佛波醇12-十四酸酯13-乙酸酯 | 16561-29-8

• 物质功能分类: 化学试剂 - 有机试剂 - 酯类
• 分子结构分类: 有机化合物 - 脂质和类脂质分子 - 异戊烯醇脂质
• 中文名称: 佛波醇12-十四酸酯13-乙酸酯
• 中文别名: 12-豆蔻酸-13-乙酸佛波醇；豆蔻酰佛波醇乙酯；乙酸佛波酯 PMA；乙酸佛波酯
• 英文名称: Phorbol 12-myristate 13-acetate
• 英文别名: [(1S,2S,6R,10S,11R,13S,14R,15R)-13-acetyloxy-1,6-dihydroxy-8-(hydroxymethyl)-4,12,12,15-tetramethyl-5-oxo-14-tetracyclo[8.5.0.02,6.011,13]pentadeca-3,8-dienyl] tetradecanoate
• CAS: 16561-29-8
• 化学式: C₃₆H₅₆O₈
• 分子量: 616.836
• InChiKey: PHEDXBVPIONUQT-RGYGYFBISA-N

物化性质

• 熔点：
  65-79oC
• 沸点：
  571.87°C (rough estimate)
• 密度：
  1.17±0.1 g/cm3 (20 ºC 760 Torr)
• 溶解度：
  可溶于DMSO，DMSO 溶液可以在20℃下避光保存至少六个月。
• 物理描述：
  12-o-tetradecanoylphorbol-13-acetate appears as white crystals. (NTP, 1992)
• 颜色/状态：
  Oil
• 蒸汽压力：
  1.8X10-17 mm Hg at 25 °C (est)
• 稳定性/保质期：
  Stable under recommended storage conditions.
• 分解：
  When heated to decomposition it emits acrid smoke and irritating fumes.
• 折光率：
  Index of refraction: 1.55 (est)
• 解离常数：
  pKa 12.6 at 25 °C (est)

计算性质

• 辛醇/水分配系数(LogP)：
  6.5
• 重原子数：
  44
• 可旋转键数：
  17
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.81
• 拓扑面积：
  130
• 氢给体数：
  3
• 氢受体数：
  8

ADMET

代谢

...TPA新陈代谢的主要途径是两个酯基的水解，...在啮齿动物皮肤模型中，所有水解产物都没有促进肿瘤的活性，这是TPA的主要毒理学效应。代谢水解需要酯酶的活性，不同组织和物种之间酯酶的活性不同。...TPA的两个酯基可以在小鼠皮肤和培养的细胞中被水解，产生单酯12-十四烷基佛波醇和醋酸-13-佛波醇，以及完全水解的产物，即佛波醇。在小鼠皮肤中，C-3位的酮基还原被确定为另一种代谢途径。 ...值得注意的是，在微粒体培养中没有检测到其他代谢物，这表明细胞色素450介导的氧化代谢不参与TPA的代谢。在各种培养细胞中观察到的唯一代谢反应也是酯基的水解。...。

...the major pathway in the metabolism of TPA is the hydrolysis of the two ester groups, ... in the rodent skin model all hydrolytic products lack tumor promoting activity, the major toxicological effect of TPA. The metabolic hydrolysis requires the activity of esterases, the activity of which differs between tissues and species. ... both ester groups of TPA can be hydrolysed in mouse skin and in cultured cells, giving rise to the monoesters 12-tetradecanoylphorbol and phorbol-13-acetate, as well as the product of complete hydrolysis, i.e. phorbol. Reduction of the keto group at C-3 was identified as a further metabolic pathway in mouse skin. ... Noteworthy, no other metabolites were detected in the microsomal incubations, suggesting that cytochrome 450-mediated oxidative metabolism is not involved in TPA metabolism. Ester group hydrolysis was also the only metabolic reaction observed in various cultured cells ... .

来源:Hazardous Substances Data Bank (HSDB)

代谢

... TPA的水解与诱导鸟氨酸脱羧酶（ODC）活性的丧失相平行。由于ODC是肿瘤促进的标志物，这些发现表明TPA的所有三种水解代谢物（两种单酯和佛波醇）都不具有肿瘤促进作用。在来自不同动物物种的培养成纤维细胞中，TPA及其结构类似物12,13-二癸酰佛波醇（PDD）的水解速率存在显著差异，这表明佛波醇二酯的水解代谢取决于细胞类型和二酯的化学结构...。

... the hydrolysis of TPA paralleled the loss of activity for induction of ornithine decarboxylase (ODC). As ODC is a marker for tumor promotion, these findings suggest that all three hydrolytic metabolites of TPA (the two monoesters and phorbol) are devoid of tumor promoting activity. Marked differences in the rate of hydrolysis of TPA and a structural analogue, phorbol-12,13-didecanoate (PDD) were observed between cultured fibroblasts from various animal species, suggesting that the hydrolytic metabolism of phorbol diesters depends on the cell type and on the chemical structure of the diester ... .

