Boceprevir

Summary

Boceprevir (CHEMBL218394) is an approved small-molecule hepatitis C protease inhibitor (ATC J05AP03) targeting CTSA; indicated across 4 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: J05AP03
• Targets: 1 (CTSA)
• Indications: 4 conditions
• Clinical trials: 51
• Chemistry: 519.7 Da · C27H45N5O5

Identifiers

Drug identity and classification

Field	Value
ChEMBL ID	CHEMBL218394
Name	Boceprevir
Type	Small molecule
Max phase	4
FDA approved	no
PubChem CID	10324367
ChEBI	CHEBI:68621
ATC	J05AP03
Molecular formula	C27H45N5O5
Molecular weight	519.7
InChIKey	LHHCSNFAOIFYRV-DOVBMPENSA-N

SMILES: CC1([C@@H]2[C@H]1[C@H](N(C2)C(=O)[C@H](C(C)(C)C)NC(=O)NC(C)(C)C)C(=O)NC(CC3CCC3)C(=O)C(=O)N)C

IUPAC name: (1R,2S,5S)-N-(4-amino-1-cyclobutyl-3,4-dioxobutan-2-yl)-3-[(2S)-2-(tert-butylcarbamoylamino)-3,3-dimethylbutanoyl]-6,6-dimethyl-3-azabicyclo[3.1.0]hexane-2-carboxamide

ChEBI definition: A synthetic tripeptide consisting of N-(tert-butylcarbamoyl)-3-methyl-L-valyl, a cyclopropyl-fused prolyl and 3-amino-4-cyclobutyl-2-oxobutanamide residues joined in sequence. Used for treatment of chronic hepatitis C virus genotype 1 infection.

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

Also known as: Boceprevir, EBP 520, EBP-520, SCH 503034, Sch 50304, SCH-503034, Victrelis, boceprevir, BOCEPREVIR, [14C]boceprevir, C0088691

Patent coverage: 1,228 distinct patent families (2,760 SureChEMBL compound mentions), from 1 matched compound structure(s). 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	6	0.1%	P10619
	CoV 3C-like (main) protease	Inhibition	6.02

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

Bioactivity

ChEMBL activities: 20 potent at pChembl ≥ 5 of 23 total. Top 30 by potency (10 = 0.1 nM, 6 = 1 µM):

Target	pChembl	Type	Value	Unit	Activity ID
CMA1	7.5	IC50	32	nM	CHEMBL_ACT_3450538
CTSK	7.4	IC50	40	nM	CHEMBL_ACT_3450539
CTSV	7.12	IC50	75	nM	CHEMBL_ACT_3450540
CTSS	6.92	IC50	120	nM	CHEMBL_ACT_3450541
CTSL	6.12	IC50	760	nM	CHEMBL_ACT_3450542
CTSF	5.96	IC50	1100	nM	CHEMBL_ACT_3450543
P0DTD1	5.93	Ki	1180	nM	CHEMBL_ACT_24977648
P0DTD1	5.8	IC50	1590	nM	CHEMBL_ACT_24977692
P0DTD1	5.4	IC50	4000	nM	CHEMBL_ACT_25516033
P0DTD1	5.39	IC50	4100	nM	CHEMBL_ACT_25930826
P0DTD1	5.38	IC50	4130	nM	CHEMBL_ACT_24660834
P0DTD1	5.38	IC50	4130	nM	CHEMBL_ACT_24660862
P0DTD1	5.38	IC50	4130	nM	CHEMBL_ACT_24660880
P0DTD1	5.38	IC50	4200	nM	CHEMBL_ACT_24742886
P0DTD1	5.38	IC50	4130	nM	CHEMBL_ACT_24822809
CTSB	5.21	IC50	6200	nM	CHEMBL_ACT_5216484
P0C6U8	5.18	IC50	6630	nM	CHEMBL_ACT_25952117
P0DTD1	5.1	IC50	8000	nM	CHEMBL_ACT_24742887
P0DTD1	5.1	IC50	8000	nM	CHEMBL_ACT_25952143
P0DTD1	5.08	Kd	8370	nM	CHEMBL_ACT_25874177

Target pathways

Aggregated over 1 target gene(s): CTSA.

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	1
intracellular protein transport	1
regulation of protein stability	1
regulation of chaperone-mediated autophagy	1
negative regulation of chaperone-mediated autophagy	1

Indications & clinical

Indications

4 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
thrombocytopenia	1	MONDO:0002049	HP:0001873

Clinical trials

Total trials: 51.

