Belinostat

製品コードS1085 バッチS108504

印刷

化学情報

Chemical Structure Synonyms PXD101,NSC726630, PX-105684 Storage
(From the date of receipt)		 3 years -20°C powder
1 years -80°C in solvent
化学式

C15H14N2O4S
分子量 318.35 CAS No. 866323-14-0
Solubility (25°C)* 体外 DMSO 63 mg/mL (197.89 mM)
Ethanol 51 mg/mL (160.2 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.
* <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 Belinostat is a novel HDAC inhibitor with IC50 of 27 nM in a cell-free assay, with activity demonstrated in cisplatin-resistant tumors. Belinostat (PXD101) induces autophagy.
in vitro Belinostat inhibits the growth of tumor cells (A2780, HCT116, HT29, WIL, CALU-3, MCF7, PC3 and HS852) with IC50 from 0.2-0.66 μM. PD101 shows low activity in A2780/cp70 and 2780AD cells, which are cisplatin and doxorubicin-resistant derivatives of A2780 cells. This compound could induce apoptosis through PARP cleavage and acetylation of histones H3/H4. [1] It inhibits bladder cancer cell growth, especially in 5637 cells, which shows accumulation of G0-G1 phase, decrease in S phase and increase in G2-M phase. [2] The growth inhibitory activity of this chemical on cell lines is not strongly influenced by the multidrug-resistant phenotype, whereas the activity of docetaxel is clearly affected. It could enhance the growth inhibitory activity of docetaxel or carboplatin in OVCAR-3 and A2780 cells. This compound also shows enhanced tubulin acetylation in ovarian cancer cell lines. [3] A recent study shows that it activates protein kinase A in a TGF-β signaling-dependent mechanism and decreases survivin mRNA. [4]
in vivo Belinostat indicates significant tumor growth delay in A2780 and A2780/cp70 xenograft at a dose of 10mg/kg with no effects on the body weight. [1] This compound also induces p21WAF1, HDAC core and cell communication genes in mouse bladder tumors. [2] Its monotherapy induces dose-proportional antitumor effects with TGI of 47% at a dose of 100mg/kg in A2780 xenograft. The combination of this chemical (100 mg/kg) with carboplatin (40 mg/kg) could delay tumor growth from 18.6 days to 22.5 days. [3] Combining with bortezomib, it results in great tumor inhibition and gastrointestinal toxicity in mice with bortezomib-resistant UMSCC-11A xenograft. [5]
特徴 Lead compound of Topotarget.

プロトコル(参考用のみ)

キナーゼアッセイ Histone Deacetylase Activity
Subconfluent cultures are harvested and washed twice in ice cold PBS and pelleted by centrifugation at 200 × g for 5 min. The cell pellet is resuspended in two volumes of lysis buffer [60 mM Tris buffer (pH 7.4) containing 30% glycerol and 450 mM NaCl] and lysed by three freeze (dry ice) thaw (30 °C water bath) cycles. Cell debris is removed by centrifugation at 1.2 × 104 g for 5 min, and the supernatant is stored at −80 °C. Histone H4 peptide (sequence SGRGKGGKGLGKGGAKRHRK corresponding to the 20 NH2-terminal residues) is acetylated by a recombinant protein containing the hypoxanthine-aminopterin-thymidine domain of p300, using [3H]acetyl CoA as a source of acetate. H4 peptide (100 μg) is mixed with hypoxanthine-aminopterin-thymidine buffer (50 mM Tris HCl pH 8.0, 5% glycerol, 50 mM KCl, and 0.1 mM EDTA), 1 mM DTT, 1 mM 4-(2-aminoethyl) benzenesulfonylfluoride, 1 × complete protease inhibitors, 50 μL of purified p300, and 1.85 m [3H]acetyl CoA (4.50Ci/mmol) in a final volume of 300 μL and incubated at 30 °C for 45 min. The p300 protein is removed by incubation with 20 μL of 50% Ni-agaroase beads for 1 hour at 4 °C and centrifugation. The supernatant is applied to a 2 mL Sephadex G15 column, and the flow through is collected. One milliliter of distilled H2O is gently applied, and three drop fractions are collected; this is repeated until 4–5 mL of distilled H2O has been added, and ∼40 fractions are collected. Three microliters of each fraction are diluted in 2 mL of scintillation fluid and counted in a scintillation counter to identify the fractions containing the labeled peptide. These fractions are pooled, and 1 μL of the combined sample is measured to assess the radioactivity in every peptide batch (3-7×103 cpm/μL). For activity assays, the reaction is carried out in a total volume of 150 μL of buffer [60 mM Tris (pH 7.4) containing 30% glycerol] containing 2 μL of cell extract and, where used, 2 μL of this compound. The reaction is started by the addition of 2 μL of [3H] labeled substrate (acetylated histone H4 peptide corresponding to the 20 NH2-terminal residues). Samples are incubated at 37 °C for 45 min, and the reaction stopped by the addition of HCl and acetic acid (0.72 and 0.12 M final concentrations, respectively). Released [3H]acetate is extracted into 750 μL of ethyl acetate, and samples are centrifuged at 1.2× 104 g for 5 min. The upper phase (600 μL) is transferred to 3 mL of scintillation fluid and counted.
細胞アッセイ 細胞株 A2780, A2780/cp70, 2780AD, HCT116, HT29, WIL, CALU-3, MCF7, PC3 and HS852
濃度 0.016 - 10 μM
反応時間 24 hours
実験の流れ Tumor cell lines are seeded in 5 mL of medium at a density of 8 × 104 cells/25 cm2 flask and incubated for 48 hours. Cells are exposed to Belinostat (0.016 to 10 μM) for 24 hours. The medium is removed, and 1 mL of trypsin/EDTA is added to each flask. Once the cells have detached, 1 mL of medium is added, the cells are resuspended, and those from the control untreated flask are counted. Cells are diluted and plated into 6-cm Petri dishes (three per flask) at a density of 0.5-2× 103 cells/dish depending on the cell line. Cells from the drug-treated flasks are diluted and plated as for the control flasks. Dishes are incubated for 10–15 days at 37 °C. Cells are washed with PBS, fixed in methanol, and stained with crystal violet, and colonies that contained ≥50 cells counted. Sensitivity is expressed as the IC50 defined as the concentration of this compound required to reduce the number of colonies to 50% of that of the control untreated cells.
動物実験 動物モデル A2780, A2780/cp70 and HCT116 cells are injected s.c. into the right flank of CD1 nu/nu mice.
投薬量 ≤40 mg/kg
投与方法 Administered via i.p.

