U.S. Department of Health & Human Services Divider Arrow National Institutes of Health Divider Arrow NCATS

Details

Stereochemistry ACHIRAL
Molecular Formula C14H20N2O3
Molecular Weight 264.3207
Optical Activity NONE
Defined Stereocenters 0 / 0
E/Z Centers 0
Charge 0

SHOW SMILES / InChI
Structure of VORINOSTAT

SMILES

C(CCCC(=NO)O)CCC(=Nc1ccccc1)O

InChI

InChIKey=WAEXFXRVDQXREF-UHFFFAOYSA-N
InChI=1S/C14H20N2O3/c17-13(15-12-8-4-3-5-9-12)10-6-1-2-7-11-14(18)16-19/h3-5,8-9,19H,1-2,6-7,10-11H2,(H,15,17)(H,16,18)

HIDE SMILES / InChI
Molecular Formula C14H20N2O3
Molecular Weight 264.3207
Charge 0
Count
Stereochemistry ACHIRAL
Additional Stereochemistry No
Defined Stereocenters 0 / 0
E/Z Centers 0
Optical Activity NONE

Description
Curator's Comment:: http://www.accessdata.fda.gov/drugsatfda_docs/label/2011/021991s002lbl.pdf

Vorinostat (rINN) or suberoylanilide hydroxamic acid (SAHA), is a drug currently under investigation for the treatment of cutaneous T cell lymphoma (CTCL). Vorinostat inhibits the enzymatic activity of histone deacetylases HDAC1, HDAC2 and HDAC3 (Class I) and HDAC6 (Class II) at nanomolar concentrations (IC50< 86 nM). These enzymes catalyze the removal of acetyl groups from the lysine residues of histones proteins. In some cancer cells, there is an overexpression of HDACs, or an aberrant recruitment of HDACs to oncogenic transcription factors causing hypoacetylation of core nucleosomal histones. By inhibiting histone deacetylase, vorinostat causes the accumulation of acetylated histones and induces cell cycle arrest and/or apoptosis of some transformed cells. The mechanism of the antineoplastic effect of vorinostat has not been fully characterized. Vorinostat is used for the treatment of cutaneous manifestations in patients with cutaneous T-cell lymphoma who have progressive, persistent or recurrent disease on or following two systemic therapies. Vorinostat is marketed under the name Zolinza by Merck for the treatment of cutaneous manifestations in patients with cutaneous T cell lymphoma (CTCL) when the disease persists, gets worse, or comes back during or after two systemic therapies.

CNS Activity

CNS Penetrant
2415
Curator's Comment:: Vorinostat was shown to cross the blood-brain barrier in a mouse model of Huntington's disease. It inhibited the growth of GL26 GBM cells implanted into the brains of mice. Vorinostat treatment induced accumulation of acetylated histones H2B, H3, and H4 in patients with recurrent GBM.

Originator

Approval Year

2006
63
Targets

Targets

Primary TargetPharmacologyConditionPotency
Inhibitor
7701
 0.119999999999999996 µM [IC50]
Inhibitor
7701
Cutaneous T-cell lymphoma
 0.130000000000000004 µM [IC50]
Inhibitor
7701
Cutaneous T-cell lymphoma
 0.149999999999999994 µM [IC50]
Inhibitor
7701
Cutaneous T-cell lymphoma
 0.280000000000000027 µM [IC50]
Inhibitor
7701
Cutaneous T-cell lymphoma
 1.67999999999999994 µM [IC50]
Inhibitor
7701
Cutaneous T-cell lymphoma
 57 nM [IC50]
Inhibitor
7701
Cutaneous T-cell lymphoma
 1 µM [EC50]
Conditions

Conditions

ConditionModalityTargetsHighest PhaseProduct
Primary
Histone deacetylase 6
NCI-H661
Histone deacetylase 1
Histone deacetylase 2
Histone deacetylase 8
Histone deacetylase 3
Approved
7997
Zolinza

Approved Use

Treatment of cutaneous manifestations in patients with cutaneous T cell lymphoma (CTCL) who have progressive, persistent or recurrent disease on or following two systemic therapies.

Launch Date

1160006400000
Cmax

Cmax

ValueDoseCo-administeredAnalytePopulation
1.2 μM
DRUG LABEL
https://www.accessdata.fda.gov/drugsatfda_docs/label/2011/021991s002lbl.pdf
400 mg single, oral
dose: 400 mg
route of administration: Oral
experiment type: SINGLE
co-administered:
VORINOSTAT plasma
Homo sapiens
population: UNHEALTHY
age: ADULT
sex: UNKNOWN
food status: HIGH-FAT
0.83 uM
Clinical Trial
https://clinicaltrials.gov/ct2/show/NCT00771472
400 mg single, oral
dose: 400 mg
route of administration: oral
experiment type: single
co-administered:
VORINOSTAT plasma
Homo sapiens
population: unhealthy
age:
sex:
food status:
1.17 uM
Clinical Trial
https://clinicaltrials.gov/ct2/show/NCT00771472
400 mg 1 times / day steady, oral
dose: 400 mg
route of administration: oral
experiment type: steady
co-administered:
VORINOSTAT plasma
Homo sapiens
population: unhealthy
age:
sex:
food status:
AUC