来源:Hazardous Substances Data Bank (HSDB)

代谢

...放射性标记的TPA在小鼠背部皮肤中的代谢被研究。除了水解代谢物外，还检测和鉴定了几种新的亲脂性代谢物，这些代谢物是TPA与长链脂肪酸在C-20羟基处形成的酯。这些TPA-20-酰化物似乎不具有促进肿瘤的活性，但在小鼠皮肤中部分水解回TPA。

... the metabolism of radiolabeled TPA /was studied/ in the back skin of mice in vivo. In addition to hydrolytic metabolites, several novel lipophilic metabolites were detected and identified as TPA esterified with long chain fatty acids at the C-20 hydroxyl group. These TPA-20-acylates appeared to be devoid of tumor promoting activity but were partly hydrolysed back to TPA in mouse skin ... .

来源:Hazardous Substances Data Bank (HSDB)

代谢

体外代谢研究中涉及人类细胞的TPA很少，表明在培养中许多人类细胞系并没有显著代谢TPA。

The few in vitro metabolism studies of TPA involving human cells indicate that many human cell lines in culture do not metabolize TPA to an appreciable extent ... .

来源:Hazardous Substances Data Bank (HSDB)

毒理性

• 毒性总结

识别和使用：TPA是一种无色粉末。它在癌症研究中用于研究肿瘤促进机制，筛选潜在的抑制剂，并作为肿瘤促进剂的阳性对照。它曾被测试用作治疗白血病、淋巴瘤和其他类型癌症的实验性药物。人类暴露和毒性：TPA是一种人类血小板聚集剂。TPA曾用于临床试验，针对患有复发性恶性肿瘤的人类，特别是包括严重白血病在内的血液恶性肿瘤。本次试验的目标是使用TPA作为在低剂量下诱导凋亡和细胞分化的剂。TPA的应用基于当前细胞毒性药物的方案，涉及35名患者在一定时间内接受低剂量恒速输注。在接受治疗后，各种患者出现了严重的副作用，如短暂的疲劳、贫血、中性粒细胞减少和血小板减少、轻度呼吸困难、恶心、发热、寒战以及心血管影响，包括晕厥和低血压，但只有一名患者表现出肿瘤反应，即肿块尺寸的减少。TPA通常用于体外人细胞研究。动物研究：TPA已被识别为小鼠皮肤生物检测和小鼠前胃以及在体外细胞增殖检测中的肿瘤促进剂。然而，没有证据表明TPA具有肿瘤起始特性。肿瘤起始和促进在小鼠的前胃上皮进行了研究，这些小鼠通过胃内给予单剂量的7,12-二甲基苯并[a]蒽（DMBA）50 mg TPA/kg bw，随后每周两次，连续35周给予TPA 10 mg/kg bw。在50只接受这种治疗的小鼠中，有45只前胃出现了肿瘤（乳头状瘤）。未处理对照组和仅接受TPA组的小鼠前胃未见肿瘤，尽管在仅接受DMBA组的小鼠中，10只小鼠前胃观察到乳头状瘤。TPA未显示为遗传毒性剂。TPA在某些实验系统中显示了裂变、突变和姐妹染色单体交换诱导效应，但这些效应是由细胞形成的次级产物（可能来自花生四烯酸）介导的，仅在培养基和血清中抗氧化剂含量低的培养条件下，对肿瘤促进剂的响应。当在整体大鼠胚胎培养中测试时，TPA暴露导致前脑减少、生长迟缓和身体轴向旋转不完全。培养后发现了大量的胚胎E-钙粘蛋白mRNA。TPA通常用于体外动物细胞研究。

