vorinostat 🐶 Veterinary Use | Indications/Contra | FAERs-F | FAERs-M | Orange Bk | PK/Tox | Related Drugs | 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
S (Water solubility) 0.07 mg/mL Bocci G, Oprea TI, Benet LZ

Predicted pharmacokinetic/toxicological properties (PK-AZ):

PropertyDescriptionValueUnitConfidenceSimilarity
azlogd74 LogD at pH 7.4 1.059 High 1
caco2-efflux Caco-2 efflux ratio (BA/AB) 1.371 High 1
caco2-intrinsic-papp Caco-2 intrinsic apparent permeability 15.311 10^-6 cm/s High 1
dh-clint Dog hepatocyte intrinsic clearance 43.451 uL/min/10^6 cells High 1
dppb Dog plasma protein binding (% unbound) 52.420 % High 1
fcs-ppb Fetal calf serum protein binding (% unbound) 53.330 % High 1
herg hERG pIC50 4.161 pIC50 High 1
hh-clint Human hepatocyte intrinsic clearance 35.563 uL/min/10^6 cells High 1
hlm-clint Human liver microsomal intrinsic clearance 4.295 uL/min/mg protein High 1
hppb Human plasma protein binding (% unbound) 43.480 % High 1
kinase-safety-class ACVR2A,ACVR2B,AURKA,AXL,BRAF,BTK,CAMK2B,CAMK2D,CDK5,CDK9,DDR1,DYRK1B,EGFR,EIF2AK3,EPHB4,ERBB2,FLT3,GRK2,ITK,JAK2,MAP2K6,MAP3K21,MAP3K7,MAPK14,MAPK7,MAPKAPK2,NTRK2,PDK1,PDK2,PDK4,PIK3CB,PRKDC,SIK2,SIK3,STK33,SYK,TEK,TTK 38
kinase-selectivity-class AXL,BRAF,DDR1,EIF2AK3,EPHB4,ERBB2,GRK2,MAP2K6,PDK4,STK33,TEK,TTK 12
mdck-mdr1-efflux MDCK-MDR1 efflux ratio 2.559 High 1
mh-clint Mouse hepatocyte intrinsic clearance 304.089 High 1
mppb Mouse plasma protein binding (% unbound) 56.980 High 1
nih-mdck-mdr1-efflux NIH MDCK-MDR1 efflux ratio 2.466 High 1
pfas-class PFAS structural alert (1 = True, 0 = False) 0
pld-class Phospholipidosis risk class (1 = positive, 0 = negative) 0 High 1
pppb Pig plasma protein binding (% unbound) 68.080 % High 1
rh-clint Rat hepatocyte intrinsic clearance 68.234 uL/min/10^6 cells High 1
rh-fuinc Rat hepatocyte fraction unbound in incubation 96.560 % High 1
rppb Rat plasma protein binding (% unbound) 46.550 % High 1
solubility-dd Solubility at pH 7.4 in DMSO 864.968 uM High 1

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 224.81 48.42 87 1378 158262 90468720
Electrocardiogram QT prolonged 99.38 48.42 39 1426 72417 90554565
Dehydration 62.80 48.42 39 1426 194408 90432574
Sepsis 57.88 48.42 36 1429 179778 90447204
Product use in unapproved indication 51.86 48.42 43 1422 336193 90290789

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 92.20 28.54 27 1626 8567 42611115
Lymphopenia 57.56 28.54 24 1629 21539 42598143
Febrile neutropenia 46.96 28.54 46 1607 185657 42434025
Product use in unapproved indication 39.87 28.54 42 1611 184414 42435268
Platelet count decreased 38.13 28.54 36 1617 138545 42481137
Electrocardiogram abnormal 36.46 28.54 14 1639 10131 42609551
Anaemia 36.10 28.54 49 1604 280229 42339453
Thrombocytopenia 30.30 28.54 37 1616 190242 42429440
Cutaneous T-cell lymphoma 29.19 28.54 8 1645 1990 42617692

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
Febrile neutropenia 143.93 34.82 94 2797 316673 110269735
Product use in unapproved indication 110.59 34.82 92 2799 447285 110139123
Torsade de pointes 92.52 34.82 31 2860 22569 110563839
Platelet count decreased 79.85 34.82 58 2833 230385 110356023
Cutaneous T-cell lymphoma 57.02 34.82 14 2877 3370 110583038
Thrombocytopenia 56.98 34.82 57 2834 348828 110237580
Malignant neoplasm progression 51.61 34.82 40 2851 174527 110411881
Sepsis 50.72 34.82 52 2839 327294 110259114
Acute myeloid leukaemia 50.28 34.82 23 2868 38087 110548321
Product administered to patient of inappropriate age 49.27 34.82 15 2876 8021 110578387
Dehydration 48.06 34.82 47 2844 279464 110306944
Anaemia 42.16 34.82 61 2830 547025 110039383
Lymphopenia 37.12 34.82 19 2872 40151 110546257