AUC

ValueDoseCo-administeredAnalytePopulation
5.5 μM × h
DRUG LABEL
https://www.accessdata.fda.gov/drugsatfda_docs/label/2011/021991s002lbl.pdf
400 mg single, oral
dose: 400 mg
route of administration: Oral
experiment type: SINGLE
co-administered:
VORINOSTAT plasma
Homo sapiens
population: UNHEALTHY
age: ADULT
sex: UNKNOWN
food status: HIGH-FAT
4.59 uM*h
Clinical Trial
https://clinicaltrials.gov/ct2/show/NCT00771472
400 mg single, oral
dose: 400 mg
route of administration: oral
experiment type: single
co-administered:
VORINOSTAT plasma
Homo sapiens
population: unhealthy
age:
sex:
food status:
5.59 uM*h
Clinical Trial
https://clinicaltrials.gov/ct2/show/NCT00771472
400 mg 1 times / day steady, oral
dose: 400 mg
route of administration: oral
experiment type: steady
co-administered:
VORINOSTAT plasma
Homo sapiens
population: unhealthy
age:
sex:
food status:
T1/2

T1/2

ValueDoseCo-administeredAnalytePopulation
2 h
DRUG LABEL
https://www.accessdata.fda.gov/drugsatfda_docs/label/2011/021991s002lbl.pdf
400 mg single, oral
dose: 400 mg
route of administration: Oral
experiment type: SINGLE
co-administered:
VORINOSTAT plasma
Homo sapiens
population: UNHEALTHY
age: ADULT
sex: UNKNOWN
food status: HIGH-FAT
1.94 h
Clinical Trial
https://clinicaltrials.gov/ct2/show/NCT00771472
400 mg single, oral
dose: 400 mg
route of administration: oral
experiment type: single
co-administered:
VORINOSTAT plasma
Homo sapiens
population: unhealthy
age:
sex:
food status:
2.3 h
Clinical Trial
https://clinicaltrials.gov/ct2/show/NCT00771472
400 mg 1 times / day steady, oral
dose: 400 mg
route of administration: oral
experiment type: steady
co-administered:
VORINOSTAT plasma
Homo sapiens
population: unhealthy
age:
sex:
food status:
Funbound

Funbound

ValueDoseCo-administeredAnalytePopulation
29%
DRUG LABEL
https://www.accessdata.fda.gov/drugsatfda_docs/label/2011/021991s002lbl.pdf
400 mg single, oral
dose: 400 mg
route of administration: Oral
experiment type: SINGLE
co-administered:
VORINOSTAT plasma
Homo sapiens
population: UNHEALTHY
age: ADULT
sex: UNKNOWN
food status: HIGH-FAT
Doses

Doses

DosePopulationAdverse events​
250 mg 2 times / day multiple, oral
Dose: 250 mg, 2 times / day
Route: oral
Route: multiple
Dose: 250 mg, 2 times / day
Sources:
https://pubmed.ncbi.nlm.nih.gov/18297527
unhealthy, 63 years (range: 38 - 74 years)
Health Status: unhealthy
Age Group: 63 years (range: 38 - 74 years)
Sources:
https://pubmed.ncbi.nlm.nih.gov/18297527
DLT: Fatigue...
Dose limiting toxicities:
Fatigue (grade 3, 1 patient)
Sources:
https://pubmed.ncbi.nlm.nih.gov/18297527
300 mg 2 times / day multiple, oral
Highest studied dose
Dose: 300 mg, 2 times / day
Route: oral
Route: multiple
Dose: 300 mg, 2 times / day
Sources:
https://www.accessdata.fda.gov/drugsatfda_docs/label/2006/021991lbl.pdf
https://pubmed.ncbi.nlm.nih.gov/16960145
unhealthy, 69 years (range: 26.0 - 80.0 years)
Health Status: unhealthy
Age Group: 69 years (range: 26.0 - 80.0 years)
Sex: M+F
Sources:
https://www.accessdata.fda.gov/drugsatfda_docs/label/2006/021991lbl.pdf
https://pubmed.ncbi.nlm.nih.gov/16960145
Disc. AE: Thrombocytopenia, Anemia...
Other AEs: Hypotension, Sepsis...
AEs leading to
discontinuation/dose reduction:
Thrombocytopenia (grade 3-4, 8%)
Anemia (grade 3-4, 17%)
Deep vein thrombosis (grade 3-4, 25%)
Pyrexia (grade 3-4, 25%)
Pulmonary embolism (grade 3-4, 17%)
Other AEs:
Hypotension (grade 3-4, 17%)
Sepsis (grade 3-4, 8%)
Fatigue (all grades, 27%)
Diarrhea (11%)
Nausea (8%)
Dysgeusia (11%)
Weight loss (3%)
Vomiting (11%)
Anorexia (3%)
Blood creatinine increased (8%)
Dehydration (5%)
Anemia (5%)
Sources:
https://www.accessdata.fda.gov/drugsatfda_docs/label/2006/021991lbl.pdf
https://pubmed.ncbi.nlm.nih.gov/16960145
AEs

