Antibodies
Vorinostat (SAHA, MK0683)
- 貨號 Cat. No.
- S1047
- 規格 Size
- 10mM/1mLã€200mgã€500mg
- 品牌 Brand
- Selleckchem
Description
Vorinostat (SAHA, MK0683)
Vorinostat (suberoylanilide hydroxamic acid, SAHA) is an HDAC inhibitor with IC50 of ~10 nM.
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Distributor Tel: +886-2-2827-1197jimmy@new.abscience.com.tw
Biological Activity
| Description | Vorinostat (suberoylanilide hydroxamic acid, SAHA) is an HDAC inhibitor with IC50 of ~10 nM. | |||||
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| Targets | HDAC | |||||
| IC50 | ~10 nM [1] | |||||
| 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] | |||||
| 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:
| 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. |
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Cell Assay:
| Cell lines | LNCaP, PC-3, and TSU-Pr1 |
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| 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:
| Animal Models | Male BALB/c nude (nu/nu) mice implanted with CWR22 tumor cells |
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| Dosages | ~100 mg/kg/day |
| Administration | Injection i.p. |
| Solubility | 30% PEG400/0.5% Tween80/5% propylene glycol 5 mg/mL |
References
Clinical Trial Information( data from http://clinicaltrials.gov)
| NCT Number | Recruitment | Conditions | Sponsor /Collaborators | Start Date | Phases |
|---|---|---|---|---|---|
| NCT01501370 | Withdrawn | Multiple Myeloma | University of Turin, Italy|Tiziana Marangon | 2013-01 | Phase 2 |
| NCT00858234 | Completed | Multiple Myeloma | Merck Sharp & Dohme Corp. | 2013-03 | Phase 1 |
| NCT01319383 | Recruiting | HIV-1 Infection | University of North Carolina, Chapel Hill|National Institutes of Health (NIH)|Merck Sharp & Dohme Corp.|National Institute of Allergy and Infectious Diseases (NIAID) | 2013-03 | Phase 1|Phase 2 |
| NCT00128102 | Completed | Mesothelioma|Lung Cancer | Merck Sharp & Dohme Corp. | 2013-06 | Phase 3 |
| NCT01394354 | Recruiting | Multiple Myeloma in Relapse | University Hospital Freiburg|Merck Sharp & Dohme Corp.|Janssen-Cilag Ltd. | 2013-08 | Phase 1|Phase 2 |
| NCT01617226 | Recruiting | Leukemia, Myeloid, Acute | University of Birmingham|Leukemia Research Fund|Celgene Corporation|Merck Sharp & Dohme Corp. | 2013-09 | Phase 2 |
Chemical Information
Download Vorinostat (SAHA, MK0683) SDF
| Molecular Weight (MW) | 264.3 |
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| Formula | C14H20N2O3 |
| CAS No. | 149647-78-9 |
| Storage | 3 years -20℃Powder |
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| 6 months-80℃in DMSO | |
| Syonnyms | Zolinza, MK-0683 |
| Solubility (25°C) * | In vitro | DMSO | 53 mg/mL (200 mM) |
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| Water | <1 mg/mL (<1 mM) | ||
| Ethanol | 3 mg/mL (11 mM) | ||
| In vivo | 30% PEG400/0.5% Tween80/5% propylene glycol | 5 mg/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. | |||
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Customer Reviews (18)
 Click to enlarge | Rating | |
| Source | Exp Dermatol 2010 19, 1096-1102. Vorinostat (SAHA, MK0683) purchased from Selleck | |
| Method | Tumor volume measurement | |
| Cell Lines | MyLa2059 cells | |
| Concentrations | 60 mg/kg | |
| Incubation Time | ||
| Results | The tumor growth was suppressed in mice treated with vorinostat when compared to mice treated with vehicle. |
Product Citations (53)
CREBBP mutations in relapsed acute lymphoblastic leukaemia. [Mullighan CG, et al. Nature 2011;471(7337):235-9]
Chemoproteomics profiling of HDAC inhibitors reveals selective targeting of HDAC complexes. [Bantscheff M, et al. Nat Biotechnol 2011;29(3):255-65]
A novel murine model of myeloproliferative disorders generated by overexpression of the transcription factor NF-E2. [Kaufmann KB, et al. J Exp Med 2012;209(1):35-50]
