12-O-tetradecanoyl phorbol-13-acetate
(Synonyms: 佛波酯; PMA; TPA; Phorbol myristate acetate) 目录号 : GN10444
一种PKC激活剂
Cas No.:16561-29-8
Sample solution is provided at 25 µL, 10mM.
12-O-tetradecanoyl phorbol-13-acetate (TPA) is an activator of ERK/MAPK with the concentration of 50μm [1].
ERK is an extracellular signal-regulated kinase and transfers signals from a receptor on the cell surface to DNA cooperated with MAPK. It is reported that ERK deficiency leads to the cell uncontrolled growth and is regarded as a target to cure cancers.
TPA is a potent ERK activator. When tested with A549 cells (human lung cancer cell line), TPA treatment led to an early, strong, and relatively transient ERK phosphorylation [2]. In mouse embryo fibroblasts from DUSP5 (+/+) mice, administration of TPA increased levels of ERK expression [3].
In transgenic (Eisuke) mice expressing a F?rster resonance energy transfer (FRET) biosensor for ERK, ERK activity was gradually stimulated upon topical TPA treatment and reached the peak approximately 6 hr later [1].
It is also reported that TPA treatment increased the accumulation of immature myeloid cells and the formation of papillomas during epidermal carcinogenesis (important in the tumor formation) when tested with S100A9 transgenic mice [4].
12-O-十四烷基芦丁酸-13-乙酰化物（TPA）是一种ERK/MAPK激活剂，浓度为50μm [1]。
ERK是一种细胞外信号调节激酶，它将来自细胞表面受体的信号传递到与MAPK合作的DNA上。据报道，ERK缺乏会导致细胞无法控制地增长，并被视为治疗癌症的目标。
TPA是一种强效的ERK激活剂。在使用人类肺癌细胞系A549进行测试时，TPA处理导致早期、强烈且相对短暂的ERK磷酸化[2]。在来自DUSP5（+/+）小鼠的胚胎成纤维细胞中，给予TPA会增加ERK表达水平[3]。
在表达ERK FRET生物传感器的转基因（Eisuke）小鼠中，经过局部TPA处理后，ERK活性逐渐被刺激，并在大约6小时后达到峰值[1]。
据报道，当与S100A9转基因小鼠一起测试时，TPA治疗增加了未成熟髓样细胞的积累和乳头状瘤的形成（在肿瘤形成中很重要）。
References:
[1]. Hiratsuka, T., et al., Intercellular propagation of extracellular signal-regulated kinase activation revealed by in vivo imaging of mouse skin. Elife, 2014. 4.
[2]. Refsnes, M., et al., Differential NF-kappaB and MAPK activation underlies fluoride- and TPA-mediated CXCL8 (IL-8) induction in lung epithelial cells. J Inflamm Res, 2014. 7: p. 169-85.
[3]. Rushworth, L.K., et al., Dual-specificity phosphatase 5 regulates nuclear ERK activity and suppresses skin cancer by inhibiting mutant Harvey-Ras (HRasQ61L)-driven SerpinB2 expression. Proc Natl Acad Sci U S A, 2014. 111(51): p. 18267-72.
[4]. Ortiz, M.L., et al., Immature myeloid cells directly contribute to skin tumor development by recruiting IL-17-producing CD4+ T cells. J Exp Med, 2015.
| Kinase experiment [1]: | |
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Kinase assays |
Protein kinase C was assayed by measuring the incorporation of 32P into H1 histone from [γ-32P]ATP. The standard reaction mixture (0.25 ml) contained 5 pmol of Tris/HCl at pH 7.5, 1.25 pmol of magnesium nitrate, 50 pg of H1 histone, 2.5 nmol of [γ-32P]ATP (5 to 15xl04 cpm/nmol), and 0.5 pg of protein kinase C. Phospholipid, diolein, phorbol esters, and Ca2+ were added as indicated in each experiment. All reagents were taken up in water which was prepared by a double distillation apparatus followed by passing through a Chelex 100 column to remove as much Ca2+ as possible. After incubation for 3 min at 30oC, the reaction was stopped by the addition of 25% trichloroacetic acid, and acid-precipitable materials were collected on a Toyo-Roshi membrane filter (pore size, 0.45 pm). The catalytic fragment of protein kinase C was assayed similarly except that Ca2+, phospholipid, and diolein were omitted. |
| Cell experiment [2]: | |
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Cell lines |
B-lymphocyte cell line |
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Preparation method |
The solubility of this compound in DMSO is >10 mM. General tips for obtaining a higher concentration: Please warm the tube at 37℃ for 10 minutes and/or shake it in the ultrasonic bath for a while. Stock solution can be stored below -20℃ for several months. |
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Reacting condition |
1 nM |
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Applications |
12-O-tetradecanoyl phorbol-13-acetate was used for the activation of PKC (protein kinase C) in cells. |
| Animal experiment [3]: | |
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Animal models |
Chemical skin carcinogenesis mice |
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Dosage form |
Twice weekly treatment (12.5 μg in 100 μL acetone) |
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Application |
12-O-tetradecanoyl phorbol-13-acetate was used to induce skin cancer in mice. |
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Other notes |
Please test the solubility of all compounds indoor, and the actual solubility may slightly differ with the theoretical value. This is caused by an experimental system error and it is normal. |
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References: [1] Castagna M, et al. Direct activation of calcium-activated, phospholipid-dependent protein kinase by tumor-promoting phorbol esters. J Biol Chem. 1982 Jul 10;257(13):7847-51. [2] Jensen WA, et al. Inhibition of protein kinase C results in decreased expression of bovine leukemia virus. J Virol. 1992 Jul;66(7):4427-33. [3] Rushworth LK, et al. Dual-specificity phosphatase 5 regulates nuclear ERK activity and suppresses skin cancer by inhibiting mutant Harvey-Ras (HRasQ61L)-driven SerpinB2 expression. Proc Natl Acad Sci U S A. 2014 Dec 23;111(51):18267-72. |
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| Cas No. | 16561-29-8 | SDF | |
| 别名 | 佛波酯; PMA; TPA; Phorbol myristate acetate | ||
| Canonical SMILES | CCCCCCCCCCCCCC(=O)OC1C(C2(C(C=C(CC3(C2C=C(C3=O)C)O)CO)C4C1(C4(C)C)OC(=O)C)O)C | ||
| 分子式 | C36H56O8 | 分子量 | 616 |
| 溶解度 | ≥ 112.9mg/mL in DMSO | 储存条件 | 4°C, protect from light |
| 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 | 1.6234 mL | 8.1169 mL | 16.2338 mL |
| 5 mM | 0.3247 mL | 1.6234 mL | 3.2468 mL |
| 10 mM | 0.1623 mL | 0.8117 mL | 1.6234 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。
Quality Control & SDS
- View current batch:
- Purity: >98.00%
- COA (Certificate Of Analysis)
- SDS (Safety Data Sheet)
- Datasheet