telaprevir 🐶 Veterinary Use | Indications/Contra | FAERs-F | FAERs-M | Orange Bk | PK/Tox | Related Drugs | BioActivity |

Stem definitionDrug idCAS RN
Hepatitis Virus C (HVC) protease inhibitors 4173 402957-28-2

Description:

MoleculeDescription

Molfile Inchi Smiles

Synonyms:

  • telaprevir
  • VX 950
  • incivek
  • incivo
Telaprevir is an inhibitor of the HCV NS3/4A serine protease, 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. In a biochemical assay, telaprevir inhibited the proteolytic activity of the recombinant HCV NS3 protease domain with an IC50 value of 10 nM.
  • Molecular weight: 679.86
  • Formula: C36H53N7O6
  • CLOGP: 5.39
  • LIPINSKI: 3
  • HAC: 13
  • HDO: 4
  • TPSA: 179.56
  • ALOGS: -4.28
  • ROTB: 14
  • Status: OFM
    • Legend:
    OFP - off patent
    OFM - off market
    ONP - on patent

Drug dosage:

DoseUnitRoute
2.25 g O

ADMET properties:

PropertyValueReference
BDDCS (Biopharmaceutical Drug Disposition Classification System) 2 Hosey CM, Chan R, Benet LZ
S (Water solubility) 0.00 mg/mL Bocci G, Oprea TI, Benet LZ

Predicted pharmacokinetic/toxicological properties (PK-AZ):

PropertyDescriptionValueUnitConfidenceSimilarity
azlogd74 LogD at pH 7.4 3.902 High 1
caco2-efflux Caco-2 efflux ratio (BA/AB) 32.137 High 1
caco2-intrinsic-papp Caco-2 intrinsic apparent permeability 14.655 10^-6 cm/s High 1
dh-clint Dog hepatocyte intrinsic clearance 22.336 uL/min/10^6 cells High 1
dppb Dog plasma protein binding (% unbound) 4.480 % High 1
fcs-ppb Fetal calf serum protein binding (% unbound) 9.030 % High 1
herg hERG pIC50 4.565 pIC50 High 1
hh-clint Human hepatocyte intrinsic clearance 12.331 uL/min/10^6 cells High 1
hlm-clint Human liver microsomal intrinsic clearance 225.944 uL/min/mg protein High 1
hppb Human plasma protein binding (% unbound) 7.190 % High 1
kinase-safety-class EIF2AK3,GRK2,PDK1,PDK2 4
mdck-mdr1-efflux MDCK-MDR1 efflux ratio 10.162 High 1
mh-clint Mouse hepatocyte intrinsic clearance 36.141 High 1
mppb Mouse plasma protein binding (% unbound) 2.270 High 1
nih-mdck-mdr1-efflux NIH MDCK-MDR1 efflux ratio 41.115 High 1
pfas-class PFAS structural alert (1 = True, 0 = False) 0
pppb Pig plasma protein binding (% unbound) 6.730 % High 1
rh-clint Rat hepatocyte intrinsic clearance 37.497 uL/min/10^6 cells High 1
rh-fuinc Rat hepatocyte fraction unbound in incubation 33.590 % High 1
rppb Rat plasma protein binding (% unbound) 3.740 % High 1
solubility-dd Solubility at pH 7.4 in DMSO 24.322 uM High 1

Approvals:

DateAgencyCompanyOrphan
Sept. 19, 2011 EMA Janssen-Cilag International N.V.
May 23, 2011 FDA VERTEX PHARMS

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 430.61 38.27 205 2379 352597 90273266
Pancytopenia 142.40 38.27 69 2515 120194 90505669
Anal pruritus 125.13 38.27 22 2562 945 90624918
Rash 114.77 38.27 126 2458 795974 89829889
Thrombocytopenia 114.31 38.27 72 2512 208653 90417210
Aplastic anaemia 101.75 38.27 30 2554 13239 90612624
Leukopenia 73.85 38.27 42 2542 100668 90525195
Neutropenia 61.55 38.27 51 2533 224853 90401010
Hepatitis C 53.19 38.27 15 2569 5645 90620218
Haemoglobin decreased 51.22 38.27 40 2544 161916 90463947
Extradural abscess 40.46 38.27 9 2575 1295 90624568
Drug reaction with eosinophilia and systemic symptoms 40.07 38.27 21 2563 42737 90583126