AEs

AESignificanceDosePopulation
Fatigue grade 3, 1 patient
DLT, Disc. AE
250 mg 2 times / day multiple, oral
Dose: 250 mg, 2 times / day
Route: oral
Route: multiple
Dose: 250 mg, 2 times / day
Sources:
https://pubmed.ncbi.nlm.nih.gov/18297527
unhealthy, 63 years (range: 38 - 74 years)
Health Status: unhealthy
Age Group: 63 years (range: 38 - 74 years)
Sources:
https://pubmed.ncbi.nlm.nih.gov/18297527
Diarrhea 11%
300 mg 2 times / day multiple, oral
Highest studied dose
Dose: 300 mg, 2 times / day
Route: oral
Route: multiple
Dose: 300 mg, 2 times / day
Sources:
https://www.accessdata.fda.gov/drugsatfda_docs/label/2006/021991lbl.pdf
https://pubmed.ncbi.nlm.nih.gov/16960145
unhealthy, 69 years (range: 26.0 - 80.0 years)
Health Status: unhealthy
Age Group: 69 years (range: 26.0 - 80.0 years)
Sex: M+F
Sources:
https://www.accessdata.fda.gov/drugsatfda_docs/label/2006/021991lbl.pdf
https://pubmed.ncbi.nlm.nih.gov/16960145
Dysgeusia 11%
300 mg 2 times / day multiple, oral
Highest studied dose
Dose: 300 mg, 2 times / day
Route: oral
Route: multiple
Dose: 300 mg, 2 times / day
Sources:
https://www.accessdata.fda.gov/drugsatfda_docs/label/2006/021991lbl.pdf
https://pubmed.ncbi.nlm.nih.gov/16960145
unhealthy, 69 years (range: 26.0 - 80.0 years)
Health Status: unhealthy
Age Group: 69 years (range: 26.0 - 80.0 years)
Sex: M+F
Sources:
https://www.accessdata.fda.gov/drugsatfda_docs/label/2006/021991lbl.pdf
https://pubmed.ncbi.nlm.nih.gov/16960145
Vomiting 11%
300 mg 2 times / day multiple, oral
Highest studied dose
Dose: 300 mg, 2 times / day
Route: oral
Route: multiple
Dose: 300 mg, 2 times / day
Sources:
https://www.accessdata.fda.gov/drugsatfda_docs/label/2006/021991lbl.pdf
https://pubmed.ncbi.nlm.nih.gov/16960145
unhealthy, 69 years (range: 26.0 - 80.0 years)
Health Status: unhealthy
Age Group: 69 years (range: 26.0 - 80.0 years)
Sex: M+F
Sources:
https://www.accessdata.fda.gov/drugsatfda_docs/label/2006/021991lbl.pdf
https://pubmed.ncbi.nlm.nih.gov/16960145
Anorexia 3%
300 mg 2 times / day multiple, oral
Highest studied dose
Dose: 300 mg, 2 times / day
Route: oral
Route: multiple
Dose: 300 mg, 2 times / day
Sources:
https://www.accessdata.fda.gov/drugsatfda_docs/label/2006/021991lbl.pdf
https://pubmed.ncbi.nlm.nih.gov/16960145
unhealthy, 69 years (range: 26.0 - 80.0 years)
Health Status: unhealthy
Age Group: 69 years (range: 26.0 - 80.0 years)
Sex: M+F
Sources:
https://www.accessdata.fda.gov/drugsatfda_docs/label/2006/021991lbl.pdf
https://pubmed.ncbi.nlm.nih.gov/16960145
Weight loss 3%
300 mg 2 times / day multiple, oral
Highest studied dose
Dose: 300 mg, 2 times / day
Route: oral
Route: multiple
Dose: 300 mg, 2 times / day
Sources:
https://www.accessdata.fda.gov/drugsatfda_docs/label/2006/021991lbl.pdf
https://pubmed.ncbi.nlm.nih.gov/16960145
unhealthy, 69 years (range: 26.0 - 80.0 years)
Health Status: unhealthy
Age Group: 69 years (range: 26.0 - 80.0 years)
Sex: M+F
Sources:
https://www.accessdata.fda.gov/drugsatfda_docs/label/2006/021991lbl.pdf
https://pubmed.ncbi.nlm.nih.gov/16960145
Anemia 5%
300 mg 2 times / day multiple, oral
Highest studied dose
Dose: 300 mg, 2 times / day
Route: oral
Route: multiple
Dose: 300 mg, 2 times / day
Sources:
https://www.accessdata.fda.gov/drugsatfda_docs/label/2006/021991lbl.pdf
https://pubmed.ncbi.nlm.nih.gov/16960145
unhealthy, 69 years (range: 26.0 - 80.0 years)
Health Status: unhealthy
Age Group: 69 years (range: 26.0 - 80.0 years)
Sex: M+F
Sources:
https://www.accessdata.fda.gov/drugsatfda_docs/label/2006/021991lbl.pdf
https://pubmed.ncbi.nlm.nih.gov/16960145
Dehydration 5%
300 mg 2 times / day multiple, oral
Highest studied dose
Dose: 300 mg, 2 times / day
Route: oral
Route: multiple
Dose: 300 mg, 2 times / day
Sources:
https://www.accessdata.fda.gov/drugsatfda_docs/label/2006/021991lbl.pdf
https://pubmed.ncbi.nlm.nih.gov/16960145
unhealthy, 69 years (range: 26.0 - 80.0 years)
Health Status: unhealthy
Age Group: 69 years (range: 26.0 - 80.0 years)
Sex: M+F
Sources:
https://www.accessdata.fda.gov/drugsatfda_docs/label/2006/021991lbl.pdf
https://pubmed.ncbi.nlm.nih.gov/16960145
Blood creatinine increased 8%
300 mg 2 times / day multiple, oral
Highest studied dose
Dose: 300 mg, 2 times / day
Route: oral
Route: multiple
Dose: 300 mg, 2 times / day
Sources:
https://www.accessdata.fda.gov/drugsatfda_docs/label/2006/021991lbl.pdf
https://pubmed.ncbi.nlm.nih.gov/16960145
unhealthy, 69 years (range: 26.0 - 80.0 years)
Health Status: unhealthy
Age Group: 69 years (range: 26.0 - 80.0 years)
Sex: M+F
Sources:
https://www.accessdata.fda.gov/drugsatfda_docs/label/2006/021991lbl.pdf
https://pubmed.ncbi.nlm.nih.gov/16960145
Nausea 8%
300 mg 2 times / day multiple, oral
Highest studied dose
Dose: 300 mg, 2 times / day
Route: oral
Route: multiple
