Vorinostat (SAHA, MK0683)

Catalog No.S1047

Vorinostat (suberoylanilide hydroxamic acid, SAHA) is an HDAC inhibitor with IC50 of ~10 nM in a cell-free assay.

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Vorinostat (SAHA, MK0683) Chemical Structure

Vorinostat (SAHA, MK0683) Chemical Structure
Molecular Weight: 264.3

Validation & Quality Control

Cited by 99 publications:

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Related Compound Libraries

HDAC Inhibitors with Unique Features

Product Information

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  • Research Area
  • Vorinostat (SAHA, MK0683) Mechanism
  • Combination Therapy
    Combination Therapy

Product Description

Biological Activity

Description Vorinostat (suberoylanilide hydroxamic acid, SAHA) is an HDAC inhibitor with IC50 of ~10 nM in a cell-free assay.
Targets HDAC [1]
(Cell-free assay)
IC50 ~10 nM
In vitro Vorinostat inhibits the activities of HDAC1 and HDAC3 with IC50 of 10 nM and 20 nM, respectively. Vorinostat also results in a marked hyperacetylation of histone H4. [1] Vorinostat inhibits the growth of three prostate cancer cell lines LNCaP, PC-3 and TSU-Pr1 at micromolar concentrations (2.5-7.5 μM), and induces dose-dependent cell death in LNCaP cells. [2] Vorinostat treatment in MCF-7 cells inhibits cell proliferation at an IC50 of 0.75 μM resulting in the accumulation of cells in the G1 and G2-M phase of the cell cycle. Vorinostat also induces differentiation in the estrogen receptor-negative cell line SKBr-3 and the retinoblastoma-negative cell line MDA-468. [3] Vorinostat treatment at 1 μM for 8 hours or more is sufficient to irreversibly induce apoptosis of human multiple myeloma (MM) cells. The gene expression profiles of Vorinostat treated MM cells are not hallmarked by global transcriptional activation, but by coordinated transcriptional changes of specific functional groups of genes such as cytokine-induced proliferative/survival signaling cascades, oncogenes-tumor suppressor genes, regulators of apoptosis, DNA synthesis-repair and cell cycle, and proteasome-ubiquitin function. [4]
Cell Data
Cell LinesAssay TypeConcentrationIncubation TimeFormulationActivity DescriptionPMID
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D-336MGNXP3N3l5T3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm=NHPCW21KSzVyPUSxMlg1PDJizszNMl3sV2FPT0WU
UACC-62M3Xy[Gdzd3e2aDDJcohq[mm2aX;uJGF{e2G7MkjyTWM2OD12Mj61OVA2KM7:TR?=M{TxOnNCVkeHUh?=
C-33-AMYXHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>?MmHDTWM2OD12NT6zNlU3KM7:TR?=NF\ETFNUSU6JRWK=
HCC1937NVrDNpFET3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm=NUDDRoZ[UUN3ME20O{4yQTV6IN88US=>NFfyZZhUSU6JRWK=
HDLM-2MVLHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>?MkXmTWM2OD12Nz6yNlg4KM7:TR?=NGPwdGpUSU6JRWK=
NCI-H727NITEfXNIem:5dHigTY5pcWKrdHnvckBCe3OjeR?=MUjJR|UxRTR5LkK0OVEh|ryPNXjQUpN7W0GQR1XS
NYMmq4S5Jwf3SqIFnubIljcXSrb36gRZN{[Xl?NX\CfJdmUUN3ME20PU4{QTB6IN88US=>MV3TRW5ITVJ?
NCI-H2291Mm[4S5Jwf3SqIFnubIljcXSrb36gRZN{[Xl?NXruZ5BsUUN3ME20PU45OzBzIN88US=>M1jpZnNCVkeHUh?=

... Click to View More Cell Line Experimental Data

In vivo Administration of Vorinostat (~100 mg/kg/day) significantly inhibits the growth of CWR22 human prostate xenografts in nude mice with tumor reductions of 78%, 97% and 97%, at doses of 25 mg/kg/day, 50 mg/kg/day and 100 mg/kg/day, respectively, compared with control. Vorinostat induces the accumulation of acetylated core histones and prostate-specific antigen mRNA expression in CWR22 cells, resulting in higher levels of serum prostate-specific antigen than predicted from tumor volume alone. [2] Oral administration of Vorinostat (0.67g/L) crosses the blood-brain barrier, increases histone acetylation in the brain, and dramatically improves the motor impairment in the R6/2 mice model of Huntington's disease. [5]
Features

Protocol(Only for Reference)

Kinase Assay:

[1]

