boceprevir Indications/Contra | FAERs-F | FAERs-M | Orange Bk | BioActivity |

Stem definitionDrug idCAS RN
Hepatitis Virus C (HVC) protease inhibitors 4172 394730-60-0

Description:

MoleculeDescription

Molfile Inchi Smiles

Synonyms:

  • boceprevir
  • victrelis
  • SCH 503034
Boceprevir is an inhibitor of the HCV NS3/4A protease that is necessary for the proteolytic cleavage of the HCV encoded polyprotein into mature forms of the NS4A, NS4B, NS5A and NS5B proteins. Boceprevir covalently, yet reversibly, binds to the NS3 protease active site serine (S139) through an (alpha)-ketoamide functional group to inhibit viral replication in HCV-infected host cells. In a biochemical assay, boceprevir inhibited the activity of recombinant HCV genotype 1a and 1b NS3/4A protease enzymes, with Ki values of 14 nM for each subtype.
  • Molecular weight: 519.69
  • Formula: C27H45N5O5
  • CLOGP: 3.34
  • LIPINSKI: 1
  • HAC: 10
  • HDO: 4
  • TPSA: 150.70
  • ALOGS: -4.35
  • ROTB: 10

Drug dosage:

DoseUnitRoute
2.40 g O

ADMET properties:

PropertyValueReference
BDDCS (Biopharmaceutical Drug Disposition Classification System) 1 Hosey CM, Chan R, Benet LZ

Approvals:

DateAgencyCompanyOrphan
May 13, 2011 FDA MERCK SHARP DOHME

FDA Adverse Event Reporting System (Female)

MedDRA adverse event termLikelihood ratioLikelihood ratio thresholdPatients taking drug having adverse eventPatients taking drug not having adverse eventPatients not taking drug having adverse eventPatients not taking drug not having adverse event
Anaemia 578.39 28.10 448 9016 255331 46421267
Dysgeusia 571.01 28.10 237 9227 40254 46636344
Fatigue 190.78 28.10 394 9070 608303 46068295
White blood cell count decreased 185.75 28.10 165 9299 112066 46564532
Red blood cell count decreased 162.52 28.10 94 9370 32529 46644069
Haemoglobin decreased 128.59 28.10 144 9320 128805 46547793
Influenza like illness 124.74 28.10 99 9365 57471 46619127
Nausea 121.71 28.10 358 9106 687096 45989502
Asthenia 98.44 28.10 203 9261 310872 46365726
Weight decreased 94.67 28.10 160 9304 210689 46465909
Decreased appetite 93.60 28.10 152 9312 193684 46482914
Hepatitis C 82.12 28.10 35 9429 6283 46670315
Vomiting 72.23 28.10 228 9236 452566 46224032
Dry mouth 71.86 28.10 71 9393 54855 46621743
Transfusion 70.85 28.10 40 9424 13191 46663407
Viral load increased 57.32 28.10 18 9446 1357 46675241
Alopecia 57.15 28.10 111 9353 162303 46514295
Insomnia 55.95 28.10 111 9353 164813 46511785
Depression 54.74 28.10 112 9352 169992 46506606
Platelet count decreased 53.05 28.10 82 9382 99942 46576656
Neutropenia 52.98 28.10 100 9364 143104 46533494
Leukopenia 51.03 28.10 66 9398 68277 46608321
Chills 47.15 28.10 76 9388 95956 46580642
Headache 41.59 28.10 199 9265 478153 46198445
Dry skin 41.08 28.10 46 9418 40970 46635628
Pruritus 40.23 28.10 124 9340 242228 46434370
Death 35.37 28.10 12 9452 335536 46341062
Memory impairment 34.97 28.10 59 9405 77278 46599320
Acute kidney injury 33.99 28.10 4 9460 235851 46440747
Rash 31.39 28.10 149 9315 356363 46320235
Hepatitis C RNULL increased 30.92 28.10 7 9457 147 46676451
Drug hypersensitivity 30.88 28.10 6 9458 243819 46432779
Irritability 28.18 28.10 32 9432 28914 46647684

FDA Adverse Event Reporting System (Male)

