N-hydroxy-N'-phenyloctanediamide

• ChemBase ID: 2276
• Molecular Formular: C14H20N2O3
• Molecular Mass: 264.3202
• Monoisotopic Mass: 264.14739251
• SMILES: O=C(Nc1ccccc1)CCCCCCC(=O)NO
• Canonical SMILES: ONC(=O)CCCCCCC(=O)Nc1ccccc1
• InChI: 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)
• InChIKey: WAEXFXRVDQXREF-UHFFFAOYSA-N

NAMES AND DATABASE IDS

Names

• IUPAC name: N-hydroxy-N'-phenyloctanediamide
• IUPAC Traditional name: SAHA; vorinostat
• Brand Name: Zolinza; SAHA
• Synonyms: N-hydroxy-N′-phenyl-octanediamide; SAHA; Zolinza; MK-0683; N-hydroxy-N'-phenyloctanediamide; suberoylanilide hydroxamic acid; SAHA; N-hydroxy-n'-phenyloctanediamide; N-hyrdroxy-n'-phenyloctanediamide; SHH; Suberanilohydroxamic acid; vorinostat; MK0683; Vorinostat; N-Hydroxy-N’-phenyloctanediamide; Suberoylanilide Hydroxamic Acid

Database IDs

• CAS Number: 149647-78-9
• MDL Number: MFCD00945317
• PubChem SID: 160965729; 46508989
• PubChem CID: 5311

CALCULATED PROPERTIES

JChem

• Acid pKa: 8.907536
• H Acceptors: 3
• H Donor: 3
• LogD (pH = 5.5): 2.0038002
• LogD (pH = 7.4): 1.9907405
• Log P: 2.0039692
• Molar Refractivity: 73.8051 cm^3
• Polarizability: 28.097237 Å^3
• Polar Surface Area: 78.43 Å^2
• Rotatable Bonds: 8
• Lipinski's Rule of Five: true

ALOGPS 2.1

• Log P: 1.88
• LOG S: -3.57
• Solubility (Water): 7.16e-02 g/l

PROPERTIES

Physical Property

• Solubility: DMSO; DMSO: ≥15 mg/mL; Methanol
• Apperance: White Solid; white to tan powder
• Melting Point: 161-162°C
• Hydrophobicity(logP): 0.989

Safety Information

• Storage Condition: -20°C; -20°C Freezer
• European Hazard Symbols: Toxic (T)
• German water hazard class: 3
• Risk Statements: 61-68
• Safety Statements: 53-36/37-45
• GHS Pictograms: GHS08
• GHS Signal Word: Danger
• GHS Hazard statements: H341-H360
• GHS Precautionary statements: P201-P281-P308 + P313
• Storage Temperature: -20°C

Pharmacology Properties

• Target: HDAC

Product Information

• Purity: ≥98% (HPLC); 95%
• Salt Data: Free Base
• Shipped in: wet ice
• Empirical Formula (Hill Notation): C14H20N2O3