Immunoprecipitation-HDAC assays The lysate of Jurkat cells is incubated for 1 hour on ice and cleared by centrifugation at 12,000 g for 10 minutes at 4 °C. Supernatants are precleared with 30 μL of 50% protein G-Sepharose slurry for 1 hour at 4 °C. Beads are pelleted by centrifugation and supernatants are incubated for 1 hour at 4 °C with 10 μg of IgG fraction from anti-HDAC1 or HDAC3 polyclonal antisera (preincubated 2 hours at room temperature with either the homologous or heterologous immunizing peptide). Both antisera are raised in rabbits against the carboxylterminal peptide of HDAC1 and HDAC3 by using synthetic peptides coupled to keyhole limpet hemocyanin. 30 μL of 50% protein G-Sepharose slurry is added for 1 hour at 4 °C. Immune complexes are pelleted by centrifugation and washed three times with 1 mL of lysis buffer. Beads are resuspended in 200 μL of HDAC buffer (20 mM Tris-HCl, pH 8.0/150 mM NaCl/10% glycerol), and the HDAC assay is performed with an 3H-acetylated peptide corresponding to amino acids 1-24 of histone H4. Released [3H]acetic acid is quantified by scintillation counting. For inhibitions studies, the immunoprecipitated complexes are preincubated with the different concentrations of Vorinostat for 30 minutes at 4 °C.

Cell Assay:

[2]

Cell lines LNCaP, PC-3, and TSU-Pr1
Concentrations Dissolved in DMSO, final concentrations ~7.5 μM
Incubation Time 1, 2, 3 and 4 days
Method

Cells are exposed to various concentrations of Vorinostat for 1, 2, 3 and 4 days. Cell viability is assessed by trypan blue dye exclusion.

Animal Study:

[2]

Animal Models Male BALB/c nude (nu/nu) mice implanted with CWR22 tumor cells
Formulation Dissolved in DMSO
Dosages ~100 mg/kg/day
Administration Injection i.p.

Conversion of different model animals based on BSA (Value based on data from FDA Draft Guidelines)

SpeciesMouseRatRabbitGuinea pigHamsterDog
Weight (kg)0.020.151.80.40.0810
Body Surface Area (m2)0.0070.0250.150.050.020.5
Km factor36128520
Animal A (mg/kg) = Animal B (mg/kg) multiplied by  Animal B Km
Animal A Km

For example, to modify the dose of resveratrol used for a mouse (22.4 mg/kg) to a dose based on the BSA for a rat, multiply 22.4 mg/kg by the Km factor for a mouse and then divide by the Km factor for a rat. This calculation results in a rat equivalent dose for resveratrol of 11.2 mg/kg.

Rat dose (mg/kg) = mouse dose (22.4 mg/kg) ×  mouse Km(3)  = 11.2 mg/kg
rat Km(6)
1

References

[1] Richon VM, et al. Proc Natl Acad Sci U S A, 1998, 95(6), 3003-3007.

[2] Butler LM, et al. Cancer Res, 2000, 60(18), 5165-5170.

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Clinical Trial Information( data from http://clinicaltrials.gov, updated on 2016-07-30)

NCT Number Recruitment Conditions Sponsor
/Collaborators
Start Date Phases
NCT02589145 Recruiting Lymphoma M.D. Anderson Cancer Center|Celgene Corporation June 2016 Phase 1|Phase 2
NCT02836548 Recruiting Melanoma|Skin Neoplasms The Netherlands Cancer Institute June 2016 Phase 1|Phase 2
NCT02707900 Not yet recruiting HIV-1 Infection Cynthia L Gay, MD|National Institute of Allergy and Infec  ...more Cynthia L Gay, MD|National Institute of Allergy and Infectious Diseases (NIAID)|University of North Carolina, Chapel Hill March 2016 Phase 1
NCT02638090 Recruiting Lung Cancer|Non-small Cell Lung Cancer H. Lee Moffitt Cancer Center and Research Institute|Merck  ...more H. Lee Moffitt Cancer Center and Research Institute|Merck Sharp & Dohme Corp. February 2016 Phase 1|Phase 2
NCT02619253 Recruiting Renal Cell Carcinoma|Urinary Bladder Neoplasms Roberto Pili|Indiana University January 2016 Phase 1|Phase 2

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Chemical Information

Download Vorinostat (SAHA, MK0683) SDF
Molecular Weight (MW) 264.3
Formula

C14H20N2O3

CAS No. 149647-78-9
Storage 3 years -20℃powder
6 months-80℃in solvent
Synonyms N/A
Solubility (25°C) * In vitro DMSO 53 mg/mL (200.52 mM)
Ethanol 3 mg/mL (11.35 mM)
Water <1 mg/mL (<1 mM)
In vivo 2% DMSO+30% PEG 300+ddH2O 5mg/mL
* <1 mg/ml means slightly soluble or insoluble.
* Please note that Selleck tests the solubility of all compounds in-house, and the actual solubility may differ slightly from published values. This is normal and is due to slight batch-to-batch variations.
Chemical Name N1-​hydroxy-​N8-​phenyl-octanediamide

Frequently Asked Questions

  • Question 1
    What’s the recommendation about reconstitution of the compound for in vivo animal study?

    Answer: We recommend the following vehicle for S1047: 2% DMSO, 40% PEG 300, 5% Propylene glycol, 1% Tween 80 at 5 mg/mL.

Tech Support

Answers to questions you may have can be found in the inhibitor handling instructions. Topics include how to prepare stock solutions, how to store inhibitors, and issues that need special attention for cell-based assays and animal experiments.

Tel: +1-832-582-8158 Ext:3

If you have any other enquiries, please leave a message.

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