IDENTIFICATION AND USE: TPA is a colorless powder. It is used in cancer research to study mechanisms of tumor promotion, to screen for potential inhibiting agents, and as positive control for tumor promoting agents. It has been tested as experimental medication for the treatment of leukemias and lymphomas and other types of cancer. HUMAN EXPOSURE AND TOXICITY: TPA is a human platelet aggregating agent. TPA was used in clinical trials in humans suffering from recurrent malignancies, particularly hematological malignancies including severe forms of leukemia. The objective of this trial was the use of TPA as an agent to induce, at low doses,apoptosis and cell differentiation. The TPA application was based on current protocols for cytostatic agents, and involved 35 patients given a low dose constant rate infusion over a defined period. Various patients developed severe side effects following the treatment, such as transient fatigue, anemia, neutropenia and thrombocytopenia, mild dyspnea, nausea fever, rigor and cardiovascular effects with syncope and hypotension, but only one patient exhibited a tumor response, consisting in a reduction in mass dimensions. TPA is routinely used in human cell studies in vitro. ANIMAL STUDIES: TPA has been recognized as a tumor promoter in a mouse skin bioassay and in the mouse forestomach as well as in in vitro cell proliferation assays. However, there was no evidence for tumor-initiating properties of TPA. Tumor initiation and promotion was investigated in the epithelium of the forestomach of mice treated intragastrically with a single dose of 7,12-dimethylbenz [a]anthracene(DMBA) at 50 mg TPA/kg bw followed by repeated dosing (twice per week) for 35 weeks of TPA at 10 mg/kg bw. Forty-five out of 50 mice which received this treatment had tumors (papillomas) in the forestomach. There were no forestomach tumors noted for mice in the untreated control and the TPA-only groups, although in the DMBA-only group, papillomas were observed in the forestomach of 10 mice. TPA was not demonstrated to be a genotoxicant. Clastogenic, mutagenic and sister chromatid exchange-inducing effects of TPA have been shown in some experimental systems but are mediated by secondary products (possibly from arachidonic acid) formed by the cell, only under culture conditions with low antioxidant content in culture media and sera, in response to the tumor promoter. When tested in whole rat embryo culture, TPA exposure led to reduced prosencephalon, growth retardation and incomplete axial rotation in the body. An abundance of embryonic E-cadherin mRNA was found after culture. TPA is routinely used in animal cell studies in vitro.

来源:Hazardous Substances Data Bank (HSDB)

毒理性

• 相互作用

为了确定在两阶段致癌过程中启动与促进之间的间隔以及小鼠老化对致癌的影响，一次将20微克的7,12-二甲基苯并(a)蒽（启动剂）应用于5组ICR/ha瑞士雌性小鼠的背部皮肤，每周3次应用2.5微克的PMA。对于1、2、3、4和5组，初次处理（启动剂）时的小鼠年龄（周）分别为6、44、56、6和6；次要处理（促进剂）的间隔（周）分别为2、2、2、36和56；每组的小鼠数量分别为120、20、50、35和35；长乳头状瘤的小鼠百分比分别为100、100、56、90和57；长鳞状细胞癌的小鼠百分比分别为50、30、6、25和11。适当的对照组由在各个时间间隔只给予一种药物的组组成。结果显示，无论启动与促进之间的间隔是2、36还是56周，都能诱导皮肤癌。当次要处理在小鼠58周和62周大时开始的3组和5组的癌症发生率显著较低。/来自表格/

To determine effect of interval between initiation & promotion & the effect of aging of mice in two-stage carcinogenesis, 20 ug 7,12-dimethylbenz(a)anthracene (initiator) was applied once only & 2.5 ug PMA was applied 3 times/wk to dorsal skin of 5 groups of female ICR/ha Swiss mice. For groups 1, 2, 3, 4 & 5, age (in wk) at primary treatment (initiator) was 6, 44, 56, 6 & 6 respectively; interval (in wk) to secondary treatment (promotor) was 2, 2, 2, 36 & 56 respectively; number of mice/group were 120, 20, 50, 35 & 35 respectively; % mice with papillomas was 100, 100, 56, 90 & 57 respectively; % mice with squamous carcinoma was 50, 30, 6, 25 & 11 respectively. Appropriate control groups consisted of one agent only given at various time intervals. Results show that skin carcinomas are induced whether interval between initiation & promotion is 2, 36 or 56 wk. Carcinoma incidences are significantly lower in groups 3 & 5 where secondary treatment was started when animals were 58 & 62 wk old. /From table/

来源:Hazardous Substances Data Bank (HSDB)

毒理性

• 相互作用

由于内源性蛋白酶可能在肿瘤促进剂的作用机制中发挥作用，因此测试了3种已知的蛋白酶抑制剂在两阶段致癌过程中的抑制效果。这些蛋白酶抑制剂包括甲苯磺酰氯甲基酮、甲苯磺酰苯丙氨酸氯甲基酮和甲苯磺酰精氨酸甲酯，在用7,12-二甲基苯并(a)蒽单次剂量引发小鼠耳朵肿瘤后，接着用PMA促进肿瘤发展时应用。抑制剂在促进剂应用后立即每周应用3次。蛋白酶抑制剂延迟了第一个肿瘤的出现，改变了肿瘤出现速率的一般模式，并导致肿瘤发生率有所下降。

Because endogenous proteases may play role in mechanism of action of tumor promotors, 3 known protease inhibitors were tested for ... inhibitory effects in two-stage carcinogenesis. Protease inhibitors ... tosyl chloromethyl ketone, tosyl phenylalanine chloromethyl ketone, & tosyl arginine methyl ester ... were applied to mouse ears after initiation with single dose of 7,12-dimethylbenz(a)anthracene followed by promotion with ... PMA. Inhibitors were applied 3 times/wk immediately after application of promoting agent. Protease inhibitors delayed appearance of 1st tumors, changed general pattern of rate of tumor appearance, & caused some decr in tumor incidences.