Dose: 300 mg, 2 times / day
Sources:
https://www.accessdata.fda.gov/drugsatfda_docs/label/2006/021991lbl.pdf
https://pubmed.ncbi.nlm.nih.gov/16960145
unhealthy, 69 years (range: 26.0 - 80.0 years)
Health Status: unhealthy
Age Group: 69 years (range: 26.0 - 80.0 years)
Sex: M+F
Sources:
https://www.accessdata.fda.gov/drugsatfda_docs/label/2006/021991lbl.pdf
https://pubmed.ncbi.nlm.nih.gov/16960145
Fatigue all grades, 27%
300 mg 2 times / day multiple, oral
Highest studied dose
Dose: 300 mg, 2 times / day
Route: oral
Route: multiple
Dose: 300 mg, 2 times / day
Sources:
https://www.accessdata.fda.gov/drugsatfda_docs/label/2006/021991lbl.pdf
https://pubmed.ncbi.nlm.nih.gov/16960145
unhealthy, 69 years (range: 26.0 - 80.0 years)
Health Status: unhealthy
Age Group: 69 years (range: 26.0 - 80.0 years)
Sex: M+F
Sources:
https://www.accessdata.fda.gov/drugsatfda_docs/label/2006/021991lbl.pdf
https://pubmed.ncbi.nlm.nih.gov/16960145
Hypotension grade 3-4, 17%
300 mg 2 times / day multiple, oral
Highest studied dose
Dose: 300 mg, 2 times / day
Route: oral
Route: multiple
Dose: 300 mg, 2 times / day
Sources:
https://www.accessdata.fda.gov/drugsatfda_docs/label/2006/021991lbl.pdf
https://pubmed.ncbi.nlm.nih.gov/16960145
unhealthy, 69 years (range: 26.0 - 80.0 years)
Health Status: unhealthy
Age Group: 69 years (range: 26.0 - 80.0 years)
Sex: M+F
Sources:
https://www.accessdata.fda.gov/drugsatfda_docs/label/2006/021991lbl.pdf
https://pubmed.ncbi.nlm.nih.gov/16960145
Anemia grade 3-4, 17%
Disc. AE
300 mg 2 times / day multiple, oral
Highest studied dose
Dose: 300 mg, 2 times / day
Route: oral
Route: multiple
Dose: 300 mg, 2 times / day
Sources:
https://www.accessdata.fda.gov/drugsatfda_docs/label/2006/021991lbl.pdf
https://pubmed.ncbi.nlm.nih.gov/16960145
unhealthy, 69 years (range: 26.0 - 80.0 years)
Health Status: unhealthy
Age Group: 69 years (range: 26.0 - 80.0 years)
Sex: M+F
Sources:
https://www.accessdata.fda.gov/drugsatfda_docs/label/2006/021991lbl.pdf
https://pubmed.ncbi.nlm.nih.gov/16960145
Pulmonary embolism grade 3-4, 17%
Disc. AE
300 mg 2 times / day multiple, oral
Highest studied dose
Dose: 300 mg, 2 times / day
Route: oral
Route: multiple
Dose: 300 mg, 2 times / day
Sources:
https://www.accessdata.fda.gov/drugsatfda_docs/label/2006/021991lbl.pdf
https://pubmed.ncbi.nlm.nih.gov/16960145
unhealthy, 69 years (range: 26.0 - 80.0 years)
Health Status: unhealthy
Age Group: 69 years (range: 26.0 - 80.0 years)
Sex: M+F
Sources:
https://www.accessdata.fda.gov/drugsatfda_docs/label/2006/021991lbl.pdf
https://pubmed.ncbi.nlm.nih.gov/16960145
Deep vein thrombosis grade 3-4, 25%
Disc. AE
300 mg 2 times / day multiple, oral
Highest studied dose
Dose: 300 mg, 2 times / day
Route: oral
Route: multiple
Dose: 300 mg, 2 times / day
Sources:
https://www.accessdata.fda.gov/drugsatfda_docs/label/2006/021991lbl.pdf
https://pubmed.ncbi.nlm.nih.gov/16960145
unhealthy, 69 years (range: 26.0 - 80.0 years)
Health Status: unhealthy
Age Group: 69 years (range: 26.0 - 80.0 years)
Sex: M+F
Sources:
https://www.accessdata.fda.gov/drugsatfda_docs/label/2006/021991lbl.pdf
https://pubmed.ncbi.nlm.nih.gov/16960145
Pyrexia grade 3-4, 25%
Disc. AE
300 mg 2 times / day multiple, oral
Highest studied dose
Dose: 300 mg, 2 times / day
Route: oral
Route: multiple
Dose: 300 mg, 2 times / day
Sources:
https://www.accessdata.fda.gov/drugsatfda_docs/label/2006/021991lbl.pdf
https://pubmed.ncbi.nlm.nih.gov/16960145
unhealthy, 69 years (range: 26.0 - 80.0 years)
Health Status: unhealthy
Age Group: 69 years (range: 26.0 - 80.0 years)
Sex: M+F
Sources:
https://www.accessdata.fda.gov/drugsatfda_docs/label/2006/021991lbl.pdf
https://pubmed.ncbi.nlm.nih.gov/16960145
Sepsis grade 3-4, 8%
300 mg 2 times / day multiple, oral
Highest studied dose
Dose: 300 mg, 2 times / day
Route: oral
Route: multiple
Dose: 300 mg, 2 times / day
Sources:
https://www.accessdata.fda.gov/drugsatfda_docs/label/2006/021991lbl.pdf
https://pubmed.ncbi.nlm.nih.gov/16960145
unhealthy, 69 years (range: 26.0 - 80.0 years)
Health Status: unhealthy
Age Group: 69 years (range: 26.0 - 80.0 years)
Sex: M+F
Sources:
https://www.accessdata.fda.gov/drugsatfda_docs/label/2006/021991lbl.pdf
https://pubmed.ncbi.nlm.nih.gov/16960145
Thrombocytopenia grade 3-4, 8%
Disc. AE
300 mg 2 times / day multiple, oral
Highest studied dose
Dose: 300 mg, 2 times / day
Route: oral
Route: multiple
Dose: 300 mg, 2 times / day
Sources:
https://www.accessdata.fda.gov/drugsatfda_docs/label/2006/021991lbl.pdf
https://pubmed.ncbi.nlm.nih.gov/16960145
unhealthy, 69 years (range: 26.0 - 80.0 years)
Health Status: unhealthy
Age Group: 69 years (range: 26.0 - 80.0 years)
Sex: M+F
Sources:
https://www.accessdata.fda.gov/drugsatfda_docs/label/2006/021991lbl.pdf
https://pubmed.ncbi.nlm.nih.gov/16960145
Overview

