Vorinostat (SAHA)

製品コードS1047 バッチS104716

印刷

化学情報

Chemical Structure Synonyms MK0683, Suberoylanilide hydroxamic acid Storage
(From the date of receipt)		 3 years -20°C powder
1 years -80°C in solvent
化学式

C14H20N2O3
分子量 264.3 CAS No. 149647-78-9
Solubility (25°C)* 体外 DMSO 53 mg/mL (200.52 mM)
Ethanol 18 mg/mL (68.1 mM)
Water Insoluble
体内 （毎回新しく調製した物を用意してください）
Homogeneous suspension
CMC-NA
≥5mg/ml Taking the 1 mL working solution as an example, add 5 mg of this product to 1 ml of CMC-Na solution, mix evenly to obtain a homogeneous suspension with a final concentration of 5 mg/ml.
Clear solution
5%DMSO Corn oil

この製剤はselleckのラボで検証済みです。上記の溶解方法がご要望を満たさない場合、selleckの営業担当までお問い合わせ頂ければ、個別の試験を行います。

 2.500mg/ml (9.46mM) Taking the 1 mL working solution as an example, add 50 μL of 50 mg/ml clear DMSO stock solution to 950 μL of corn oil and mix evenly. The mixed solution should be used immediately for optimal results. 
* <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.

溶剤液（一定の濃度）を調合する

生物活性

製品説明 Vorinostat (SAHA) is an HDAC inhibitor with IC50 of ~10 nM in a cell-free assay. Vorinostat abrogates productive HPV-18 DNA amplification.
in vitro

Vorinostat (SAHA) inhibits the activities of HDAC1 and HDAC3 with IC50 of 10 nM and 20 nM, respectively, and also results in a marked hyperacetylation of histone H4. [1] This compound 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] Its 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. It also induces differentiation in the estrogen receptor-negative cell line SKBr-3 and the retinoblastoma-negative cell line MDA-468. [3] Treatment with this compound 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 (SAHA) (~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. This compound 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 it (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]

プロトコル(参考用のみ)

キナーゼアッセイ 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 (SAHA) for 30 minutes at 4 °C.
細胞アッセイ 細胞株 LNCaP, PC-3, and TSU-Pr1
濃度 Dissolved in DMSO, final concentrations ~7.5 μM
反応時間 1, 2, 3 and 4 days
実験の流れ

Cells are exposed to various concentrations of Vorinostat (SAHA) for 1, 2, 3 and 4 days, and cell viability is assessed by trypan blue dye exclusion.
動物実験 動物モデル Male BALB/c nude (nu/nu) mice implanted with CWR22 tumor cells
投薬量 25, 50, and 100 mg/kg/day
投与方法 Injection i.p.

参考

  • https://pubmed.ncbi.nlm.nih.gov/9501205/
  • https://pubmed.ncbi.nlm.nih.gov/11016644/
  • https://pubmed.ncbi.nlm.nih.gov/11731433/
  • https://pubmed.ncbi.nlm.nih.gov/12576549/
  • https://pubmed.ncbi.nlm.nih.gov/14695887/
  • https://pubmed.ncbi.nlm.nih.gov/15173093/
  • https://pubmed.ncbi.nlm.nih.gov/18765530/
  • https://pubmed.ncbi.nlm.nih.gov/18505786/

カスタマーフィードバック

Data from [J Exp Med, 2012, 209, 35-50]

Data from [Clin Cancer Res, 2012, 18, 3822-33]

Data from [Diabetologia, 2012, 55, 2421-2431]

Selleckの高級品が、幾つかの出版された研究調査結果（以下を含む）で使われた：

Co-targeting of epigenetic regulators and BCL-XL improves efficacy of immune checkpoint blockade therapy in multiple solid tumors [ Mol Cancer, 2025, 24(1):154] PubMed: 40442785
Intratumor heterogeneity of EGFR expression mediates targeted therapy resistance and formation of drug tolerant microenvironment [ Nat Commun, 2025, 16(1):28] PubMed: 39747003
Dual targeting of CDK6 and LSD1 is synergistic and overcomes differentiation blockade in AML [ EMBO Mol Med, 2025, 10.1038/s44321-025-00296-2] PubMed: 40883610
Heterozygous Kmt2d loss diminishes enhancers to render medulloblastoma cells vulnerable to combinatory inhibition of LSD1 and OXPHOS [ Cell Rep, 2025, 44(5):115619] PubMed: 40286267
A STAT3/integrin axis accelerates pancreatic cancer initiation and progression [ Cell Rep, 2025, S2211-1247(25)00781-8] PubMed: 40701148
DNMT inhibition epigenetically restores the cGAS-STING pathway and activates RIG-I/MDA5-MAVS to enhance antitumor immunity [ Acta Pharmacol Sin, 2025, 10.1038/s41401-025-01639-y] PubMed: 40830678
Integrator complex subunit 12 knockout overcomes a transcriptional block to HIV latency reversal [ Elife, 2025, 13RP103064] PubMed: 40207620
The integrative genomic and functional immunological analyses of colorectal cancer initiating cells to modulate stemness properties and the susceptibility to immune responses [ J Transl Med, 2025, 23(1):193] PubMed: 39962504
Targeting hypoxia-inducible factor-1 in a hypoxidative stress model protects retinal pigment epithelium cells from cell death and metabolic dysregulation [ Cell Death Discov, 2025, 11(1):380] PubMed: 40813365
Inhibition of the Integrated stress response by Epstein-Barr virus oncoprotein LMP1 attenuates epithelial cell differentiation and lytic viral reactivation [ PLoS Pathog, 2025, 21(2):e1012934] PubMed: 39951426

長期の保管のために-20°Cの下で製品を保ってください。

人間や獣医の診断であるか治療的な使用のためにでない。

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