HDAC/Histone Deacetylases

体外活性：Phenylbutyrate 是一种众所周知的 HDAC 抑制剂，可增加多种基因的基因转录，并发挥神经保护作用。丁酸苯酯可显着减弱 MPTP 诱导的纹状体多巴胺消耗和黑质中酪氨酸羟化酶阳性神经元的丧失。 Phenylbutyrate 可减弱前列腺癌细胞中凋亡拮抗剂 Bcl-X(L)、双链断裂修复蛋白 DNA 依赖性蛋白激酶、前列腺进展标记 Caveolin-1 和促血管生成的血管内皮生长因子的表达。发现丁酸苯酯与电离辐射协同作用，诱导前列腺癌细胞凋亡。细胞测定：简而言之，将通过台盼蓝染料排除法判断的活细胞以 4 × 104 个细胞/mL 的密度接种在装有 RPMI 1640 的 60 mm 培养皿中，底层含有 10% 胎牛血清和 0.35% 琼脂糖0.7% 琼脂糖。 DMSO、TSA 或 PB 添加到底部和顶部琼脂糖层中。测定至少在三个不同的场合一式三份进行，并在 10-14 天时对菌落进行计数。

丁酸苯酯可显着延长 G93A 转基因 ALS 小鼠的生存期并改善其临床和神经病理表型。苯丁酸给药可改善 G93A 小鼠中观察到的组蛋白低乙酰化，并诱导核因子 kappaB (NF-kappaB) p50、NF-kappaB 的磷酸化抑制亚基 (pIkappaB) 和 β 细胞淋巴瘤 2 (bcl-2) 的表达，但会降低细胞色素 c和半胱天冬酶表达。 Phenylbutyrate 可磷酸化 IkappaB，将 NF-kappaB p50 转位至细胞核，或直接乙酰化 NF-kappaB p50。在亨廷顿病 (HD) 转基因小鼠模型中通过免疫细胞化学和蛋白质印迹评估，苯丁酸会增加脑组蛋白乙酰化并降低组蛋白甲基化水平。丁酸苯酯可增加泛素-蛋白体途径成分的 mRNA，并下调与凋亡细胞死亡有关的 caspase，以及纹状体中的活性 caspase 3 免疫反应性。

苯丁酸酯(PB)是一种组蛋白去乙酰化酶抑制剂，已被证明可诱导多种癌细胞的分化和凋亡。虽然这些影响很可能是由于基因表达的调节，但导致PB影响的特定基因和基因产物尚未得到很好的表征。在本研究中，我们使用cDNA表达阵列和Western blot来评估PB对各种癌症和凋亡调控基因产物表达的影响。我们发现，PB可以减弱细胞凋亡拮抗剂Bcl-X(L)、双链断裂修复蛋白dna依赖性蛋白激酶、前列腺进展标志物caveolin-1和促血管生成血管内皮生长因子的表达。此外，还发现PB与电离辐射协同作用可诱导前列腺癌细胞凋亡。综上所述，我们的研究结果表明，当与放疗或化疗联合使用并抑制癌症进展时，PB可能是一种有效的抗前列腺癌药物。[2]

简而言之，将活细胞以 4 × 10⁴ 细胞/mL 的密度接种在装有 10% 胎牛血清和 0.35% 琼脂糖的 RPMI 1640 的 60 毫米培养皿中，基础层为 0.7%琼脂糖。通过台盼蓝染料排除法确定活细胞。向上下琼脂糖层添加 DMSO、TSA 或 PB。 10-14 天后对菌落进行计数，并一式三份地进行至少三次测定。

Effects During Pregnancy and Lactation
◉ Summary of Use during Lactation
No information is available on the clinical use of sodium phenylbutyrate or the combination of sodium phenylbutyrate and taurursodiol during breastfeeding. Both sodium phenylbutyrate and taurursodiol are highly protein bound and therefore unlikely to enter milk in clinically important amounts. If sodium phenylbutyrate with or without taurursodiol is required by the mother, it is not a reason to discontinue breastfeeding. Until more data become available, these products should be used with caution during breastfeeding, especially while nursing a newborn or preterm infant. Monitoring the breastfed infant for neurotoxicity (excessive sedation, vomiting) during maternal therapy may be advisable.
◉ Effects in Breastfed Infants
Relevant published information was not found as of the revision date.
◉ Effects on Lactation and Breastmilk
Relevant published information was not found as of the revision date.

[1]. Neuromolecular Med. 2004;5(3):235-41.

[2]. Neoplasia. 2001 Jul-Aug;3(4):331-8.