Overview

CYP3A4CYP2C9CYP2D6hERG
inhibitor
1172

inducer
657

supressor
17
inhibitor
1318

inducer
343
inhibitor
1421
inhibitor
1360

OverviewOther

Other InhibitorOther SubstrateOther Inducer
CYP
97

P-gp
1089

CYP1A2
1268

CYP2B6
679

CYP2C8
761

CYP2C19
1215
CYP
231

P-gp
1223

UGT1A1
358

UGT1A3
358

UGT1A7
197

UGT1A8
242

UGT1A9
327

UGT2B7
329

UGT2B17
184
CYP1A2
618

CYP2B6
486

CYP2C19
260
Drug as perpetrator​

Drug as perpetrator​

TargetModalityActivityMetaboliteClinical evidence
P-gp
1255
 inconclusive
no (co-administration study)
Comment: vorinostat has no inhibitory effect on the tranport of vinblastine
Page: 4, 6, 27
CYP2C19
1277
 no [IC50 79.8 uM]
CYP1A2
1406
 no [IC50 >100 uM]
CYP2B6
845
 no [IC50 >100 uM]
CYP2C8
810
 no [IC50 >100 uM]
CYP2C9
1362
 no [IC50 >100 uM]
CYP2D6
1455
 no [IC50 >100 uM]
CYP3A4
1462
 no [IC50 >100 uM]
CYP
131
 no
CYP1A2
1406
 yes
CYP2B6
845
 yes
CYP2C19
1277
 yes
CYP2C9
1362
 yes
CYP3A4
1462
 yes
CYP3A4
1462
 yes
Drug as victim

Drug as victim

TargetModalityActivityMetaboliteClinical evidence
P-gp
1223
 inconclusive
CYP
231
 no
UGT1A1
358
 yes
UGT1A3
358
 yes
UGT1A7
197
 yes
UGT1A8
242
 yes
UGT1A9
327
 yes
UGT2B17
184
 yes
UGT2B7
329
 yes
Tox targets

Tox targets

TargetModalityActivityMetaboliteClinical evidence
hERG
1392
Sourcing

Sourcing

Vendor/AggregatorIDURL
ChEBI
CHEBI:45716
https://www.ebi.ac.uk/chebi/searchId.do?chebiId=CHEBI:45716
MolPort
MolPort-003-850-293
https://www.molport.com/shop/molecule-link/MolPort-003-850-293
ZINC
ZINC000001543873
http://zinc15.docking.org/substances/ZINC000001543873
PubMed

