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

Stem definitionDrug idCAS RN
antivirals, hepatitis C Virus (HCV) NS5A inhibitors 4875 1009119-64-5

Description:

MoleculeDescription

Molfile Inchi Smiles

Synonyms:

  • daclatasvir
  • daclatasvir dihydrochloride
  • daclatasvir hydrochloride
  • daklinza
  • BMS-790052-05
  • BMS-790052
  • daclatasvir HCl
  • daclatasivr
an HCV NS5A inhibitor
  • Molecular weight: 738.89
  • Formula: C40H50N8O6
  • CLOGP: 4.72
  • LIPINSKI: 2
  • HAC: 14
  • HDO: 4
  • TPSA: 174.64
  • ALOGS: -4.94
  • ROTB: 13

Drug dosage:

DoseUnitRoute
60 mg O

ADMET properties:

PropertyValueReference
BDDCS (Biopharmaceutical Drug Disposition Classification System) 4 Hosey CM, Chan R, Benet LZ
Vd (Volume of distribution) 0.67 L/kg Lombardo F, Berellini G, Obach RS
CL (Clearance) 1 mL/min/kg Lombardo F, Berellini G, Obach RS
fu (Fraction unbound in plasma) 0.01 % Lombardo F, Berellini G, Obach RS
t_half (Half-life) 13.50 hours Lombardo F, Berellini G, Obach RS

Approvals:

DateAgencyCompanyOrphan
June 27, 2014 EMA
July 24, 2015 FDA BRISTOL MYERS SQUIBB

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
Hepatocellular carcinoma 276.68 29.27 59 3262 2780 46679961
Hepatitis C 234.63 29.27 60 3261 6258 46676483
Genotype drug resistance test positive 123.78 29.27 23 3298 527 46682214
Ascites 118.89 29.27 56 3265 36528 46646213
Hepatic encephalopathy 101.71 29.27 35 3286 10122 46672619
Fatigue 80.16 29.27 149 3172 608548 46074193
Hepatic cirrhosis 73.22 29.27 31 3290 15701 46667040
Hepatic failure 72.69 29.27 39 3282 33377 46649364
Headache 63.84 29.27 118 3203 478234 46204507
Oesophageal varices haemorrhage 57.25 29.27 14 3307 1209 46681532
Liver transplant 52.24 29.27 15 3306 2402 46680339
Liver injury 50.38 29.27 24 3297 15977 46666764
Treatment failure 50.02 29.27 46 3275 93041 46589700
Hepatitis B reactivation 49.45 29.27 13 3308 1501 46681240
Virologic failure 45.51 29.27 13 3308 2042 46680699
Viral mutation identified 42.00 29.27 12 3309 1887 46680854
Renal impairment 40.41 29.27 37 3284 74335 46608406
Jaundice 34.70 29.27 23 3298 28822 46653919
Hyperbilirubinaemia 30.86 29.27 15 3306 10423 46672318