[3]. J Neurochem. 2005 Jun;93(5):1087-98.

[4]. J Biol Chem. 2005 Jan 7;280(1):556-63.

[5]. Cell Death Dis. 2021 Oct 29;12(11):1016.

[6]. Front Neurol. 2017 Jun 9:8:256.

Sodium phenylbutyrate is the organic sodium salt of 4-phenylbutyric acid. A prodrug for phenylacetate, it is used to treat urea cycle disorders. It has a role as a prodrug, an EC 3.5.1.98 (histone deacetylase) inhibitor, a neuroprotective agent, an orphan drug and a geroprotector. It contains a 4-phenylbutyrate.
Sodium Phenylbutyrate is the sodium salt of phenylbutyrate, a derivative of the short-chain fatty acid butyrate, with potential antineoplastic activity. Phenylbutyrate reversibly inhibits class I and II histone deacetylases (HDACs), which may result in a global increase in gene expression, decreased cellular proliferation, increased cell differentiation, and the induction of apoptosis in susceptible tumor cell populations.
See also: Phenylbutyric acid (has active moiety); Sodium phenylbutyrate; taurursodiol (component of).

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Drug Indication
Ammonaps is indicated as adjunctive therapy in the chronic management of urea cycle disorders, involving deficiencies of carbamylphosphate synthetase, ornithine transcarbamylase orargininosuccinate synthetase. It is indicated in all patients with neonatal-onset presentation (complete enzyme deficiencies, presenting within the first 28 days of life). It is also indicated in patients with late-onset disease(partial enzyme deficiencies, presenting after the first month of life) who have a history of hyperammonaemic encephalopathy.
Treatment of chronic management of urea-cycle disorders.

C10H11O2.NA

186.18

186.065

C, 64.51; H, 5.96; Na, 12.35; O, 17.19

1716-12-7

1821-12-1 (free acid); 1716-12-7 (Sodium) 4-Phenylbutyric acid-d11;358730-86-6;4-Phenylbutyric acid-d5;64138-52-9;4-Phenylbutyric acid-d2;461391-24-2

5258

White to off-white solid powder

1.095g/cm3

290.7ºC at 760mmHg

207 °C (dec.)(lit.)

187.9ºC

0.00288mmHg at 25°C

0.759

40.13

0

2

4

13

142

0

[Na+].[O-]C(C([H])([H])C([H])([H])C([H])([H])C1C([H])=C([H])C([H])=C([H])C=1[H])=O

VPZRWNZGLKXFOE-UHFFFAOYSA-M

InChI=1S/C10H12O2.Na/c11-10(12)8-4-7-9-5-2-1-3-6-9;/h1-3,5-6H,4,7-8H2,(H,11,12);/q;+1/p-1

sodium;4-phenylbutanoate

2934.99.9001

Powder      -20°C    3 years

                     4°C     2 years

In solvent   -80°C    6 months

                  -20°C    1 month

注意： 请将本产品存放在密封且受保护的环境中，避免吸湿/受潮。

Room temperature (This product is stable at ambient temperature for a few days during ordinary shipping and time spent in Customs)

配方 1 中的溶解度: 100 mg/mL (537.11 mM) in PBS (这些助溶剂从左到右依次添加，逐一添加), 澄清溶液; 超声助溶。

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请根据您的实验动物和给药方式选择适当的溶解配方/方案：
1、请先配制澄清的储备液(如：用DMSO配置50 或 100 mg/mL母液(储备液));
2、取适量母液，按从左到右的顺序依次添加助溶剂，澄清后再加入下一助溶剂。以 下列配方为例说明 (注意此配方只用于说明，并不一定代表此产品 的实际溶解配方):
10% DMSO → 40% PEG300 → 5% Tween-80 → 45% ddH2O (或 saline);
假设最终工作液的体积为 1 mL, 浓度为5 mg/mL: 取 100 μL 50 mg/mL 的澄清 DMSO 储备液加到 400 μL PEG300 中，混合均匀/澄清；向上述体系中加入50 μL Tween-80，混合均匀/澄清；然后继续加入450 μL ddH2O (或 saline)定容至 1 mL；
3、溶剂前显示的百分比是指该溶剂在最终溶液/工作液中的体积所占比例;
4、 如产品在配制过程中出现沉淀/析出，可通过加热(≤50℃)或超声的方式助溶;
5、为保证最佳实验结果，工作液请现配现用！
6、如不确定怎么将母液配置成体内动物实验的工作液，请查看说明书或联系我们;
7、 以上所有助溶剂都可在 Invivochem.cn网站购买。