PubMed

TitleDatePubMed
Histone deacetylase inhibitors up-regulate the expression of tight junction proteins.
2004 Dec
The histone deacetylase inhibitor suberoylanilide hydroxamic acid induces apoptosis via induction of 15-lipoxygenase-1 in colorectal cancer cells.
2004 Dec 1
Proteasome inhibition sensitizes non-small cell lung cancer to histone deacetylase inhibitor-induced apoptosis through the generation of reactive oxygen species.
2004 Nov
Modulation of renal disease in MRL/lpr mice by suberoylanilide hydroxamic acid.
2004 Sep 15
High turbulence liquid chromatography online extraction and tandem mass spectrometry for the simultaneous determination of suberoylanilide hydroxamic acid and its two metabolites in human serum.
2005
Histone deacetylase inhibitors in programmed cell death and cancer therapy.
2005 Apr
Cotreatment with suberanoylanilide hydroxamic acid and 17-allylamino 17-demethoxygeldanamycin synergistically induces apoptosis in Bcr-Abl+ Cells sensitive and resistant to STI571 (imatinib mesylate) in association with down-regulation of Bcr-Abl, abrogation of signal transducer and activator of transcription 5 activity, and Bax conformational change.
2005 Apr
Suberoylanilide hydroxamic acid combined with gemcitabine enhances apoptosis in non-small cell lung cancer.
2005 Aug
Synergistic apoptosis induction by proteasome and histone deacetylase inhibitors is dependent on protein synthesis.
2005 Aug
Histone deacetylase inhibitors induced caspase-independent apoptosis in human pancreatic adenocarcinoma cell lines.
2005 Aug
It's about time: scheduling alters effect of histone deacetylase inhibitors on camptothecin-treated cells.
2005 Aug 1
Histone deacetylase inhibitors induce differentiation of human endometrial adenocarcinoma cells through up-regulation of glycodelin.
2005 Dec
Novel inhibitors of human histone deacetylases: design, synthesis, enzyme inhibition, and cancer cell growth inhibition of SAHA-based non-hydroxamates.
2005 Feb 24
Histone deacetylase inhibitors profoundly decrease proliferation of human lymphoid cancer cell lines.
2005 Jan
The histone deacetylase inhibitor suberoylanilide hydroxamic acid down-regulates expression levels of Bcr-abl, c-Myc and HDAC3 in chronic myeloid leukemia cell lines.
2005 Jan
Identification of a potent non-hydroxamate histone deacetylase inhibitor by mechanism-based drug design.
2005 Jan 17
Interactive effects of HDAC inhibitors and TRAIL on apoptosis are associated with changes in mitochondrial functions and expressions of cell cycle regulatory genes in multiple myeloma.
2005 Jul
Blockade of histone deacetylase inhibitor-induced RelA/p65 acetylation and NF-kappaB activation potentiates apoptosis in leukemia cells through a process mediated by oxidative damage, XIAP downregulation, and c-Jun N-terminal kinase 1 activation.
2005 Jul
Effect of inhibitors of histone deacetylase on the induction of cell differentiation in murine and human erythroleukemia cell lines.
2005 Jul
Design and synthesis of non-hydroxamate histone deacetylase inhibitors: identification of a selective histone acetylating agent.
2005 Jul 1
A new simple and high-yield synthesis of suberoylanilide hydroxamic acid and its inhibitory effect alone or in combination with retinoids on proliferation of human prostate cancer cells.
2005 Jul 28
The histone-deacetylase inhibitor SAHA potentiates proapoptotic effects of 5-fluorouracil and irinotecan in hepatoma cells.
2005 Jun
Phase I study of an oral histone deacetylase inhibitor, suberoylanilide hydroxamic acid, in patients with advanced cancer.
2005 Jun 10
Drug insight: Histone deacetylase inhibitors--development of the new targeted anticancer agent suberoylanilide hydroxamic acid.
2005 Mar
4-Hydroxybenzoyl derivative from the aqueous extract of the hydroid Campanularia sp.
2005 Mar
Histone deacetylase inhibitors interact synergistically with tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) to induce apoptosis in carcinoma cell lines.
2005 Mar
Effects of suberoylanilide hydroxamic acid and trichostatin A on induction of cytochrome P450 enzymes and benzo[a]pyrene DNA adduct formation in human cells.
2005 Mar 1
[Histone deacetylase inhibitors as a new generation of anti-cancer agents].
2005 Mar 11
Coadministration of histone deacetylase inhibitors and perifosine synergistically induces apoptosis in human leukemia cells through Akt and ERK1/2 inactivation and the generation of ceramide and reactive oxygen species.
2005 Mar 15
Suberoylanilide hydroxamic acid (SAHA) has potent anti-glioma properties in vitro, ex vivo and in vivo.
2005 May
Modulation of radiation response by histone deacetylase inhibition.
2005 May 1
The role of histone acetylation in SMN gene expression.
2005 May 1
Novel histone deacetylase inhibitors in the treatment of thyroid cancer.
2005 May 15
Selective induction of apoptosis by histone deacetylase inhibitor SAHA in cutaneous T-cell lymphoma cells: relevance to mechanism of therapeutic action.
2005 Nov
Suberoylanilide hydroxamic acid enhances gap junctional intercellular communication via acetylation of histone containing connexin 43 gene locus.
2005 Nov 1
Histone deacetylases in acute myeloid leukaemia show a distinctive pattern of expression that changes selectively in response to deacetylase inhibitors.
2005 Oct
Early clinical data and potential clinical utility of novel histone deacetylase inhibitors in prostate cancer.
2005 Sep
Synergistic interactions between MEK1/2 and histone deacetylase inhibitors in BCR/ABL+ human leukemia cells.
2005 Sep
Activity of suberoylanilide hydroxamic Acid against human breast cancer cells with amplification of her-2.
2005 Sep 1
Induction of polyploidy by histone deacetylase inhibitor: a pathway for antitumor effects.
2005 Sep 1
Histone deacetylase inhibitors suppress the induction of c-Jun and its target genes including COX-2.
2005 Sep 23
Loss of interleukin-2-dependency in HTLV-I-infected T cells on gene silencing of thioredoxin-binding protein-2.
2006 Apr 6
Histone deacetylase inhibitors reduce VEGF production and induce growth suppression and apoptosis in human mantle cell lymphoma.
2006 Jan
SAHA, a HDAC inhibitor, has profound anti-growth activity against non-small cell lung cancer cells.
2006 Jan
5-Aza-2'-deoxycytidine (decitabine) can relieve p21WAF1 repression in human acute myeloid leukemia by a mechanism involving release of histone deacetylase 1 (HDAC1) without requiring p21WAF1 promoter demethylation.
2006 Jan
Clinical experience with intravenous and oral formulations of the novel histone deacetylase inhibitor suberoylanilide hydroxamic acid in patients with advanced hematologic malignancies.
2006 Jan 1
SAHA-sensitized prostate cancer cells to TNFalpha-related apoptosis-inducing ligand (TRAIL): mechanisms leading to synergistic apoptosis.
2006 Jul 1
Histone deacetylase inhibitors induce cell death and enhance the susceptibility to ionizing radiation, etoposide, and TRAIL in medulloblastoma cells.
2006 Mar
Suberoylanilide hydroxamic acid potentiates apoptosis, inhibits invasion, and abolishes osteoclastogenesis by suppressing nuclear factor-kappaB activation.
2006 Mar 3
Carbonyl- and sulfur-containing analogs of suberoylanilide hydroxamic acid: Potent inhibition of histone deacetylases.
2006 May 15
Patents