来源:Hazardous Substances Data Bank (HSDB)

毒理性

• 相互作用

硫化芥子气（bis(beta-chloroethyl)sulfide）的较低剂量完全抑制了小鼠皮肤的两阶段致癌作用。每组30只雌性ICR/ha小鼠分别接受对照处理或不同启动剂、促进剂和抑制剂测试组合的处理，持续400天。7,12-二甲基苯并(a)蒽 (DMBA)，20微克/0.1毫升丙酮，仅应用一次作为启动剂。促进剂PMA以2.5微克/0.1毫升丙酮的剂量每周应用三次。BCS（bis(beta-chloroethyl)sulfide），20微克/0.1毫升丙酮，在启动剂后14天开始应用。DMBA + PMA + BCS（每周两次）导致1只小鼠出现乳头状瘤，首次肿瘤发生在90天；DMBA + PMA + BCS（每周三次）导致2只小鼠出现乳头状瘤，发生在209天；仅DMBA + PMA处理导致27只小鼠出现乳头状瘤和16只出现鳞状细胞癌，发生在40天；仅PMA处理导致4只小鼠出现乳头状瘤，发生在218天；DMBA + BCS（每周两次）导致1只小鼠在385天出现乳头状瘤；DMBA + BCS（每周三次）没有产生乳头状瘤；仅BCS（每周三次）导致1只小鼠在323天出现乳头状瘤；仅DMBA + 丙酮的处理导致1只小鼠在219天出现乳头状瘤；对照组仅接受丙酮处理或未接受测试化合物处理的组没有观察到乳头状瘤。/来自表格/

Low dosages of sulfur mustard, bis(beta-chloroethyl)sulfide completely inhibited two-stage carcinogenesis in mouse skin. 30 Female ICR/ha mice per group received either control applications or different combinations of initiator, promotor & inhibitor test compd for 400 days. 7,12-Dimethylbenz(a)anthracene (DMBA), 20 ug/0.1 mL acetone, applied once only was used as initiator. PMA, the promotor, was applied at 2.5 ug/0.1 mL acetone 3 times/wk. BCS, bis(beta-chloroethyl)sulfide, at 20 ug/0.1 mL acetone was applied beginning 14 days after initiator. DMBA + PMA + BCS (2 times/wk) produced papillomas in 1 mouse with 1st tumor occurring at 90 days; DMBA + PMA + BCS (3 times/wk) produced papillomas in 2 mice occurring at 209 days; DMBA + PMA only produced papillomas in 27 mice & squamous cell carcinomas in 16 occurring at 40 days; PMA alone produced papillomas in 4 mice occurring at 218 days; DMBA + BCS (2 times/wk) produced papillomas in 1 mouse at 385 days; DMBA + BCS (3 times/wk) produced no papillomas; BCS alone (3 times/wk) produced papillomas in 1 mouse at 323 days; DMBA + acetone only produced papillomas in 1 mouse at 219 days; no papillomas were observed in control group admin acetone alone or in group which did not receive either of the test compd. /From table/

来源:Hazardous Substances Data Bank (HSDB)

毒理性

• 相互作用

本研究的目的旨在确定12-O-十四烷酰佛波醇-13-醋酸（TPA）和二乙基二硫代氨基甲酸（DDTC）单独或联合使用对体外培养的人胰腺癌细胞以及裸鼠体内生长的异种移植肿瘤的影响。胰腺癌细胞分别用DDTC或TPA单独处理，或者联合处理，然后通过台盼蓝排除法测定活细胞数量，通过形态学评估用碘化丙啶染色后在荧光显微镜下观察来确定凋亡细胞数量。DDTC或TPA单独处理以浓度依赖性方式抑制了胰腺癌细胞的生长并促进了其凋亡。与单独使用任一试剂相比，TPA与DDTC联合处理在PANC-1细胞的单层培养和三维（3D）培养中这些效果更为显著。联合处理对PANC-1细胞的显著效果与DDTC诱导的核因子-κB（NF-κB）激活抑制和Bcl-2表达降低有关，如通过NF-κB依赖性报告基因表达分析和西方印迹分析所示。此外，用DDTC + TPA处理裸鼠强烈抑制了PANC-1异种移植肿瘤的生长。本研究的结果表明，联合使用TPA和DDTC可能是抑制胰腺癌细胞生长的有效策略。

