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

Details

Stereochemistry ACHIRAL
Molecular Formula C14H20N2O3
Molecular Weight 264.3202
Optical Activity NONE
Defined Stereocenters 0 / 0
E/Z Centers 0
Charge 0

SHOW SMILES / InChI
Structure of VORINOSTAT

SMILES

ONC(=O)CCCCCCC(=O)NC1=CC=CC=C1

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 264.3202
Charge 0
Count
Stereochemistry ACHIRAL
Additional Stereochemistry
Defined Stereocenters 0 / 0
E/Z Centers 0
Optical Activity NONE

Description

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

Approval Year

PubMed

PubMed

TitleDatePubMed
Novel mechanisms of apoptosis induced by histone deacetylase inhibitors.
2003 Aug 1
Gateways to clinical trials.
2003 Dec
Simultaneous activation of the intrinsic and extrinsic pathways by histone deacetylase (HDAC) inhibitors and tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) synergistically induces mitochondrial damage and apoptosis in human leukemia cells.
2003 Dec
Coadministration of the heat shock protein 90 antagonist 17-allylamino- 17-demethoxygeldanamycin with suberoylanilide hydroxamic acid or sodium butyrate synergistically induces apoptosis in human leukemia cells.
2003 Dec 1
Inhibition of histone deacetylase increases cytotoxicity to anticancer drugs targeting DNA.
2003 Nov 1
The proteasome inhibitor bortezomib interacts synergistically with histone deacetylase inhibitors to induce apoptosis in Bcr/Abl+ cells sensitive and resistant to STI571.
2003 Nov 15
Microarray profiling of the effects of histone deacetylase inhibitors on gene expression in cancer cell lines.
2004 Apr
The histone deacetylase inhibitor suberoylanilide hydroxamic acid induces apoptosis via induction of 15-lipoxygenase-1 in colorectal cancer cells.
2004 Dec 1
QSAR studies of PC-3 cell line inhibition activity of TSA and SAHA-like hydroxamic acids.
2004 Feb 9
Suberanilohydroxamic Acid. Aton Pharma.
2004 Jul
Requirement of histone deacetylase activity for signaling by STAT1.
2004 Jul 16
Thiol-based SAHA analogues as potent histone deacetylase inhibitors.
2004 Jun 21
Role of oxidative enzymatic treatments on enzymatic hydrolysis of softwood.
2004 Jun 5
Silent advances.
2004 Mar
The mechanism of the anti-tumor activity of the histone deacetylase inhibitor, suberoylanilide hydroxamic acid (SAHA).
2004 May
Sequence-specific potentiation of topoisomerase II inhibitors by the histone deacetylase inhibitor suberoylanilide hydroxamic acid.
2004 May 15
Proteasome inhibition sensitizes non-small cell lung cancer to histone deacetylase inhibitor-induced apoptosis through the generation of reactive oxygen species.
2004 Nov
Contribution of disruption of the nuclear factor-kappaB pathway to induction of apoptosis in human leukemia cells by histone deacetylase inhibitors and flavopiridol.
2004 Oct
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
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
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
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
The role of histone acetylation in SMN gene expression.
2005 May 1
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
Crystal structure of a bacterial class 2 histone deacetylase homologue.
2005 Nov 18
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