Patents

JP2009073834A
1
JP2011506455A
48

Sample Use Guides

In Vivo Use Guide
400 mg orally once daily with food.
Route of Administration: Oral
In Vitro Use Guide
Concentrations of vorinostat higher than 0.5 uM significantly inhibited the upregulated gene expression of MMP-1 and MMP-13 induced by IL-1β, whereas 0.1 uM vorinostat showed no obvious effect. Conversely, 0.5 uM vorinostat or higher concentration increased the TIMP-1 expression.
Substance Class Chemical
Created
by admin
on Fri Jun 25 22:11:30 UTC 2021
Edited
by admin
on Fri Jun 25 22:11:30 UTC 2021
Record UNII
58IFB293JI
Record Status Validated (UNII)
Record Version
  • Download
Name Type Language
VORINOSTAT
INN   JAN   MART.   MI   ORANGE BOOK   USAN   VANDF   WHO-DD  
INN   USAN  
Official Name English
VORINOSTAT [MI]
Common Name English
NSC-759852
Code English
VORINOSTAT [ORANGE BOOK]
Common Name English
NSC-701852
Code English
N-HYDROXY-N'-PHENYLOCTANEDIAMIDE
Systematic Name English
NSC-748799
Code English
ZOLINZA
Brand Name English
VORINOSTAT [WHO-DD]
Common Name English
MK0683
Code English
VORINOSTAT [MART.]
Common Name English
MK-0683
Code English
VORINOSTAT [USAN]
Common Name English
OCTANEDIAMIDE, N-HYDROXY-N'-PHENYL-
Systematic Name English
VORINOSTAT [INN]
Common Name English
SUBEROYLANILIDE HYDROXAMIC ACID
Common Name English
VORINOSTAT [JAN]
Common Name English
VORINOSTAT [VANDF]
Common Name English
Classification Tree Code System Code
FDA ORPHAN DRUG 177203
Created by admin on Fri Jun 25 22:11:31 UTC 2021 , Edited by admin on Fri Jun 25 22:11:31 UTC 2021
WHO-VATC QL01XX38
Created by admin on Fri Jun 25 22:11:31 UTC 2021 , Edited by admin on Fri Jun 25 22:11:31 UTC 2021
EU-Orphan Drug EU/3/11/854
Created by admin on Fri Jun 25 22:11:31 UTC 2021 , Edited by admin on Fri Jun 25 22:11:31 UTC 2021
LIVERTOX 1040
Created by admin on Fri Jun 25 22:11:31 UTC 2021 , Edited by admin on Fri Jun 25 22:11:31 UTC 2021
NCI_THESAURUS C1946
Created by admin on Fri Jun 25 22:11:31 UTC 2021 , Edited by admin on Fri Jun 25 22:11:31 UTC 2021
NDF-RT N0000175588
Created by admin on Fri Jun 25 22:11:31 UTC 2021 , Edited by admin on Fri Jun 25 22:11:31 UTC 2021
FDA ORPHAN DRUG 540116
Created by admin on Fri Jun 25 22:11:31 UTC 2021 , Edited by admin on Fri Jun 25 22:11:31 UTC 2021
WHO-ATC L01XX38
Created by admin on Fri Jun 25 22:11:31 UTC 2021 , Edited by admin on Fri Jun 25 22:11:31 UTC 2021
NDF-RT N0000175071
Created by admin on Fri Jun 25 22:11:31 UTC 2021 , Edited by admin on Fri Jun 25 22:11:31 UTC 2021
FDA ORPHAN DRUG 174203
Created by admin on Fri Jun 25 22:11:31 UTC 2021 , Edited by admin on Fri Jun 25 22:11:31 UTC 2021
FDA ORPHAN DRUG 169503
Created by admin on Fri Jun 25 22:11:31 UTC 2021 , Edited by admin on Fri Jun 25 22:11:31 UTC 2021
Code System Code Type Description
ChEMBL
CHEMBL98
Created by admin on Fri Jun 25 22:11:31 UTC 2021 , Edited by admin on Fri Jun 25 22:11:31 UTC 2021
PRIMARY
DRUG CENTRAL
4124
Created by admin on Fri Jun 25 22:11:31 UTC 2021 , Edited by admin on Fri Jun 25 22:11:31 UTC 2021
PRIMARY
CAS
149647-78-9
Created by admin on Fri Jun 25 22:11:31 UTC 2021 , Edited by admin on Fri Jun 25 22:11:31 UTC 2021
PRIMARY
MERCK INDEX
M11502
Created by admin on Fri Jun 25 22:11:31 UTC 2021 , Edited by admin on Fri Jun 25 22:11:31 UTC 2021
PRIMARY Merck Index
HSDB
7930
Created by admin on Fri Jun 25 22:11:31 UTC 2021 , Edited by admin on Fri Jun 25 22:11:31 UTC 2021
PRIMARY
PUBCHEM
5311
Created by admin on Fri Jun 25 22:11:31 UTC 2021 , Edited by admin on Fri Jun 25 22:11:31 UTC 2021