The aim of the present study was to determine the effects of 12-O-tetradecanoylphorbol-13-acetate (TPA) and diethyldithiocarbamate (DDTC) alone or in combination on human pancreatic cancer cells cultured in vitro and grown as xenograft tumors in nude mice. Pancreatic cancer cells were treated with either DDTC or TPA alone, or in combination and the number of viable cells was then determined by trypan blue ecxlusion assay and the number of apoptotic cells was determined by morphological assessment by staining the cells with propidium iodide and examining them under a fluorescence microscope. Treatment with DDTC or TPA alone inhibited the growth and promoted the apoptosis of pancreatic cancer cells in a concentration-dependent manner. These effects were more prominent following treatment with TPA in combination with DDTC than following treatment with either agent alone in PANC-1 cells in monolayer cultures and in 3 dimensional (3D) cultures. The potent effects of the combination treatment on PANC-1 cells were associated with the inhibition of nuclear factor-kappaB (NF-kappaB) activation and the decreased expression of Bcl-2 induced by DDTC, as shown by NF-kappaB-dependent reporter gene expression assay and western blot analysis. Furthermore, treatment of nude mice with DDTC + TPA strongly inhibited the growth of PANC-1 xenograft tumors. The results of the present study indicate that the administration of TPA and DDTC in combination may be an effective strategy for inhibiting the growth of pancreatic cancer.

来源:Hazardous Substances Data Bank (HSDB)

吸收、分配和排泄

...小鼠皮肤定位实验...确定了在皮肤涂抹放射性PMA后3-6小时内，基底层上方的角质层高度标记，皮脂腺和毛囊中度标记。48小时后，皮脂腺和毛囊中仍有一些标记。启动子的半衰期接近24小时。

...Mouse skin localization expt...determined that at 3-6 hr after skin application /with tritiated PMA/ the keratin layer just above basal cells was highly labeled, & sebaceous glands & hair follicles were moderately labeled. After 48 hr there was still some labeling in sebaceous glands & hair follicles. Half-life of...promoter was close to 24 hr.

来源:Hazardous Substances Data Bank (HSDB)

安全信息

• 危险等级：
  6.1(a)
• 危险品标志：
  Xi
• 安全说明：
  S36/37
• 危险类别码：
  R38
• WGK Germany：
  3
• 海关编码：
  29153900
• 危险品运输编号：
  2928
• 危险类别：
  6.1(a)
• RTECS号：
  QH4377000
• 包装等级：
  II
• 危险性防范说明：
  P201,P202,P260,P262,P264,P270,P271,P280,P284,P301+P310+P330,P302+P352+P310,P304+P340+P310,P305+P351+P338+P310,P308+P313,P332+P313,P361+P364,P403+P233,P405,P501
• 危险性描述：
  H300+H310+H330,H315,H318,H351
• 储存条件：
  库房应保持通风、低温和干燥，并将库存物品与食品分开储运。

SDS

Name:	Phorbol 12-myristate 13-acetate 99% Material Safety Data Sheet
Synonym:	PMA; TPA; 12-O-Tetradecanoylphorbol 13-acetat
CAS:	16561-29-8

Section 1 - Chemical Product MSDS Name:Phorbol 12-myristate 13-acetate 99% Material Safety Data Sheet
Synonym:PMA; TPA; 12-O-Tetradecanoylphorbol 13-acetat

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Section 2 - COMPOSITION, INFORMATION ON INGREDIENTS

CAS#	Chemical Name	content	EINECS#
16561-29-8	Phorbol 12-myristate 13-acetate	99%	unlisted

Hazard Symbols: T
Risk Phrases: 23/24/25

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Section 3 - HAZARDS IDENTIFICATION
EMERGENCY OVERVIEW
Toxic by inhalation, in contact with skin and if swallowed.Cancer suspect agent.
Potential Health Effects
Eye:
May cause eye irritation.
Skin:
Toxic in contact with skin.
Ingestion:
Poison by ingestion.
Inhalation:
Toxic if inhaled.
Chronic:
Not available.

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Section 4 - FIRST AID MEASURES
Eyes: Immediately flush eyes with plenty of water for at least 15 minutes, occasionally lifting the upper and lower eyelids. Get medical aid immediately.
Skin:
Get medical aid immediately. Immediately flush skin with plenty of water for at least 15 minutes while removing contaminated clothing and shoes.
Ingestion:
Get medical aid immediately. Wash mouth out with water.
Inhalation:
Remove from exposure and move to fresh air immediately. If not breathing, give artificial respiration. If breathing is difficult, give oxygen. Get medical aid.
Notes to Physician:

---

Section 5 - FIRE FIGHTING MEASURES
General Information:
As in any fire, wear a self-contained breathing apparatus in pressure-demand, MSHA/NIOSH (approved or equivalent), and full protective gear.
Extinguishing Media:
Use water spray, dry chemical, carbon dioxide, or chemical foam.