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
Hepatocellular carcinoma 860.73 23.91 227 5806 9383 29937062
Hepatitis C 847.97 23.91 240 5793 12965 29933480
Genotype drug resistance test positive 610.60 23.91 123 5910 1466 29944979
Treatment failure 487.80 23.91 202 5831 34477 29911968
Liver transplant 197.68 23.91 55 5978 2747 29943698
Viral mutation identified 146.80 23.91 43 5990 2583 29943862
Hepatic encephalopathy 128.83 23.91 61 5972 14131 29932314
Drug ineffective 127.92 23.91 237 5796 340150 29606295
Ascites 108.01 23.91 75 5958 35846 29910599
Fatigue 103.98 23.91 210 5823 320463 29625982
Headache 94.65 23.91 147 5886 182159 29764286
Hepatic cirrhosis 93.26 23.91 51 5982 15948 29930497
Hepatic cancer 74.65 23.91 33 6000 6515 29939930
Hyperbilirubinaemia 74.62 23.91 45 5988 16897 29929548
Virologic failure 74.39 23.91 27 6006 3192 29943253
Therapeutic embolisation 71.26 23.91 16 6017 326 29946119
Hepatic failure 70.78 23.91 57 5976 33986 29912459
Hepatitis B reactivation 65.99 23.91 24 6009 2853 29943592
Insomnia 54.97 23.91 80 5953 93256 29853189
Genital herpes simplex 48.89 23.91 10 6023 128 29946317
Biliary colic 45.54 23.91 14 6019 990 29945455
Varices oesophageal 44.27 23.91 19 6014 3490 29942955
Oesophageal varices haemorrhage 40.08 23.91 17 6016 3034 29943411
Genital herpes 39.78 23.91 11 6022 535 29945910
Abdominal cavity drainage 39.46 23.91 10 6023 346 29946099
Hepatorenal syndrome 36.37 23.91 15 6018 2496 29943949
Hepatitis C RNULL increased 34.04 23.91 9 6024 369 29946076
Hepatitis C RNULL positive 33.20 23.91 8 6025 224 29946221
Jaundice 32.00 23.91 36 5997 32450 29913995
Chronic hepatitis C 31.54 23.91 9 6024 491 29945954
Embolism 29.25 23.91 18 6015 6991 29939454
Hydrocholecystis 28.58 23.91 7 6026 210 29946235
Packed red blood cell transfusion 28.44 23.91 11 6022 1549 29944896
Hepatic neoplasm 26.57 23.91 11 6022 1848 29944597
Transcatheter arterial chemoembolisation 26.38 23.91 4 6029 6 29946439
Hypotension 25.06 23.91 5 6028 200560 29745885
Liver disorder 24.39 23.91 30 6003 29692 29916753

Pharmacologic Action:

SourceCodeDescription
ATC J05AP07 ANTIINFECTIVES FOR SYSTEMIC USE
ANTIVIRALS FOR SYSTEMIC USE
DIRECT ACTING ANTIVIRALS
Antivirals for treatment of HCV infections
ATC J05AP58 ANTIINFECTIVES FOR SYSTEMIC USE
ANTIVIRALS FOR SYSTEMIC USE
DIRECT ACTING ANTIVIRALS
Antivirals for treatment of HCV infections
FDA MoA N0000185503 P-Glycoprotein Inhibitors
FDA MoA N0000190107 Organic Anion Transporting Polypeptide 1B1 Inhibitors
FDA MoA N0000190108 Organic Anion Transporting Polypeptide 1B3 Inhibitors
FDA MoA N0000190113 Breast Cancer Resistance Protein Inhibitors
FDA EPC N0000191256 Hepatitis C Virus NS5A Inhibitor
CHEBI has role CHEBI:36044 anti-virus drug
CHEBI has role CHEBI:83799 hcv non-structural protein 5a inhibitor

Drug Use (View source of the data)

DiseaseRelationSNOMED_IDDOID
Chronic hepatitis C indication 128302006

Acid dissociation constants calculated using MoKa v3.0.0

Dissociation levelDissociation constantType (acidic/basic)
pKa1 12.05 acidic
pKa2 12.44 acidic
pKa3 12.88 acidic
pKa4 13.27 acidic
pKa5 6.51 Basic
pKa6 5.91 Basic

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
Potassium voltage-gated channel subfamily H member 2 Ion channel IC50 4.53 CHEMBL
Genome polyprotein Polyprotein INHIBITOR EC50 10.30 SCIENTIFIC LITERATURE SCIENTIFIC LITERATURE
Genome polyprotein Polyprotein INHIBITOR EC50 11.05 SCIENTIFIC LITERATURE SCIENTIFIC LITERATURE

External reference:

IDSource
D10065 KEGG_DRUG
4034682 VUID
N0000191739 NUI
1009119-65-6 SECONDARY_CAS_RN
4034682 VANDF
C2933824 UMLSCUI
CHEBI:82977 CHEBI
CHEMBL2023898 ChEMBL_ID
CHEMBL2303621 ChEMBL_ID
DB09102 DRUGBANK_ID
C549273 MESH_SUPPLEMENTAL_RECORD_UI
25154714 PUBCHEM_CID
11266 IUPHAR_LIGAND_ID
9483 INN_ID
LI2427F9CI UNII
1606217 RXNORM
229788 MMSL
30519 MMSL
d08285 MMSL
015679 NDDF
712519008 SNOMEDCT_US
714014007 SNOMEDCT_US

Pharmaceutical products:

None