PRIMARY
RXCUI
194337
Created by admin on Fri Jun 25 22:11:31 UTC 2021 , Edited by admin on Fri Jun 25 22:11:31 UTC 2021
PRIMARY RxNorm
FDA UNII
58IFB293JI
Created by admin on Fri Jun 25 22:11:31 UTC 2021 , Edited by admin on Fri Jun 25 22:11:31 UTC 2021
PRIMARY
MESH
C111237
Created by admin on Fri Jun 25 22:11:31 UTC 2021 , Edited by admin on Fri Jun 25 22:11:31 UTC 2021
PRIMARY
INN
8661
Created by admin on Fri Jun 25 22:11:31 UTC 2021 , Edited by admin on Fri Jun 25 22:11:31 UTC 2021
PRIMARY
NCI_THESAURUS
C1796
Created by admin on Fri Jun 25 22:11:31 UTC 2021 , Edited by admin on Fri Jun 25 22:11:31 UTC 2021
PRIMARY
IUPHAR
6852
Created by admin on Fri Jun 25 22:11:31 UTC 2021 , Edited by admin on Fri Jun 25 22:11:31 UTC 2021
PRIMARY
WIKIPEDIA
VORINOSTAT
Created by admin on Fri Jun 25 22:11:31 UTC 2021 , Edited by admin on Fri Jun 25 22:11:31 UTC 2021
PRIMARY
EPA CompTox
149647-78-9
Created by admin on Fri Jun 25 22:11:31 UTC 2021 , Edited by admin on Fri Jun 25 22:11:31 UTC 2021
PRIMARY
EVMPD
SUB23356
Created by admin on Fri Jun 25 22:11:31 UTC 2021 , Edited by admin on Fri Jun 25 22:11:31 UTC 2021
PRIMARY
DRUG BANK
DB02546
Created by admin on Fri Jun 25 22:11:31 UTC 2021 , Edited by admin on Fri Jun 25 22:11:31 UTC 2021
PRIMARY
Related Record Type Details
HISTONE DEACETYLASE 1
TARGET -> INHIBITOR
BINDING
IC50
HISTONE DEACETYLASE 6
TARGET -> INHIBITOR
BINDING
IC50
URIDINE DIPHOSPHATE GLUCURONOSYLTRANSFERASE 1A1
METABOLIC ENZYME -> SUBSTRATE
Structure of VORINOSTAT
EXCRETED UNCHANGED
AMOUNT EXCRETED
URINE
HISTONE DEACETYLASE 2
TARGET -> INHIBITOR
BINDING
IC50
HISTONE DEACETYLASE 8
TARGET -> INHIBITOR
BINDING
IC50
URIDINE DIPHOSPHATE GLUCURONOSYLTRANSFERASE 2B17
METABOLIC ENZYME -> SUBSTRATE
HISTONE DEACETYLASE 5
TARGET -> INHIBITOR
BINDING
IC50
URIDINE DIPHOSPHATE GLUCURONOSYLTRANSFERASE 1A7
METABOLIC ENZYME -> SUBSTRATE
URIDINE DIPHOSPHATE GLUCURONOSYLTRANSFERASE 1A9
METABOLIC ENZYME -> SUBSTRATE
URIDINE DIPHOSPHATE GLUCURONOSYLTRANSFERASE 1A3
METABOLIC ENZYME -> SUBSTRATE
PLASMA PROTEIN FRACTION (HUMAN)
BINDER->LIGAND
BINDING
HUMAN IMMUNODEFICIENCY VIRUS TYPE 1
TARGET ORGANISM->INHIBITOR
URIDINE DIPHOSPHATE GLUCURONOSYLTRANSFERASE 1A8
METABOLIC ENZYME -> SUBSTRATE
HISTONE DEACETYLASE 3
TARGET -> INHIBITOR
BINDING
IC50
URIDINE DIPHOSPHATE GLUCURONOSYLTRANSFERASE 2B7
METABOLIC ENZYME -> SUBSTRATE
Related Record Type Details
Structure of N-PHENYLOCTANEDIAMIDE
METABOLITE -> PARENT
Structure of SUBERANILIC ACID
METABOLITE -> PARENT
Structure of 4-AMINOPHENYL SULFATE
METABOLITE -> PARENT
Structure of ACETAMINOPHEN SULFATE
METABOLITE -> PARENT
Structure of 2-AMINOPHENYL SULFATE
METABOLITE -> PARENT
Structure of SUCCINANILIC ACID
METABOLITE INACTIVE -> PARENT
PLASMA
Structure of ADIPANILIC ACID
METABOLITE -> PARENT
Structure of VORINOSTAT-O-GLUCURONIDE
METABOLITE INACTIVE -> PARENT
MAJOR
URINE
Structure of ACETANILIDE
METABOLITE -> PARENT
Structure of SUCCINANILIC ACID
METABOLITE INACTIVE -> PARENT
URINE
Structure of ACETAMINOPHEN
METABOLITE -> PARENT
Related Record Type Details
Structure of VORINOSTAT
ACTIVE MOIETY
Name Property Type Amount Referenced Substance Defining Parameters References
blood-to-plasma ratio PHARMACOKINETIC
Tmax PHARMACOKINETIC FED CONDITION

HIGH-FAT MEAL

Volume of Distribution PHARMACOKINETIC INTRAVENOUS ADMINISTRATION

DOSE

Biological Half-life PHARMACOKINETIC
Tmax PHARMACOKINETIC ORAL ADMINISTRATION

FASTED CONDITION

NIH
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