---

Section 6 - ACCIDENTAL RELEASE MEASURES
General Information: Use proper personal protective equipment as indicated in Section 8.
Spills/Leaks:
Vacuum or sweep up material and place into a suitable disposal container.

---

Section 7 - HANDLING and STORAGE
Handling:
Do not breathe dust, vapor, mist, or gas. Do not get in eyes, on skin, or on clothing. Use only in a chemical fume hood.
Storage:
Store in a cool, dry place. Store in a tightly closed container.
Deep freeze (below -20C).

---

Section 8 - EXPOSURE CONTROLS, PERSONAL PROTECTION
Engineering Controls:
Use adequate ventilation to keep airborne concentrations low.
Exposure Limits CAS# 16561-29-8: Personal Protective Equipment Eyes: Not available.
Skin:
Wear appropriate protective gloves to prevent skin exposure.
Clothing:
Wear appropriate protective clothing to prevent skin exposure.
Respirators:
Follow the OSHA respirator regulations found in 29 CFR 1910.134 or European Standard EN 149. Use a NIOSH/MSHA or European Standard EN 149 approved respirator if exposure limits are exceeded or if irritation or other symptoms are experienced.

---

Section 9 - PHYSICAL AND CHEMICAL PROPERTIES

Physical State: Solid
Color: colorless to white
Odor: Not available.
pH: Not available.
Vapor Pressure: Not available.
Viscosity: Not available.
Boiling Point: Not available.
Freezing/Melting Point: Not available.
Autoignition Temperature: Not available.
Flash Point: Not available.
Explosion Limits, lower: Not available.
Explosion Limits, upper: Not available.
Decomposition Temperature:
Solubility in water: Not available.
Specific Gravity/Density:
Molecular Formula: C36H56O8
Molecular Weight: 616.3872

---

Section 10 - STABILITY AND REACTIVITY
Chemical Stability:
Not available.
Conditions to Avoid:
Incompatible materials, light, excess heat.
Incompatibilities with Other Materials:
Strong oxidizing agents, strong bases.
Hazardous Decomposition Products:
Carbon monoxide, carbon dioxide.
Hazardous Polymerization: Will not occur.

---

Section 11 - TOXICOLOGICAL INFORMATION
RTECS#:
CAS# 16561-29-8: QH4377000 LD50/LC50:
Not available.
Carcinogenicity:
Phorbol 12-myristate 13-acetate - Not listed by ACGIH, IARC, or NTP.
Other:
See actual entry in RTECS for complete information.

---

Section 12 - ECOLOGICAL INFORMATION

---

Section 13 - DISPOSAL CONSIDERATIONS
Dispose of in a manner consistent with federal, state, and local regulations.

---

Section 14 - TRANSPORT INFORMATION

IATA
No information available.
IMO
No information available.
RID/ADR
No information available.

---

Section 15 - REGULATORY INFORMATION

European/International Regulations
European Labeling in Accordance with EC Directives
Hazard Symbols: T
Risk Phrases:
R 23/24/25 Toxic by inhalation, in contact with skin
and if swallowed.
Safety Phrases:
S 28A After contact with skin, wash immediately with
plenty of water.
S 36/37/39 Wear suitable protective clothing, gloves
and eye/face protection.
S 38 In case of insufficient ventilation, wear
suitable respiratory equipment.
S 45 In case of accident or if you feel unwell, seek
medical advice immediately (show the label where
possible).
WGK (Water Danger/Protection)
CAS# 16561-29-8: No information available.
Canada
None of the chemicals in this product are listed on the DSL/NDSL list.
CAS# 16561-29-8 is not listed on Canada's Ingredient Disclosure List.
US FEDERAL
TSCA
CAS# 16561-29-8 is not listed on the TSCA inventory.
It is for research and development use only.

---

SECTION 16 - ADDITIONAL INFORMATION
N/A

制备方法与用途

佛波酯又称佛波醇酯、大戟二萜醇酯，是巴豆油中的成分，十四烷酸和佛波醇形成的酯。已证实是一种促癌剂。其促癌活性大小不一，活性最高的是12-邻十四烷酰大戟二萜醇-13-乙酸酯（TPA），其余依次为大戟二萜醇-12,13-双癸酸酯、大戟二萜醇-12,13-双丁酸酯、4-邻甲基大戟二萜酸-12-十四烷酰-13-乙酸酯、大戟二萜醇-12,13-双癸酸酯。促癌机制不很清楚，近期认为与启动细胞膜相互作用，促进第二信使的合成和增加蛋白激酶活性有关。佛波酯能激活导致细胞增殖或分化的信号通路而具有促进细胞癌变的作用。