Sample Use Guides

In Vivo Use Guide
400 mg orally once daily with food. If patient is intolerant to therapy, the dose may be reduced to 300 mg orally once daily with food. If necessary, the dose may be further reduced to 300 mg once daily with food for 5 consecutive days each week.
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 Mon Oct 21 20:47:06 UTC 2019
Edited
by admin
on Mon Oct 21 20:47:06 UTC 2019
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
VORINOSTAT [ORANGE BOOK]
Common Name English
N-HYDROXY-N'-PHENYLOCTANEDIAMIDE
Systematic Name 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 Mon Oct 21 20:47:06 UTC 2019 , Edited by admin on Mon Oct 21 20:47:06 UTC 2019
WHO-VATC QL01XX38
Created by admin on Mon Oct 21 20:47:07 UTC 2019 , Edited by admin on Mon Oct 21 20:47:07 UTC 2019
EU-Orphan Drug EU/3/11/854
Created by admin on Mon Oct 21 20:47:06 UTC 2019 , Edited by admin on Mon Oct 21 20:47:06 UTC 2019
LIVERTOX 1040
Created by admin on Mon Oct 21 20:47:07 UTC 2019 , Edited by admin on Mon Oct 21 20:47:07 UTC 2019
NCI_THESAURUS C1946
Created by admin on Mon Oct 21 20:47:06 UTC 2019 , Edited by admin on Mon Oct 21 20:47:06 UTC 2019
NDF-RT N0000175588
Created by admin on Mon Oct 21 20:47:07 UTC 2019 , Edited by admin on Mon Oct 21 20:47:07 UTC 2019
FDA ORPHAN DRUG 540116
Created by admin on Mon Oct 21 20:47:06 UTC 2019 , Edited by admin on Mon Oct 21 20:47:06 UTC 2019
WHO-ATC L01XX38
Created by admin on Mon Oct 21 20:47:07 UTC 2019 , Edited by admin on Mon Oct 21 20:47:07 UTC 2019
NDF-RT N0000175071
Created by admin on Mon Oct 21 20:47:07 UTC 2019 , Edited by admin on Mon Oct 21 20:47:07 UTC 2019
FDA ORPHAN DRUG 174203
Created by admin on Mon Oct 21 20:47:06 UTC 2019 , Edited by admin on Mon Oct 21 20:47:06 UTC 2019
FDA ORPHAN DRUG 169503
Created by admin on Mon Oct 21 20:47:06 UTC 2019 , Edited by admin on Mon Oct 21 20:47:06 UTC 2019
Code System Code Type Description
ChEMBL
CHEMBL98
Created by admin on Mon Oct 21 20:47:06 UTC 2019 , Edited by admin on Mon Oct 21 20:47:06 UTC 2019
PRIMARY
CAS
149647-78-9
Created by admin on Mon Oct 21 20:47:07 UTC 2019 , Edited by admin on Mon Oct 21 20:47:07 UTC 2019
PRIMARY
MERCK INDEX
M11502
Created by admin on Mon Oct 21 20:47:06 UTC 2019 , Edited by admin on Mon Oct 21 20:47:06 UTC 2019
PRIMARY Merck Index
HSDB
149647-78-9
Created by admin on Mon Oct 21 20:47:06 UTC 2019 , Edited by admin on Mon Oct 21 20:47:06 UTC 2019
PRIMARY
PUBCHEM
5311
Created by admin on Mon Oct 21 20:47:06 UTC 2019 , Edited by admin on Mon Oct 21 20:47:06 UTC 2019
PRIMARY
RXCUI
194337
Created by admin on Mon Oct 21 20:47:06 UTC 2019 , Edited by admin on Mon Oct 21 20:47:06 UTC 2019
PRIMARY RxNorm
MESH
C111237
Created by admin on Mon Oct 21 20:47:07 UTC 2019 , Edited by admin on Mon Oct 21 20:47:07 UTC 2019
PRIMARY
INN
8661
Created by admin on Mon Oct 21 20:47:06 UTC 2019 , Edited by admin on Mon Oct 21 20:47:06 UTC 2019
PRIMARY
NCI_THESAURUS
C1796
Created by admin on Mon Oct 21 20:47:07 UTC 2019 , Edited by admin on Mon Oct 21 20:47:07 UTC 2019
PRIMARY
IUPHAR
6852
Created by admin on Mon Oct 21 20:47:06 UTC 2019 , Edited by admin on Mon Oct 21 20:47:06 UTC 2019
PRIMARY
WIKIPEDIA
VORINOSTAT
Created by admin on Mon Oct 21 20:47:07 UTC 2019 , Edited by admin on Mon Oct 21 20:47:07 UTC 2019
PRIMARY
EPA CompTox
149647-78-9
Created by admin on Mon Oct 21 20:47:06 UTC 2019 , Edited by admin on Mon Oct 21 20:47:06 UTC 2019
PRIMARY
EVMPD
SUB23356
Created by admin on Mon Oct 21 20:47:07 UTC 2019 , Edited by admin on Mon Oct 21 20:47:07 UTC 2019
PRIMARY
DRUG BANK
DB02546
Created by admin on Mon Oct 21 20:47:06 UTC 2019 , Edited by admin on Mon Oct 21 20:47:06 UTC 2019
PRIMARY
Related Record Type Details
TARGET -> INHIBITOR
BINDING
IC50
TARGET -> INHIBITOR
BINDING
IC50
METABOLIC ENZYME -> SUBSTRATE
EXCRETED UNCHANGED
AMOUNT EXCRETED
URINE
TARGET -> INHIBITOR
BINDING
IC50
TARGET -> INHIBITOR
BINDING
IC50
METABOLIC ENZYME -> SUBSTRATE
TARGET -> INHIBITOR
BINDING
IC50
METABOLIC ENZYME -> SUBSTRATE
METABOLIC ENZYME -> SUBSTRATE
METABOLIC ENZYME -> SUBSTRATE
BINDER->LIGAND
BINDING
TARGET ORGANISM->INHIBITOR
METABOLIC ENZYME -> SUBSTRATE
TARGET -> INHIBITOR
BINDING
IC50
METABOLIC ENZYME -> SUBSTRATE
Related Record Type Details
METABOLITE -> PARENT
METABOLITE -> PARENT
METABOLITE -> PARENT
METABOLITE -> PARENT
METABOLITE -> PARENT
METABOLITE INACTIVE -> PARENT
PLASMA
METABOLITE -> PARENT
METABOLITE INACTIVE -> PARENT
MAJOR
URINE
METABOLITE -> PARENT
METABOLITE INACTIVE -> PARENT
URINE
METABOLITE -> PARENT
Related Record Type Details
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