Pivanex(Synonyms: AN-9; Pivalyloxymethyl butyrate)

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Pivanex (Synonyms: AN-9; Pivalyloxymethyl butyrate)

Pivanex (AN-9) 是丁酸的衍生物,是口服有效的 HDAC 抑制剂。Pivanex 可下调 bcr-abl 蛋白,增强凋亡 (apoptosis)。Pivanex 具有抗转移和抗血管生成的活性

Pivanex(Synonyms: AN-9;  Pivalyloxymethyl butyrate)

Pivanex Chemical Structure

CAS No. : 122110-53-6

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生物活性

Pivanex (AN-9), a derivative of Butyric acid, is an orally active HDAC inhibitor. Pivanex down-regulates bcr-abl protein and enhances apoptosis. Pivanex has antimetastic and antiangiogenic properties[1].

IC50 & Target

HDAC

 

Bcr-Abl

 

体外研究
(In Vitro)

Pivanex (100-500 μM) exhibits significant anti-proliferation activity in K562 cells[1].
Pivanex (100-500 μM) also enhances apoptosis and caspase activity in K562 cells[1].
Pivanex (200 μM) induces enhancement in the G2-M phase, a moderate enhancement in the S phase and a slight reduction in G0-G1 of the cell cycle[1].
Pivanex (AN-9) has selective toxicity to acute leukemia and drug-resistant primary leukemia and cancer cell lines[2].

Shanghai Jinpan Biotech Co Ltd has not independently confirmed the accuracy of these methods. They are for reference only.

Cell Viability Assay[1]

Cell Line: K562 cells.
Concentration: 100-500 μM.
Incubation Time: 24 hours.
Result: Reduced the number of K562 viable cells significantly.
100 μM Pivanex with 0.125 or 0.25 μM STI571 reduced the number of viable cells synergistically.

Apoptosis Analysis[1]

Cell Line: K562 cells.
Concentration: 100-500 μM.
Incubation Time: 6-72 hours.
Result: Increased the number of K562 apoptotic cells significantly.
Increased the caspase activity in K562 cells significantly after only 4 h of incubation with 500 μM.

体内研究
(In Vivo)

Pivanex (AN9, 200 mg/kg, b.i.d, daily) significantly improves the survival of SMN7 SMA mice. Pivanex (AN9) treatment also marked delays the end stage of disease as defined by the onset of body mass loss[3].

Shanghai Jinpan Biotech Co Ltd has not independently confirmed the accuracy of these methods. They are for reference only.

Animal Model: SMN7 SMA mice (SMN2+/+; SMN7+/+; mSmn−/−)[3].
Dosage: 200 mg/kg.
Administration: Oral administration, b.i.d, at 09.00 and 17.00 daily.
Result: Improved the mean lifespan of treated SMN7 SMA mice by 84.6%.
Delayed the onset of body mass loss in SMN7 SMA mice by 94.9%.

Clinical Trial

分子量

202.25

Formula

C10H18O4

CAS 号

122110-53-6

运输条件

Room temperature in continental US; may vary elsewhere.

储存方式

Please store the product under the recommended conditions in the Certificate of Analysis.

溶解性数据
In Vitro: 

DMSO : ≥ 100 mg/mL (494.44 mM)

* “≥” means soluble, but saturation unknown.

配制储备液
浓度 溶剂体积 质量 1 mg 5 mg 10 mg
1 mM 4.9444 mL 24.7219 mL 49.4438 mL
5 mM 0.9889 mL 4.9444 mL 9.8888 mL
10 mM 0.4944 mL 2.4722 mL 4.9444 mL

In Vivo:

请根据您的实验动物和给药方式选择适当的溶解方案。以下溶解方案都请先按照 In Vitro 方式配制澄清的储备液,再依次添加助溶剂:

——为保证实验结果的可靠性,澄清的储备液可以根据储存条件,适当保存;体内实验的工作液,建议您现用现配,当天使用; 以下溶剂前显示的百
分比是指该溶剂在您配制终溶液中的体积占比;如在配制过程中出现沉淀、析出现象,可以通过加热和/或超声的方式助溶

  • 1.

    请依序添加每种溶剂: 10% DMSO    40% PEG300    5% Tween-80    45% saline

    Solubility: ≥ 2.5 mg/mL (12.36 mM); Clear solution

    此方案可获得 ≥ 2.5 mg/mL (12.36 mM,饱和度未知) 的澄清溶液。

    以 1 mL 工作液为例,取 100 μL 25.0 mg/mL 的澄清 DMSO 储备液加到 400 μL PEG300 中,混合均匀;向上述体系中加入50 μL Tween-80,混合均匀;然后继续加入 450 μL生理盐水定容至 1 mL。

    将 0.9 g 氯化钠,完全溶解于 100 mL ddH₂O 中,得到澄清透明的生理盐水溶液

  • 2.

    请依序添加每种溶剂: 10% DMSO    90% (20% SBE-β-CD in saline)

    Solubility: ≥ 2.5 mg/mL (12.36 mM); Clear solution

    此方案可获得 ≥ 2.5 mg/mL (12.36 mM,饱和度未知) 的澄清溶液。

    以 1 mL 工作液为例,取 100 μL 25.0 mg/mL 的澄清 DMSO 储备液加到 900 μL 20% 的 SBE-β-CD 生理盐水水溶液中,混合均匀。

    将 2 g 磺丁基醚 β-环糊精加入 5 mL 生理盐水中,再用生理盐水定容至 10 mL,完全溶解,澄清透明
  • 3.

    请依序添加每种溶剂: 10% DMSO    90% corn oil

    Solubility: ≥ 2.5 mg/mL (12.36 mM); Clear solution

    此方案可获得 ≥ 2.5 mg/mL (12.36 mM,饱和度未知) 的澄清溶液,此方案不适用于实验周期在半个月以上的实验。

    以 1 mL 工作液为例,取 100 μL 25.0 mg/mL 的澄清 DMSO 储备液加到 900 μL玉米油中,混合均匀。

*以上所有助溶剂都可在 Shanghai Jinpan Biotech Co Ltd 网站选购。
参考文献
  • [1]. Rabizadeh E, et al. Pivanex, a histone deacetylase inhibitor, induces changes in BCR-ABL expression and when combined with STI571, acts synergistically in a chronic myelocytic leukemia cell line. Leuk Res. 2007 Aug;31(8):1115-23. Epub 2007 Jan 30.

    [2]. Batova A, et al. The histone deacetylase inhibitor AN-9 has selective toxicity to acute leukemia and drug-resistant primary leukemia and cancer cell lines. Blood. 2002 Nov 1;100(9):3319-24.

    [3]. Edwards JD, et al. Effect of the Butyrate Prodrug Pivaloyloxymethyl Butyrate (AN9) on a Mouse Model for Spinal Muscular Atrophy. J Neuromuscul Dis. 2016 Nov 29;3(4):511-515.

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