生物活性 Phorbol 12-肉豆蔻酸酯13-乙酸酯（PMA, 12-O-十四碳酰基佛波醇-13-乙酸酯，TPA）是一种有效的PKC激活剂，在纳摩尔浓度范围内具有活性作用。Phorbol 12-肉豆蔻酸酯13-乙酸酯（PMA）可诱导鞘氨醇-1-磷酸（S1P）。

靶点 PKC (11.7 nM EC50)

体外研究 为了探讨PKC在p38MAPK磷酸化中的作用，细胞用PKC激活剂PMA（100 nM）刺激，其模拟了DAG与PKCs C1区结合的天然活性。PMA在两种细胞类型中观察到p38MAPK磷酸化，类似于GnRH在αT3-1细胞中的观察结果，即缓慢持续的激活（分别为3.2倍和3.6倍，在30分钟时）。由GnRH和PMA激活的PKCs在p38MAPK磷酸化中表现出差异性作用的现象可由PKC的不同定位来解释。αT3-1细胞基线、GnRH-和PMA-刺激的p38MAPK磷酸化是由电压门控钙通道介导的钙内流和钙动员介导，而在分化后的LβT2促性腺激素细胞中仅由钙动员介导。THP-1细胞在200 ng/mL PMA（1-5天）的存在下被诱导分化为类似巨噬细胞的细胞（THP-1巨噬细胞），表现出形态学变化和CD11及CD14表面表达增加。

体内研究 PMA是PKC激动剂，可逆转5-羟基癸酸（5-HD）引起的损伤。因此，通过PKC途径激活的mitoKATP保护了SOD和MDA的线粒体功能。

类别 有毒物品

毒性分级 剧毒

急性毒性 静脉注射-小鼠LD50: 0.309 毫克/公斤

可燃性危险特性 可燃，火场排出辛辣刺激烟雾

储运特性 库房通风低温干燥；与食品分开储运

灭火剂 水、砂土、泡沫

反应信息

• 作为反应物：
  描述：

  佛波醇12-十四酸酯13-乙酸酯 在 咪唑 、 4-二甲氨基吡啶 、 potassium cyanide 、 三乙胺 作用下， 以 四氢呋喃 、 甲醇 、 二氯甲烷 、 N,N-二甲基甲酰胺 为溶剂， 生成
  参考文献：
  名称：

  荧光类生长抑素类似物的合成及生物学评价。

  摘要：

  为了研究促肿瘤的和非促肿瘤的bryostatin类似物的细胞分布，我们合成了两种bryostatin衍生物的荧光标记变体，它们先前已在U937白血病细胞中表现出佛波酯样或bryostatin样的生物活性。这些新的荧光类似物既显示出对蛋白激酶C（PKC）结合的高亲和力，又保留了U937分析中母体未标记化合物的基本特性。荧光化合物在细胞中显示出相似的细胞内分布模式。这与现有的假说相矛盾，该假说认为，细胞内分布的各种模式是生物活性差异的原因。进一步表征后，荧光化合物显示出缓慢的细胞摄取速率。相应地，

  DOI：

  10.1002/cbic.201700655
• 作为产物：
  描述：

  Phorbol-(12,13,20)-tri-n-tetradecanoat 生成 佛波醇12-十四酸酯13-乙酸酯
  参考文献：
  名称：

  克罗托诺尔斯的部分合成

  摘要：

  描述了在佛波醇的 α-二醇基团与乙酸和长链脂肪酸混合功能性佛波醇-(12,13)​​-二酯的部分合成。合成的六种佛波二酯与具有刺激性和促肿瘤作用的乙酰佛波酰化物 A 相同1- 一种4, 乙4和乙7从巴豆油中分离。异构佛波醇-(12,13)​​-二酯 A2和乙7以及ASA3和乙4是关于脂肪酸残基的位置异构体对。对于迄今为止从巴豆油中分离出来的所有 11 种佛波醇·(12,13)​​-二酯，A 基团的化合物在 C-13 处带有长链脂肪酸残基，在 C-13 处带有短链脂肪酸残基，这可以概括为-12。B组化合物显示这些脂肪酸残基的相反位置。A 型和 B 型的异构佛波二酯可以通过它们在薄层色谱中的 Rf 值、它们的 IR 和质谱以及它们的 20-[4'-硝基苯基偶氮苯甲酸-(4)]-酯的熔点来区分. 通过所描述的合成路线，具有确定化学结构的佛波醇-(12,13)​​-二酯现在很容易获得。