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
Anaemia 323.39 37.08 237 3630 280041 42337427
Rash 241.92 37.08 199 3668 276755 42340713
Pruritus 144.13 37.08 126 3741 188645 42428823
Influenza like illness 78.94 37.08 44 3823 31796 42585672
Depressed mood 76.84 37.08 39 3828 23345 42594123
Thrombocytopenia 74.90 37.08 89 3778 190190 42427278
Dry skin 64.37 37.08 45 3822 48293 42569175
Fatigue 57.08 37.08 123 3744 435518 42181950
Anorectal discomfort 49.66 37.08 15 3852 2240 42615228
Skin irritation 48.15 37.08 20 3847 7554 42609914
Wrong dose 45.77 37.08 12 3855 1072 42616396
Leukopenia 43.37 37.08 43 3824 74703 42542765
Haemoglobin decreased 40.91 37.08 55 3812 132416 42485052
Anal pruritus 40.19 37.08 9 3858 413 42617055
Retinal exudates 38.89 37.08 10 3857 827 42616641
Porphyria non-acute 38.78 37.08 9 3858 485 42616983
Oral herpes 38.33 37.08 17 3850 7527 42609941
Nausea 37.67 37.08 99 3768 396700 42220768

FDA Adverse Event Reporting System (Geriatric)

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 667.61 34.42 389 5375 546697 110036838
Rash 252.43 34.42 258 5506 820706 109762829
Thrombocytopenia 192.65 34.42 153 5611 348732 110234803
Pancytopenia 160.49 34.42 112 5652 209501 110374034
Anal pruritus 158.85 34.42 30 5734 1037 110582498
Leukopenia 110.24 34.42 78 5686 148713 110434822
Pruritus 97.93 34.42 135 5629 581425 110002110
Haemoglobin decreased 82.63 34.42 82 5682 248645 110334890
Aplastic anaemia 82.52 34.42 35 5729 24273 110559262
Dry skin 76.37 34.42 55 5709 107598 110475937
Depressed mood 75.06 34.42 44 5720 60765 110522770
Neutropenia 67.49 34.42 90 5674 374530 110209005
Hepatitis C 66.75 34.42 25 5739 12548 110570987
Anorectal discomfort 66.39 34.42 19 5745 4107 110579428
Influenza like illness 62.30 34.42 45 5719 88367 110495168
Fatigue 54.27 34.42 162 5602 1215796 109367739
Drug reaction with eosinophilia and systemic symptoms 51.57 34.42 39 5725 82056 110501479
Hepatic failure 48.44 34.42 35 5729 68704 110514831
Dermatitis 47.67 34.42 25 5739 27812 110555723
Skin irritation 44.03 34.42 20 5744 16299 110567236
Retinopathy 43.72 34.42 14 5750 4415 110579120
Toxic skin eruption 42.30 34.42 23 5741 27492 110556043
Wrong dose 41.73 34.42 12 5752 2637 110580898
Nausea 36.83 34.42 144 5620 1235546 109347989

FDA Adverse Event Reporting System (Pediatric)

None

Pharmacologic Action:

SourceCodeDescription
ATC J05AP02 ANTIINFECTIVES FOR SYSTEMIC USE
ANTIVIRALS FOR SYSTEMIC USE
DIRECT ACTING ANTIVIRALS
Antivirals for treatment of HCV infections
FDA MoA N0000182638 HCV NS3/4A Protease Inhibitors
FDA EPC N0000182639 Hepatitis C Virus NS3/4A Protease Inhibitor
FDA MoA N0000185503 P-Glycoprotein Inhibitors
FDA MoA N0000190107 Organic Anion Transporting Polypeptide 1B1 Inhibitors
FDA MoA N0000190109 Organic Anion Transporting Polypeptide 2B1 Inhibitors
FDA MoA N0000190114 Cytochrome P450 3A Inhibitors
CHEBI has role CHEBI:22587 antiviral agent
CHEBI has role CHEBI:35441 antiinfective agent
CHEBI has role CHEBI:36044 antiviral drug
CHEBI has role CHEBI:63175 peptidomimetic
CHEBI has role CHEBI:64924 hepatitis C protease inhibitor
CHEBI has role CHEBI:64946 anti-HIV agent

Related Drugs by ATC class:

J05AP Antivirals for treatment of HCV infections 18 drugs
asunaprevirbeclabuvirboceprevirdaclatasvirdasabuvirelbasvirglecaprevirgrazoprevirledipasvirombitasvirparitaprevirpibrentasvir show all 18 →

Drug Use | Suggest Off label Use Form| |View source of the data|

DiseaseRelationSNOMED_IDDOID
Chronic hepatitis C indication 128302006
Anemia contraindication 271737000 DOID:2355




🐶 Veterinary Drug Use

None

🐶 Veterinary products

None

Acid dissociation constants calculated using MoKa v3.0.0

Dissociation levelDissociation constantType (acidic/basic)
pKa1 12.64 acidic
pKa2 13.65 acidic
pKa3 2.9 Basic

Orange Book patent data (new drug applications)

Formulation strengthTrade nameApplicantApplication numberApproval dateTypeDose formRoutePatent numberPatent expiration datePatent use
375MG INCIVEK VERTEX PHARMS N201917 May 23, 2011 DISCN TABLET ORAL 8431615 May 30, 2028 METHOD OF TREATING CHRONIC HEPATITIS C

Orange Book exclusivity data (new drug applications)

None

Bioactivity Summary:

TargetClassPharosUniProtActionTypeActivity value
(-log[M])		Mechanism
action		Bioact sourceMoA source
Neutrophil elastase Enzyme IC50 6.17 CHEMBL
Chymotrypsin-like elastase family member 1 Enzyme IC50 7.52 CHEMBL
Cathepsin B Enzyme IC50 6.68 CHEMBL
Cathepsin L1 Enzyme IC50 5.46 CHEMBL
Chymase Enzyme IC50 7.59 CHEMBL
Lysosomal protective protein Enzyme INHIBITOR IC50 7 IUPHAR
Cathepsin L2 Enzyme IC50 5.87 CHEMBL
Cathepsin K Enzyme IC50 6.20 CHEMBL
Cathepsin S Enzyme IC50 6.52 CHEMBL
Plasminogen Enzyme IC50 5.06 CHEMBL
Hepatitis C virus serine protease, NS3/NS4A Enzyme INHIBITOR CHEMBL CHEMBL
Replicase polyprotein 1ab Enzyme IC50 4.94 CHEMBL
NS3 protease Enzyme IC50 6.89 CHEMBL
NS3 protease Enzyme Ki 7.09 CHEMBL
NS3 protease Enzyme Ki 8.41 CHEMBL

External reference:

IDSource
4030729 VUID
N0000182739 NUI
D09012 KEGG_DRUG
4030729 VANDF
C1876229 UMLSCUI
A1DIB PDB_CHEM_ID
CHEMBL231813 ChEMBL_ID
DB05521 DRUGBANK_ID
C486464 MESH_SUPPLEMENTAL_RECORD_UI
7871 IUPHAR_LIGAND_ID
8686 INN_ID
655M5O3W0U UNII
3010818 PUBCHEM_CID
1102261 RXNORM
181488 MMSL
27888 MMSL
d07777 MMSL
013797 NDDF
698806003 SNOMEDCT_US
704466001 SNOMEDCT_US
CHEBI:68595 CHEBI

Pharmaceutical products:

None