Phase distribution

Phase	Trials
PHASE3	19
PHASE1	10
Not specified	8
PHASE4	6
PHASE2	6
PHASE2/PHASE3	1
EARLY_PHASE1	1

Top trials by phase / activity

NCT	Phase	Status	Title
NCT01443923	PHASE4	TERMINATED	Boceprevir Drug Combination for Hepatitis C Treatment in People With and Without HIV
NCT01591460	PHASE4	COMPLETED	A Triple Combination Therapy Study of Boceprevir, Pegasys and Copegus in Previously Untreated Patients With Genotype 1 Chronic Hepatitis C
NCT01731301	PHASE4	UNKNOWN	A Pilot Study to Treat Patients With Chronic Hepatitis C Virus (HCV) Genotype 1 and End-Stage Renal Disease (ESRD)
NCT01756079	PHASE4	COMPLETED	A Study to Evaluate the Efficacy and Safety of Boceprevir Added to Standard of Care Therapy in Previously Treated Participants With Chronic Hepatitis C Genotype 1 and Cirrhosis (MK-3034-105)
NCT01770223	PHASE4	WITHDRAWN	A Study of Viral Response to Triple Therapy in Hepatitis C Virus-Infected Participants With Insulin Resistance Who Failed Dual Therapy (MK-3034-113)
NCT01925183	PHASE4	COMPLETED	Individualized Triple-therapy Using Boceprevir in HIV-positive Patients With Hepatitis C
NCT00689390	PHASE2/PHASE3	TERMINATED	Three-year Follow-up of Participants After Administration of Boceprevir or Narlaprevir for the Treatment of Chronic Hepatitis C (P05063)
NCT00705432	PHASE3	COMPLETED	Safety and Efficacy of Boceprevir in Previously Untreated Subjects With Chronic Hepatitis C Genotype 1 (Study P05216AM2) (COMPLETED)
NCT00708500	PHASE3	COMPLETED	Boceprevir in Subjects With Chronic Hepatitis C Genotype 1 Who Failed Prior Treatment With Peginterferon/Ribavirin (Study P05101AM3)(COMPLETED)
NCT00845065	PHASE3	COMPLETED	Boceprevir in Combination With Peginterferon Alfa-2a and Ribavirin in Participants With Chronic Hepatitis C Genotype 1 Who Failed Prior Treatment With Peginterferon/Ribavirin (Study P05685AM2)(COMPLETED)
NCT00910624	PHASE3	COMPLETED	Boceprevir Treatment in Participants With Chronic Hepatitis C Genotype 1 Deemed Nonresponders to Peginterferon/Ribavirin (P05514)
NCT01023035	PHASE3	COMPLETED	Boceprevir/Peginterferon/Ribavirin for Chronic Hepatitis C: Erythropoietin Use Versus Ribavirin Dose Reduction for Anemia (P06086 AM2)
NCT01390844	PHASE3	COMPLETED	Safety and Efficacy of Boceprevir in Asia Pacific Participants With Chronic Hepatitis C Genotype 1 (P07063)
NCT01425203	PHASE3	COMPLETED	The Effect of Boceprevir in Russian Participants Diagnosed With Chronic Hepatitis C Genotype 1 (P08160)
NCT01446250	PHASE3	TERMINATED	Alisporivir (Deb025) and Boceprevir Triple Therapies in African American Participants Not Previously Treated for Chronic Hepatitis C Genotype 1
NCT01457937	PHASE3	UNKNOWN	Boceprevir/PegIFN α-2b/Riba in HCV+ Gt1 Menopausal Women, Nonresponders to PegIFN/Riba or Treatment-naives (MEN_BOC)
NCT01482767	PHASE3	COMPLETED	Evaluating the Effectiveness of Boceprevir, Pegylated-Interferon Alfa 2b and Ribavirin in Treating Hepatitis C Virus (HCV) Infection in Adults With HIV and HCV Infection
NCT01544920	PHASE3	COMPLETED	Safety and Efficacy of Boceprevir/Peginterferon Alfa-2a/Ribavirin in Interleukin-28B CC Allele-Positive Chronic Hepatitis C Virus (HCV) Genotype 1 Participants (P07755)
NCT01585584	PHASE3	COMPLETED	Triple-Therapy in Patients With HCV Genotype 3 Who Previously Failed Treatment
NCT01590225	PHASE3	WITHDRAWN	Efficacy and Safety of Boceprevir in Combination With Peginterferon Alfa-2b Plus Ribavirin in Pediatric Subjects With Chronic Hepatitis C Genotype 1 (P08034)