参考

  • https://pubmed.ncbi.nlm.nih.gov/12939461/
  • https://pubmed.ncbi.nlm.nih.gov/17935615/
  • https://pubmed.ncbi.nlm.nih.gov/16928830/
  • https://pubmed.ncbi.nlm.nih.gov/21757750/
  • https://pubmed.ncbi.nlm.nih.gov/17237265/

カスタマーフィードバック

Data from [Breast Cancer Res Treat , 2012, 131, 777-789]

Data from [PLoS One, 2011, 6, e17138]

Data from [PLoS One, 2011, 6, e17138]

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：

A patient-derived T cell lymphoma biorepository uncovers pathogenetic mechanisms and host-related therapeutic vulnerabilities [ Cell Rep Med, 2025, S2666-3791(25)00102-8] PubMed: 40147445
Deacetylation of TALDO1 by HDAC6 promotes glycolysis and nasopharyngeal carcinoma progression through a moonlighting function [ Cell Death Dis, 2025, 16(1):743] PubMed: 41120289
The anticancer effect of the HDAC inhibitor belinostat is enhanced by inhibitors of Bcl-xL or Mcl-1 in ovarian cancer [ Mol Oncol, 2025, 10.1002/1878-0261.70050] PubMed: 40483575
The anticancer effect of the HDAC inhibitor belinostat is enhanced by inhibitors of Bcl-xL or Mcl-1 in ovarian cancer [ Mol Oncol, 2025, 10.1002/1878-0261.70050] PubMed: 40483575
Targeting the akt/mtor signaling pathway by maprotiline leads to tumor suppression in T-cell lymphoma [ Ann Hematol, 2025, 10.1007/s00277-025-06571-z] PubMed: 40892074
Role of the NuRD complex and altered proteostasis in cancer cell quiescence [ bioRxiv, 2025, 2025.02.10.637435] PubMed: 39990343
Orthogonal proteogenomic analysis identifies the druggable PA2G4-MYC axis in 3q26 AML [ Nat Commun, 2024, 15(1):4739] PubMed: 38834613
Interferon-induced factor 16 is essential in metastatic melanoma to maintain STING levels and the immune responses upon IFN-γ response pathway activation [ J Immunother Cancer, 2024, 12(10)e009590] PubMed: 39424359
Chronic hypoxia stabilizes 3βHSD1 via autophagy suppression [ Cell Rep, 2024, 43(1):113575] PubMed: 38181788
PXD101 inhibits malignant progression and radioresistance of glioblastoma by upregulating GADD45A [ J Transl Med, 2024, 22(1):1047] PubMed: 39568000

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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