MedDRA adverse event termLikelihood ratioLikelihood ratio thresholdPatients taking drug having adverse eventPatients taking drug not having adverse eventPatients not taking drug having adverse eventPatients not taking drug not having adverse event
Dysgeusia 750.43 27.81 296 10587 24505 29917090
Anaemia 613.64 27.81 543 10340 207449 29734146
Fatigue 438.50 27.81 556 10327 320117 29621478
Influenza like illness 230.79 27.81 133 10750 25472 29916123
White blood cell count decreased 207.94 27.81 200 10683 83747 29857848
Rash 185.31 27.81 283 10600 191606 29749989
Red blood cell count decreased 149.39 27.81 102 10781 26219 29915376
Irritability 137.18 27.81 92 10791 22958 29918637
Nausea 128.05 27.81 311 10572 296646 29644949
Depression 108.21 27.81 148 10735 90289 29851306
Pruritus 102.08 27.81 166 10717 118038 29823557
Headache 96.02 27.81 207 10676 182099 29759496
Weight decreased 82.41 27.81 174 10709 150747 29790848
Dry skin 80.29 27.81 66 10817 22388 29919207
Decreased appetite 78.58 27.81 170 10713 149740 29791855
Hepatitis C 74.44 27.81 51 10832 13154 29928441
Leukopenia 71.78 27.81 95 10788 56064 29885531
Off label use 71.43 27.81 5 10878 249285 29692310
Dry mouth 63.16 27.81 58 10825 22792 29918803
Viral load increased 62.08 27.81 27 10856 2827 29938768
Acute kidney injury 60.39 27.81 13 10870 273829 29667766
Death 57.82 27.81 29 10854 357254 29584341
Insomnia 56.00 27.81 112 10771 93224 29848371
Haemoglobin decreased 55.85 27.81 126 10757 113972 29827623
Asthenia 53.49 27.81 189 10694 221101 29720494
Platelet count decreased 52.83 27.81 118 10765 106011 29835584
Alopecia 51.47 27.81 48 10835 19227 29922368
Neutropenia 51.14 27.81 131 10752 128409 29813186
Product quality issue 48.69 27.81 46 10837 18728 29922867
Chills 47.25 27.81 90 10793 72248 29869347
Memory impairment 46.10 27.81 62 10821 37112 29904483
Transfusion 42.47 27.81 29 10854 7432 29934163
Injection site rash 41.78 27.81 22 10861 3517 29938078
Vomiting 37.91 27.81 169 10714 219649 29721946
Hepatic cirrhosis 37.34 27.81 37 10846 15962 29925633
Mood swings 37.27 27.81 27 10856 7599 29933996
Ascites 37.25 27.81 55 10828 35866 29905729
Pollakiuria 33.84 27.81 36 10847 16870 29924725
Rash pruritic 33.23 27.81 41 10842 22531 29919064
Thrombocytopenia 30.41 27.81 114 10769 136930 29804665

Pharmacologic Action:

SourceCodeDescription
ATC J05AP03 ANTIINFECTIVES FOR SYSTEMIC USE
ANTIVIRALS FOR SYSTEMIC USE
DIRECT ACTING ANTIVIRALS
Antivirals for treatment of HCV infections
FDA MoA N0000182141 Cytochrome P450 3A4 Inhibitors
FDA MoA N0000182638 HCV NS3/4A Protease Inhibitors
FDA EPC N0000182639 Hepatitis C Virus NS3/4A Protease Inhibitor
FDA MoA N0000190115 Cytochrome P450 3A5 Inhibitors
CHEBI has role CHEBI:36044 anti-virus drug
CHEBI has role CHEBI:63175 peptidomimetics
CHEBI has role CHEBI:64924 hepatitis c protease inhibitors

Drug Use (View source of the data)

DiseaseRelationSNOMED_IDDOID
Chronic hepatitis C indication 128302006
Anemia contraindication 271737000 DOID:2355
Neutropenic disorder contraindication 303011007 DOID:1227

Acid dissociation constants calculated using MoKa v3.0.0

Dissociation levelDissociation constantType (acidic/basic)
pKa1 12.84 acidic
pKa2 13.48 acidic
pKa3 13.89 acidic

Orange Book patent data (new drug applications)

None

Orange Book exclusivity data (new drug applications)

None

Bioactivity Summary:

TargetClassPharosUniProtActionTypeActivity value
(-log[M])
Mechanism
action
Bioact sourceMoA source
Lysosomal protective protein Enzyme INHIBITOR IC50 6 IUPHAR
Cathepsin F Enzyme IC50 5.96 CHEMBL
Cathepsin K Enzyme IC50 7.40 CHEMBL
Cathepsin B Enzyme IC50 5.21 CHEMBL
Cathepsin L2 Enzyme IC50 7.12 CHEMBL
Neutrophil elastase Enzyme IC50 4.77 CHEMBL
Chymase Enzyme IC50 7.49 CHEMBL
Cathepsin S Enzyme IC50 6.92 CHEMBL
Cathepsin L1 Enzyme IC50 6.12 CHEMBL
Hepatitis C virus serine protease, NS3/NS4A Enzyme INHIBITOR Ki 8.96 CHEMBL CHEMBL
Nonstructural protein NS3-4A Unclassified Ki 7.85 CHEMBL

External reference:

IDSource
89BT58KELH UNII
4030728 VUID
N0000182738 NUI
D08876 KEGG_DRUG
4030728 VANDF
C1738934 UMLSCUI
CHEBI:68621 CHEBI
CHEMBL218394 ChEMBL_ID
DB08873 DRUGBANK_ID
8840 INN_ID
10324367 PUBCHEM_CID
7876 IUPHAR_LIGAND_ID
C512204 MESH_SUPPLEMENTAL_RECORD_UI
1102129 RXNORM
181444 MMSL
27875 MMSL
d07774 MMSL
013772 NDDF
698183007 SNOMEDCT_US
703961009 SNOMEDCT_US

Pharmaceutical products:

None