Belinostat (PXD101)
(Synonyms: 贝利司他(PXD101),PXD-101, PXD 101, PX105684, PX-105684) 目录号 : GC15962
Belinostat (PXD101) 是 HeLa 细胞提取物中组蛋白脱乙酰酶 (HDAC) 活性的新型异羟肟酸型抑制剂，IC50 为 27 nM 。
Cas No.:414864-00-9
Sample solution is provided at 25 µL, 10mM.
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Quality Control & SDS
- View current batch:
- Purity: >98.00%
- COA (Certificate Of Analysis)
- SDS (Safety Data Sheet)
- Datasheet
| Kinase experiment [1]: | |
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Preparation Method |
Reaction was 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 Belinostat. The reaction was started by the addition of 2 μl of [3H] labeled substrate (acetylated histone H4 peptide corresponding to the 20 NH2-terminal residues). Samples were 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). |
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Reaction Conditions |
2 μl of Belinostat, incubated at 37°C for 45 min |
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Applications |
Belinostat inhibited histone deacetylase activity in cell lysates with an IC50 in the range 9–100 nM |
| Cell experiment [1]: | |
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Cell lines |
The human ovarian cell line A2780, cisplatin (A2780/cp70) and doxorubicin (2780AD) resistant derivatives |
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Preparation Method |
Cells were plated in 5 ml of medium at a density of 8 × 104 cells/25 cm2 flask and allowed to attach and grow for 48 h. Cells were exposed to Belinostat (five concentrations from 0.016 to 10 μm) for 24 h. |
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Reaction Conditions |
0.016 to 10 μm, for 24 h |
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Applications |
Belinostat inhibited the growth of a number of human tumor cell lines with IC50s determined by a clonogenic assay in the range 0.2–3.4 μm |
| Animal experiment [2]: | |
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Animal models |
female CD-1 athymic nude mice |
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Preparation Method |
Once tumors became established (∼100 mm3 in size), animals were randomized (10 animals/group) and drug treatments were initiated. Belinostat was given by i.p. injection once daily for 15 consecutive days. Belinostat was prepared as a 50 mg/mL stock in Belinostat vehicle (pH ∼9.4) and for administration was diluted in Belinostat vehicle to 10 mg/mL (for 100 mg/kg dose) |
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Dosage form |
i.p , 20, 40, 100 mg/kg, for 15 d. |
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Applications |
Belinostat monotherapy induced dose-proportional antitumor effects. When administered at 100 mg/kg, Belinostat inhibited tumor size by 47% at day 15 relative to vehicle-treated control animals. |
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References: [1]. Plumb J A, Finn P W, Williams R J, et al. Pharmacodynamic response and inhibition of growth of human tumor xenografts by the novel histone deacetylase inhibitor PXD101[J]. Molecular cancer therapeutics, 2003, 2(8): 721-728. [2]. Qian X, LaRochelle W J, Ara G, et al. Activity of PXD101, a histone deacetylase inhibitor, in preclinical ovarian cancer studies[J]. Molecular cancer therapeutics, 2006, 5(8): 2086-2095. |
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Belinostat (PXD101) is a novel hydroxamate-type inhibitor of histone deacetylase (HDAC) activity in HeLa cell extracts with an IC50 of 27 nM [1].
Belinostat(1-5 μM)for 48 h caused a dose-dependent inhibition of proliferation, with the most potent inhibitory effect occurring on 5637 cells (IC50 of 1.0 μM), and the least effect occurring on RT4 cells (IC50 of 10.0 μM). T24 and J82 cell lines had an IC50 of 3.5 and 6.0 μM, respectively [2]. Belinostat inhibited the proliferation of human bladder cancer T24 cells with IC50 of 3.5μM [3].
Belinostat (10-40 mg/kg/day i.p.) daily for 7 days causes a significant dose-dependent growth delay with no obvious signs of toxicity to the colon tumor xenografts mice [1]. Gene expression analysis of belinostat-treated mice showed increased p21WAF1 gene transcript expression [3]. Belinostat monotherapy induced dose-proportional antitumor effects. When administered at 100 mg/kg, belinostat inhibited tumor size by 47% at day 15 on human ovarian cancer xenografts [4].
References:
[1]. Plumb J A, Finn P W, Williams R J, et al. Pharmacodynamic response and inhibition of growth of human tumor xenografts by the novel histone deacetylase inhibitor PXD101[J]. Molecular cancer therapeutics, 2003, 2(8): 721-728.
[2]. Buckley M T, Yoon J, Yee H, et al. The histone deacetylase inhibitor belinostat (PXD101) suppresses bladder cancer cell growth in vitro and in vivo[J]. Journal of Translational Medicine, 2007, 5(1): 1-12.
[3]. Buckley M T, Yoon J, Yee H, et al. The histone deacetylase inhibitor belinostat (PXD101) suppresses bladder cancer cell growth in vitro and in vivo[J]. Journal of Translational Medicine, 2007, 5(1): 1-12.
[4]. Qian X, LaRochelle W J, Ara G, et al. Activity of PXD101, a histone deacetylase inhibitor, in preclinical ovarian cancer studies[J]. Molecular cancer therapeutics, 2006, 5(8): 2086-2095.
