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

Stem definitionDrug idCAS RN
histone deacetylase inhibitors 4124 149647-78-9

Description:

MoleculeDescription

Molfile Inchi Smiles

Synonyms:

  • vorinostat
  • suberoylanilide hydroxamic acid
A hydroxamic acid and anilide derivative that acts as a HISTONE DEACETYLASE inhibitor. It is used in the treatment of CUTANEOUS T-CELL LYMPHOMA and SEZARY SYNDROME.
  • Molecular weight: 264.33
  • Formula: C14H20N2O3
  • CLOGP: 0.99
  • LIPINSKI: 0
  • HAC: 5
  • HDO: 3
  • TPSA: 78.43
  • ALOGS: -3.57
  • ROTB: 8

  • Status: ONP

  • Legend:
    OFP - off patent
    OFM - off market
    ONP - on patent

Drug dosage:

None

ADMET properties:

PropertyValueReference
BDDCS (Biopharmaceutical Drug Disposition Classification System) 2 Hosey CM, Chan R, Benet LZ
BA (Bioavailability) 43 % Kim MT, Sedykh A, Chakravarti SK, Saiakhov RD, Zhu H
Vd (Volume of distribution) 0.50 L/kg Lombardo F, Berellini G, Obach RS
CL (Clearance) 28 mL/min/kg Lombardo F, Berellini G, Obach RS
fu (Fraction unbound in plasma) 0.29 % Lombardo F, Berellini G, Obach RS
t_half (Half-life) 0.76 hours Lombardo F, Berellini G, Obach RS

Approvals:

DateAgencyCompanyOrphan
Oct. 6, 2006 FDA MERCK

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
Febrile neutropenia 128.87 36.91 57 1093 94570 46590342
Dehydration 50.38 36.91 37 1113 159503 46525409
Cutaneous T-cell lymphoma 41.39 36.91 9 1141 1354 46683558
Platelet count decreased 40.37 36.91 27 1123 99997 46584915
Sepsis 37.23 36.91 29 1121 135985 46548927

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
Torsade de pointes 78.06 30.42 24 1431 7166 29943857
Lymphopenia 60.21 30.42 23 1432 13140 29937883
Febrile neutropenia 47.35 30.42 40 1415 106653 29844370
Electrocardiogram abnormal 40.81 30.42 14 1441 5878 29945145
Anaemia 35.83 30.42 47 1408 207945 29743078
Platelet count decreased 35.58 30.42 34 1421 106095 29844928
Cutaneous T-cell lymphoma 35.49 30.42 9 1446 1326 29949697
Activated partial thromboplastin time prolonged 33.35 30.42 13 1442 7815 29943208

Pharmacologic Action:

SourceCodeDescription
ATC L01XH01 ANTINEOPLASTIC AND IMMUNOMODULATING AGENTS
ANTINEOPLASTIC AGENTS
OTHER ANTINEOPLASTIC AGENTS
Histone deacetylase (HDAC) inhibitors
FDA MoA N0000175071 Histone Deacetylase Inhibitors
FDA EPC N0000175588 Histone Deacetylase Inhibitor
MeSH PA D000970 Antineoplastic Agents
MeSH PA D004791 Enzyme Inhibitors
MeSH PA D056572 Histone Deacetylase Inhibitors
CHEBI has role CHEBI:35610 cytostatic
CHEBI has role CHEBI:61115 hdac inhibitor
CHEBI has role CHEBI:68495 type i programmed cell-death inducer

Drug Use (View source of the data)

DiseaseRelationSNOMED_IDDOID
Primary cutaneous T-cell lymphoma indication 400122007
Hypocalcemia contraindication 5291005
Dehydration contraindication 34095006
Hypokalemia contraindication 43339004
Diarrhea contraindication 62315008
Diabetes mellitus contraindication 73211009 DOID:9351
Hyperglycemia contraindication 80394007 DOID:4195
Prolonged QT interval contraindication 111975006
Deep venous thrombosis contraindication 128053003
Hypomagnesemia contraindication 190855004
Pulmonary thromboembolism contraindication 233935004
Disease of liver contraindication 235856003 DOID:409
Anemia contraindication 271737000 DOID:2355
Pregnancy, function contraindication 289908002
Thrombocytopenic disorder contraindication 302215000 DOID:1588
Thromboembolic disorder contraindication 371039008
Breastfeeding (mother) contraindication 413712001
Vomiting contraindication 422400008
Congenital long QT syndrome contraindication 442917000

Acid dissociation constants calculated using MoKa v3.0.0

Dissociation levelDissociation constantType (acidic/basic)
pKa1 9.34 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
Histone deacetylase 1 Enzyme INHIBITOR Ki 8.89 CHEMBL CHEMBL
Histone deacetylase 2 Enzyme INHIBITOR Ki 8.80 CHEMBL CHEMBL
Histone deacetylase 6 Enzyme INHIBITOR Ki 9 CHEMBL CHEMBL
Histone deacetylase 3 Enzyme INHIBITOR Ki 8.30 CHEMBL CHEMBL
Histone deacetylase 11 Enzyme Ki 7.89 CHEMBL
Histone deacetylase Enzyme IC50 8 CHEMBL
Histone deacetylase 8 Enzyme Ki 6.76 CHEMBL
Histone deacetylase 1/3/5/8 Enzyme IC50 6.96 CHEMBL
Histone deacetylase 3/NCoR1 Transcription factor Ki 7.92 CHEMBL
Lysine-specific demethylase 4E Enzyme IC50 4.85 CHEMBL
Histone deacetylase 9 Enzyme Ki 7.31 CHEMBL
Histone deacetylase 4 Enzyme Ki 7.80 CHEMBL
Histone deacetylase 5 Enzyme Ki 7.48 CHEMBL
Histone deacetylase (HDAC1 and HDAC2) Enzyme IC50 8 CHEMBL
Histone deacetylase 3/Nuclear receptor corepressor 2 (HDAC3/NCoR2) Transcription factor Ki 8.70 CHEMBL
Histone deacetylase 7 Enzyme Ki 6.89 CHEMBL
Histone deacetylase 10 Enzyme Ki 7.30 CHEMBL
Histone deacetylase Enzyme IC50 7 CHEMBL
Histone deacetylase 1 Enzyme IC50 6.95 CHEMBL
Histone deacetylase Enzyme IC50 7.23 CHEMBL
HD2 type histone deacetylase HDA106; Histone deacetylase 2b; Uncharacterized protein Enzyme IC50 7.30 CHEMBL
Histone deacetylase Enzyme IC50 6.78 CHEMBL
Histone deacetylase-like amidohydrolase Enzyme Kd 6.52 CHEMBL
Histone deacetylase Enzyme IC50 7.55 CHEMBL

External reference:

IDSource
4025777 VUID
N0000179580 NUI
D06320 KEGG_DRUG
4025777 VANDF
C0672708 UMLSCUI
CHEBI:45716 CHEBI
SHH PDB_CHEM_ID
CHEMBL98 ChEMBL_ID
D000077337 MESH_DESCRIPTOR_UI
8661 INN_ID
DB02546 DRUGBANK_ID
58IFB293JI UNII
5311 PUBCHEM_CID
6852 IUPHAR_LIGAND_ID
194337 RXNORM
22259 MMSL
d05891 MMSL
011760 NDDF
422505001 SNOMEDCT_US
422523009 SNOMEDCT_US

Pharmaceutical products:

ProductCategoryIngredientsNDCFormQuantityRouteMarketingLabel
ZOLINZA HUMAN PRESCRIPTION DRUG LABEL 1 0006-0568 CAPSULE 100 mg ORAL NDA 30 sections