond to Therapy
NCT00561015	PHASE2	COMPLETED	A Phase 2a Study to Evaluate Viral Kinetics and Safety of Telaprevir in Participants With Genotype 2 or 3 Hepatitis C Infection
NCT00580801	PHASE2	COMPLETED	An Exploratory Study of Telaprevir in Treatment-Naive Participants With Chronic Genotype 4 Hepatitis C Virus Infection
NCT00621296	PHASE2	COMPLETED	Safety and Efficacy of MP-424 to Treat Chronic Hepatitis C

Clinical evidence (CIViC)

No CIViC predictive evidence (expected for non-precision-medicine drugs).

Pharmacology

Pharmacogenomics

No CPIC/DPWG dosing guideline, but PharmGKB curates 3 clinical and 34 variant annotation(s) for this drug (gene-keyed; see PharmGKB).

Related molecules

Related molecules

Molecules sharing ≥1 of this drug’s curated primary targets, merged from two biobtree sources and ranked by shared-target count, then clinical phase: ChEMBL clinical-stage candidates (development phase ≥2) and PubChem drug-class bioactivity (approved / known drugs acting on the target). Deduplicated by drug name; the drug’s own salt forms are excluded. Note: for a drug with few primary targets a shared-target match can reflect off-target / promiscuous binding rather than the same therapeutic mechanism — the phase ordering surfaces bona-fide therapeutics first.

4 molecules share ≥1 primary target. Top 4 by shared-target count:

Molecule	Source	Status	Shared targets
BORTEZOMIB	ChEMBL + PubChem	Phase 4 (approved)	CTSA
ISOFLUROPHATE	ChEMBL	Phase 4 (approved)	CTSA
Carfilzomib	PubChem	Approved	CTSA
Sofosbuvir	PubChem	Approved	CTSA