Belinostat (PXD101) 是 HeLa 细胞提取物中组蛋白脱乙酰酶 (HDAC) 活性的新型异羟肟酸型抑制剂，IC50 为 27 nM [1]。
Belinostat(1-5 μM) 48 h 引起剂量依赖性增殖抑制，对 5637 细胞的抑制作用最强（IC50 为 1.0 μM），对 RT4 细胞的作用最小（IC50 为10.0 μM）。 T24 和 J82 细胞系的 IC50 分别为 3.5 和 6.0 μM [2]。 Belinostat抑制人膀胱癌T24细胞增殖，IC50为3.5μM [3]。
Belinostat（10-40 mg/kg/天 i.p.）每天持续 7 天会导致显着的剂量依赖性生长延迟，而对结肠肿瘤异种移植小鼠没有明显的毒性迹象[1]。 belinostat 治疗小鼠的基因表达分析显示 p21WAF1 基因转录物表达增加[3]。 Belinostat 单一疗法诱导剂量成比例的抗肿瘤作用。当以 100 mg/kg 的剂量给药时，belinostat 在第 15 天时抑制了人卵巢癌异种移植物肿瘤大小的 47% [4]。
| Cas No. | 414864-00-9 | SDF | |
| 别名 | 贝利司他(PXD101),PXD-101, PXD 101, PX105684, PX-105684 | ||
| 化学名 | (E)-N-hydroxy-3-[3-(phenylsulfamoyl)phenyl]prop-2-enamide | ||
| Canonical SMILES | C1=CC=C(C=C1)NS(=O)(=O)C2=CC=CC(=C2)C=CC(=O)NO | ||
| 分子式 | C15H14N2O4S | 分子量 | 318.35 |
| 溶解度 | ≥ 15.92 mg/mL in DMSO, ≥ 44.1 mg/mL in EtOH with ultrasonic | 储存条件 | Store at -20°C |
| General tips | 请根据产品在不同溶剂中的溶解度选择合适的溶剂配制储备液；一旦配成溶液，请分装保存，避免反复冻融造成的产品失效。 储备液的保存方式和期限：-80°C 储存时，请在 6 个月内使用，-20°C 储存时，请在 1 个月内使用。 为了提高溶解度，请将管子加热至37℃，然后在超声波浴中震荡一段时间。 |
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| Shipping Condition | 评估样品解决方案：配备蓝冰进行发货。所有其他可用尺寸：配备RT，或根据请求配备蓝冰。 | ||
| 制备储备液 | |||
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1 mg | 5 mg | 10 mg |
| 1 mM | 3.1412 mL | 15.706 mL | 31.412 mL |
| 5 mM | 0.6282 mL | 3.1412 mL | 6.2824 mL |
| 10 mM | 0.3141 mL | 1.5706 mL | 3.1412 mL |
| 第一步：请输入基本实验信息（考虑到实验过程中的损耗，建议多配一只动物的药量） | ||||||||||
| 给药剂量 | mg/kg |  |
动物平均体重 | g | |
每只动物给药体积 | ul | |
动物数量 | 只 |
| 第二步：请输入动物体内配方组成（配方适用于不溶于水的药物；不同批次药物配方比例不同，请联系GLPBIO为您提供正确的澄清溶液配方） | ||||||||||
| % DMSO % % Tween 80 % saline | ||||||||||
| 计算重置 | ||||||||||
计算结果:
工作液浓度： mg/ml；
DMSO母液配制方法： mg 药物溶于 μL DMSO溶液（母液浓度 mg/mL，
体内配方配制方法：取 μL DMSO母液，加入 μL PEG300，混匀澄清后加入μL Tween 80，混匀澄清后加入 μL saline，混匀澄清。
1. 首先保证母液是澄清的；
2.
一定要按照顺序依次将溶剂加入，进行下一步操作之前必须保证上一步操作得到的是澄清的溶液，可采用涡旋、超声或水浴加热等物理方法助溶。
3. 以上所有助溶剂都可在 GlpBio 网站选购。
Belinostat (PXD101) resists UVB irradiation-induced cellular senescence and skin photoaging
Biochem Biophys Res Commun2022 Oct 30;627:122-129.PMID: 36030653DOI: 10.1016/j.bbrc.2022.08.038
Belinostat (PXD101), a new histone deacetylase inhibitor, has shown good performance in various cancer treatments and has been approved by the FDA for the treatment of recurrent or refractory peripheral T-cell lymphoma (PTCL) in patients with drugs. PXD101 is considered to have certain anti-allergic and anti-inflammatory properties, but its beneficial effects in UVB-induced skin photoaging have not been reported. In a recent study, HacaT cells and C57BL6 mice were used to study the impact of PXD101 on UVB-induced cellular senescence and skin photoaging and to explore their potential mechanisms of action. Studies have shown that PXD101 inhibits UVB-induced HacaT cell senescence, which appears to be achieved by inhibiting activation of the UVB-induced NF-κB/p65 signaling pathway. At the same time, PXD101 inhibits the expression of MMPs. In addition, PXD101 alleviated skin damage on the dorsal skin of mice, reduced skin aging and inflammation, increased collagen fiber synthesis, and restored UVB-induced epidermal thickening. In short, we believe that PXD101 effectively inhibits cellular senescence and skin photoaging caused by UVB exposure, a potential method for developing clinical prevention and treatment of skin aging.