DETAILS

DrugBank - DB02546

• Drug Groups: approved; investigational
• Description: Vorinostat (rINN) or suberoylanilide hydroxamic acid (SAHA), is a drug currently under investigation for the treatment of cutaneous T cell lymphoma (CTCL), a type of skin cancer, to be used when the disease persists, gets worse, or comes back during or after treatment with other medicines. It is the first in a new class of agents known as histone deacetylase inhibitors. A recent study suggested that vorinostat also possesses some activity against recurrent glioblastoma multiforme, resulting in a median overall survival of 5.7 months (compared to 4 - 4.4 months in earlier studies). Further brain tumor trials are planned in which vorinostat will be combined with other drugs. [Wikipedia]
• Indication: 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.
• Affected Organisms: Humans and other mammals
• Biotransformation: The major pathways of vorinostat metabolism involve glucuronidation and hydrolysis followed by β-oxidation. Human serum levels of two metabolites, O-glucuronide of vorinostat and 4-anilino-4-oxobutanoic acid were measured. Both metabolites are pharmacologically inactive. Compared to vorinostat, the mean steady state serum exposures in humans of the O-glucuronide of vorinostat and 4-anilino-4-oxobutanoic acid were 4-fold and 13-fold higher, respectively. In vitro studies using human liver microsomes indicate negligible biotransformation by cytochromes P450 (CYP).
• Half Life: 2 hours
• Protein Binding: 71%
• Elimination: In vitro studies using human liver microsomes indicate negligible biotransformation by cytochromes P450 (CYP). Vorinostat is eliminated predominantly through metabolism with less than 1% of the dose recovered as unchanged drug in urine, indicating that renal excretion does not play a role in the elimination of vorinostat. However, renal excretion does not play a role in the elimination of vorinostat.
• References: Munshi A, Tanaka T, Hobbs ML, Tucker SL, Richon VM, Meyn RE: Vorinostat, a histone deacetylase inhibitor, enhances the response of human tumor cells to ionizing radiation through prolongation of gamma-H2AX foci. Mol Cancer Ther. 2006 Aug;5(8):1967-74. [Pubmed]
• External Links: Wikipedia; RxList; Drugs.com

Selleck Chemicals - S1047

Research Area

• Description: Myelodysplastic syndromes, Mesothelioma,Cancer

Protocol

• Protocol: 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.
• Protocol: 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
• Methods:

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

• Protocol: Animal Study ^[2]
• Animal Models: Male BALB/c nude (nu/nu) mice implanted with CWR22 tumor cells
• Formulation: Dissolved in DMSO
• Doses: ~100 mg/kg/day
• Administration: Injection i.p.

References

• References: [1] Richon VM, et al. Proc Natl Acad Sci U S A, 1998, 95(6), 3003-3007.
• References: [2] Butler LM, et al. Cancer Res, 2000, 60(18), 5165-5170.
• References: [3] Munster PN, et al. Cancer Res, 2001, 61(23), 8492-8497.
• References: [4] Hockly E, et al. Natl Acad Sci U S A, 2003, 100(4), 2041-2046.
• References: [5] Mitsiades CS, et al. Proc Natl Acad Sci U S A, 2004, 101(2), 540-545.

Sigma Aldrich - SML0061

Frequently Asked Questions
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Biochem/physiol Actions
Vorinostat or suberoylanilide hydroxamic acid (SAHA) is a potent, reversible pan-histone deacetylase (HDAC) inhibitor. It inhibits both class I and class II HDACs, altering gene transcription and inducing cell cycle arrest and/or apoptosis in a wide variety of transformed cells.

Toronto Research Chemicals - S688700

Suberoylanilide Hydroxamic Acid is a potent, selective, cell permeable histone deacetylase inhibitor (HDAC). Suberoylanilide Hydroxamic Acid displays anti-angiogenic activity by interfering with VEGF signaling in human umbilical vein endothelial cells (H

REFERENCES

• Munshi A, Tanaka T, Hobbs ML, Tucker SL, Richon VM, Meyn RE: Vorinostat, a histone deacetylase inhibitor, enhances the response of human tumor cells to ionizing radiation through prolongation of gamma-H2AX foci. Mol Cancer Ther. 2006 Aug;5(8):1967-74. Pubmed
• Mitsiades CS, et al. Proc Natl Acad Sci U S A, 2004, 101(2), 540-545.
• Richon VM, et al. Proc Natl Acad Sci U S A, 1998, 95(6), 3003-3007.
• Butler LM, et al. Cancer Res, 2000, 60(18), 5165-5170.
• Munster PN, et al. Cancer Res, 2001, 61(23), 8492-8497.
• Hockly E, et al. Natl Acad Sci U S A, 2003, 100(4), 2041-2046.
• Richon, V.M., et al.: Proc. Natl. Acad.Sci. USA, 95, 3003 (1988)
• Munster, P.N., et al.: Cancer Res., 61, 8492 (1988)
• Deroanne, C.F., et al.: Oncogene, 21, 247 (1988)