NCT01641666	PHASE3	WITHDRAWN	Safety and Tolerability of Boceprevir in Combination With Peginterferon Alfa-2b Plus Ribavirin for the Treatment of Vietnamese Subjects With Chronic Hepatitis C Genotype 1 (P08599)
NCT01653236	PHASE3	UNKNOWN	Boceprevir With Peginterferon Alfa-2b and Ribavirin in the Treatment-naive Patients Infected With Genotype 4 Chronic Hepatitis C Infection
NCT01718301	PHASE3	TERMINATED	HIV Patients With Chronic Hepatitis C Genotype 1 Infection Who Failed Previously to Peginterferon /Ribavirin
NCT01945294	PHASE3	COMPLETED	Short Duration Versus Standard Response-Guided Therapy With Boceprevir Combined With PegIntron and Ribavirin in Previously Untreated Non-Cirrhotic Asian Participants With Chronic HCV Genotype 1 (MK-3034-107)
NCT02160080	PHASE3	UNKNOWN	Boceprevir Treatment in Liver Pre-transplant HCV Patients
NCT02204475	PHASE3	WITHDRAWN	Grazoprevir (MK-5172)/Elbasvir (MK-8742) Versus Boceprevir/Pegylated Interferon/Ribavarin for Chronic Hepatitis C Infection (MK-5172-066)
NCT00160251	PHASE2	COMPLETED	Boceprevir (SCH 503034) Plus Peg-Intron, With and Without Added Ribavirin, in Patients With Chronic Hepatitis C, Genotype 1, Who Did Not Respond to Previous Treatment With Peginterferon Alfa Plus Ribavirin (Study P03659AM2)(COMPLETED)
NCT00959699	PHASE2	COMPLETED	A Phase 2b, Safety and Efficacy Study of Boceprevir in Patients Coinfected With HIV and Hepatitis C (P05411 AM4)
NCT01353911	PHASE2	COMPLETED	Grazoprevir (MK-5172) Administered With Peginterferon and Ribavirin in Treatment-Naïve Participants With Chronic Hepatitis C (MK-5172-003)
NCT01463956	PHASE2	COMPLETED	Efficacy of PegInterferon-Ribavirin-Boceprevir Therapy in Patients Infected With G1 HCV With Cirrhosis, Awaiting Liver Transplantation
NCT01482403	PHASE2	COMPLETED	A Study of Mericitabine in Combination With Boceprevir and Pegasys/Copegus in Patients With Chronic Hepatitis C
NCT01912495	PHASE2	COMPLETED	Dutch Acute HCV in HIV Study (DAHHS)
NCT01181804	PHASE1	COMPLETED	Comparison of Safety and Resulting Blood Level Profiles After Administration of a New Boceprevir Tablet Versus Its Current Capsule Formulation for Treatment of Chronic Hepatitis C (P06992)(COMPLETED)
NCT01288417	PHASE1	COMPLETED	Pharmacokinetic Study of the HCV Protease Inhibitor Boceprevir and the HIV Integrase Inhibitor Raltegravir
NCT01396005	PHASE1	COMPLETED	A Study to Evaluate the Pharmacokinetic Effect of SCH 503034 (Boceprevir) on Methadone or Buprenorphine/Naloxone Plasma Concentrations (P08123)
NCT01425190	PHASE1	TERMINATED	Pharmacokinetics of Boceprevir in Pediatric Subjects With Chronic Hepatitis C Genotype 1 (P07614)
NCT01470690	PHASE1	COMPLETED	Pharmacokinetic Study of the HCV Protease Inhibitor Bo-cePRevir and the Proton Pump Inhibitor OMeprazOle (PROMO)
NCT01499498	PHASE1	COMPLETED	The Boceprevir and Sildenafil Pharmacokinetics Study
NCT01597895	PHASE1	COMPLETED	Estimate the Effect of Telaprevir and Boceprevir on Maraviroc Pharmacokinetics in Healthy Subjects
NCT01627717	PHASE1	COMPLETED	The Effects of the Direct Acting Antiviral Agent Boceprevir on the Pharmacokinetics of Maraviroc in Healthy Volunteers

Clinical evidence (CIViC)

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

Pharmacology

Pharmacogenomics

No CPIC/DPWG dosing guideline, but PharmGKB curates 1 clinical and 14 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