  DOI：

  10.1515/znb-1968-0422
• 作为试剂：
  描述：

  phosphatidyl choline 、 3-叠氮基丙醇 在 佛波醇12-十四酸酯13-乙酸酯 作用下， 生成
  参考文献：
  名称：

  CHEMICAL TOOLS FOR IMAGING PHOSPHOLIPASE D ACTIVITY

  摘要：

  一种检测细胞中磷脂酶D（PLD）活性的方法，包括：（i）刺激该细胞内源PLD，使其催化磷脂酰胆碱或其衍生物与外源官能化醇之间的转移磷酸基作用，形成磷脂醇，其中该官能化醇具有第一官能团，可以与具有第二官能团反应并形成键合的官能化可检测标记反应，并且该磷脂醇以可用形式包含所述的第一官能团；（ii）在所述官能化可检测标记反应的条件下，将所述磷脂醇与所述官能化可检测标记反应，通过其第二官能团与第一官能团反应形成链接，以形成包含所述可检测标记的标记磷脂醇；（iii）检测所述标记磷脂醇。

  公开号：

  US20190085373A1

文献信息

• Novel triterpene derivatives
  申请人：onepharm Research & Development GmbH

  公开号：EP2228380A1

  公开（公告）日：2010-09-15

  The present invention encompasses novel triterpene compounds of general formula I wherein R3a R3b R11a R11b R31 and R32 are defined as in claim 1, which are suitable for the prevention and/or treatment of diseases mediated by 11β-HSD and the use thereof for preparing a medicament having the above-mentioned properties.

  本发明涵盖了一般式I的新型三萜化合物， 其中 R3a、R3b、R11a、R11b、R31和R32如权利要求1所定义，适用于预防和/或治疗由11β-HSD介导的疾病，并用于制备具有上述特性的药物。
• Preparation of optically active 2-(1-hydroxyethyl)-5-hydroxynaphtho[2,3-b]furan-4, 9-diones having anticancer activities
  申请人：Iida Akira

  公开号：US20080300415A1

  公开（公告）日：2008-12-04

  An object of the present invention is to provide a method for efficiently preparing (S)-2-(1-hydroxyethyl)-5-hydroxynaphtho[2,3-b]-furan-4,9-dione useful as a medicine at a low cost and in large amounts. According to the present invention, the desired (S)-2-(1-hydroxyethyl)-5-hydroxynaphtho[2,3-b]furan-4,9-dione can be prepared with high efficiency at a low cost and in large amounts by asymmetrically reducing 2-acetyl-5-hydroxynaphtho[2,3-b]furan-4,9-dione in the presence of an asymmetric ruthenium complex and a hydrogen donor.

  本
• [EN] SMALL MOLECULE INHIBITORS OF ALDH AND USES THEREOF<br/>[FR] INHIBITEURS À PETITES MOLÉCULES D'ALDH ET UTILISATIONS ASSOCIÉES
  申请人：UNIV MICHIGAN REGENTS

  公开号：WO2017223086A1

  公开（公告）日：2017-12-28

  This invention is in the field of medicinal chemistry. In particular, the invention relates to a new class of small-molecules having a thiopyrimidinone structure which function as inhibitors of ALDH protein, and their use as therapeutics for the treatment of cancer and other diseases.

  这项发明属于药物化学领域。特别是，该发明涉及一类具有噻吩嘧啶酮结构的新颖小分子，它们作为ALDH蛋白的抑制剂，以及它们作为治疗癌症和其他疾病的疗法的使用。
• [EN] DITERPENOID COMPOUNDS THAT ACT ON PROTEIN KINASE C (PKC)<br/>[FR] COMPOSÉS DITERPÉNOÏDES AGISSANT SUR LA PROTÉINE KINASE C (PKC)
  申请人：K GEN INC

  公开号：WO2021062030A1

  公开（公告）日：2021-04-01

  This present disclosure relates to protein kinase C (PKC) modulating compounds, methods of treating a subject with cancer using the compounds, and combination treatments with a second therapeutic agent.

  本公开涉及蛋白激酶C（PKC）调节化合物，使用这些化合物治疗癌症患者的方法，以及与第二治疗剂联合治疗的方法。
• SPIRO-OXINDOLE MDM2 ANTAGONISTS
  申请人：Wang Shaomeng

  公开号：US20110112052A1

  公开（公告）日：2011-05-12

  Provided herein are compounds, compositions, and methods in the field of medicinal chemistry. The compounds and compositions provided herein relate to spiro-oxindoles which function as antagonists of the interaction between p53 and MDM2, and their use as therapeutics for the treatment of cancer and other diseases.

  本文提供了关于药物化学领域的化合物、组合物和方法。本文提供的化合物和组合物涉及作为p53和MDM2相互作用拮抗剂的螺环氧吲哌酮，并且它们作为治疗癌症和其他疾病的药物的用途。