FDA Adverse Event Reporting System (Pediatric)

None

Pharmacologic Action:

SourceCodeDescription
ATC L01XH01 ANTINEOPLASTIC AND IMMUNOMODULATING AGENTS
ANTINEOPLASTIC AGENTS
OTHER ANTINEOPLASTIC AGENTS
Histone deacetylase (HDAC) inhibitors
FDA MoA N0000175071 Histone Deacetylase Inhibitors
MeSH PA D000970 Antineoplastic Agents
MeSH PA D004791 Enzyme Inhibitors
MeSH PA D056572 Histone Deacetylase Inhibitors
FDA EPC N0000175588 Histone Deacetylase Inhibitor
CHEBI has role CHEBI:35476 antipsychotic agent
CHEBI has role CHEBI:35610 antineoplastic agent
CHEBI has role CHEBI:61115 EC 3.5.1.98 (histone deacetylase) inhibitor
CHEBI has role CHEBI:64946 anti-HIV agent
CHEBI has role CHEBI:68495 apoptosis inducer
CHEBI has role CHEBI:75835 anti-anaemic agent

Related Drugs by ATC class:

L01XH Histone deacetylase (HDAC) inhibitors 4 drugs
belinostatpanobinostatromidepsintucidinostat

Drug Use | Suggest Off label Use Form| |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




🐶 Veterinary Drug Use

None

🐶 Veterinary products

None

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)

Formulation strengthTrade nameApplicantApplication numberApproval dateTypeDose formRoutePatent numberPatent expiration datePatent use
100MG ZOLINZA MSD SUB MERCK N021991 Oct. 6, 2006 RX CAPSULE ORAL 8450372 March 18, 2028 TREATMENT OF CUTANEOUS MANIFESTATIONS IN PATIENTS WITH CUTANEOUS T-CELL LYMPHOMA (CTCL)

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 3 Enzyme INHIBITOR Ki 8.30 CHEMBL CHEMBL
Histone deacetylase 6 Enzyme INHIBITOR Ki 9 CHEMBL CHEMBL
Histone deacetylase 2 Enzyme INHIBITOR Ki 8.80 CHEMBL CHEMBL
Serine/threonine-protein kinase PLK1 Kinase IC50 5.80 CHEMBL
Histone deacetylase 8 Enzyme Ki 6.76 CHEMBL
Histone deacetylase 4 Enzyme Ki 7.80 CHEMBL
Histone deacetylase 9 Enzyme Ki 7.31 CHEMBL
Leukotriene A-4 hydrolase Enzyme IC50 5.12 CHEMBL
Histone deacetylase 10 Enzyme Ki 7.30 CHEMBL
Histone deacetylase 11 Enzyme Ki 7.89 CHEMBL
Lysine-specific demethylase 4E Enzyme IC50 4.85 CHEMBL
Bromodomain-containing protein 4 Nuclear other IC50 8 CHEMBL
Histone deacetylase 3/Nuclear receptor corepressor 2 (HDAC3/NCoR2) Transcription factor Ki 8.70 CHEMBL
Histone deacetylase 3/NCoR1 Transcription factor Ki 7.92 CHEMBL
Histone deacetylase Enzyme IC50 8 CHEMBL
Histone deacetylase 1/3/5/8 Enzyme IC50 6.96 CHEMBL
Histone deacetylase (HDAC1 and HDAC2) Enzyme IC50 8 CHEMBL
Potassium voltage-gated channel subfamily H member 2 Ion channel IC50 6.49 CHEMBL
Epidermal growth factor receptor Kinase IC50 6.05 CHEMBL
Histone deacetylase 5 Enzyme Ki 7.48 CHEMBL
Histone deacetylase 7 Enzyme Ki 6.89 CHEMBL
HD2 type histone deacetylase HDA106; Histone deacetylase 2b; Uncharacterized protein Enzyme IC50 7.30 CHEMBL
Histone deacetylase 1 Enzyme IC50 6.95 CHEMBL
Histone deacetylase Enzyme IC50 7.55 CHEMBL
Histone deacetylase Enzyme IC50 7.23 CHEMBL
Histone deacetylase-like amidohydrolase Enzyme Kd 6.52 CHEMBL
Histone deacetylase Enzyme IC50 7 CHEMBL
Histone deacetylase Enzyme IC50 6.78 CHEMBL
Histone deacetylase 8 Enzyme IC50 6.23 CHEMBL
Leukotriene A-4 hydrolase Enzyme IC50 5.21 CHEMBL
Protein Tat Transcription factor EC50 5.64 CHEMBL

External reference:

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

Pharmaceutical products:

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