(1R,2S,6S,10S,11R,13R,14R,15R)-1,6,13,14-tetrahydroxy-8-(hydroxymethyl)-4,12,12,15-tetramethyltetracyclo[8.5.0.02,6.011,13]pentadeca-3,8-dien-5-one

• 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
• 英文名称: (1R,2S,6S,10S,11R,13R,14R,15R)-1,6,13,14-tetrahydroxy-8-(hydroxymethyl)-4,12,12,15-tetramethyltetracyclo[8.5.0.02,6.011,13]pentadeca-3,8-dien-5-one
• 化学式: C₂₀H₂₈O₆
• 分子量: 364.4
• InChiKey: QGVLYPPODPLXMB-VPGGEMSBSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  -0.8
• 重原子数：
  26
• 可旋转键数：
  1
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.75
• 拓扑面积：
  118
• 氢给体数：
  5
• 氢受体数：
  6

ADMET

代谢

厌氧培养条件下，用人类肠道细菌处理桐油中的佛波醇（1）产生了五种代谢物：异佛波醇（2）、脱氧佛波醇（3）、4beta,9alpha,20-三羟基-13,15-塞科-1,6,15-桐三烯-3,13-二酮（4）、4beta,9alpha,20-三羟基-15,16,17-三诺-1,6-桐二烯-3,13-二酮（5）以及4beta,9alpha,20-三羟基-14(13→12)-阿贝奥-12alphaH-1,6-桐二烯-3,13-二酮（6）。所有这些代谢物（2-6）通过光谱方法进行了鉴定和表征，包括二维（2D）-核磁共振。来自人类肠道的九种特定菌株显示出将1转化为这些代谢物的能力。

Anaerobic incubation of phorbol (1) from Croton tiglium with human intestinal bacteria afforded five metabolites: isophorbol (2), deoxyphorbol (3), 4beta,9alpha,20-trihydroxy-13,15-seco-1,6,15-tigliatriene-3,13-dione (4), 4beta,9alpha,20-trihydroxy-15,16,17-trinor-1,6-tigliadiene-3,13-dione (5) and 4beta,9a,20-trihydroxy-14(13-->12)-abeo-12alphaH-1,6-tigliadiene-3,13-dione (6). All these metabolites (2-6) were identified and characterized by spectroscopic means, including two-dimensional (2D)-NMR. Nine defined strains from the human intestine showed an ability to transform 1 to these metabolites.

来源:Hazardous Substances Data Bank (HSDB)

毒理性

• 相互作用

12-O-十四烷酰基佛波醇13-醋酸(I)和佛波醇(II)增加了N-甲基-N'-硝基-N-亚硝基胍和甲基氧化偶氮醇醋酸处理的V79中国仓鼠细胞培养中抗乌本苷突变体的恢复率。在两种情况下，I比II在促进突变体恢复方面更有效。

12-O-tetradecanoylphorbol 13-acetate (I) & phorbol (II) incr the recovery of ouabain-resistant mutants in N-methyl-N'-nitro-N-nitrosoguanidine- and methylazoxyethanol acetate-treated V79 chinese hamster cell cultures. In both cases I was more effective than II in promoting the mutant recovery.

来源:Hazardous Substances Data Bank (HSDB)

毒理性

• 相互作用

皮肤肿瘤促进机制的研究。在雌性小鼠中，先用7,12-二甲基苯并[a]蒽(DMBA)启动后，同时给予佛波醇和12-O-十四烷基佛波醇-13-醋酸盐对促进过程没有影响。

Studies on the mechanism of skin tumor promotion. Phorbol given simultaneously with 12-o-tetradecanoylphorbol 13-acetate after 7,12-dimethylbenz[a]anthracene (DMBA) initiation in female mice had no effect on promotion.

来源:Hazardous Substances Data Bank (HSDB)

毒理性

• 相互作用

将200微居里的((3)H)-胸腺嘧啶单次皮下注射到怀孕的BALB/c小鼠中，随后每周两次腹腔注射佛波醇，持续25周，结果在后代中，雄性小鼠的肺和肝脏肿瘤发生率高于未处理的同窝小鼠，雌性小鼠的肿瘤发生率也有所提高，但程度较轻。总体肿瘤发生率差异有统计学意义，但单个肿瘤类型的增加仅具有边缘显著性。在未经佛波醇处理的母鼠和后代中观察到((3)H)胸腺嘧啶轻微的致癌活性。((3)H)-胸腺嘧啶可能作为广谱启动剂用于跨胎盘的两阶段致癌性研究，以确定不同促进剂的器官特异性。

A single s.c. injection of 200 uCi ((3)H)-thymidine into pregnant BALB/c mice followed by i.p. injections of phorbol twice weekly for 25 wk, in the offspring, resulted in higher tumor development in the lungs and livers of male and, to a lesser extent, of female offspring, than in their untreated littermates. The difference in overall tumor incidence was statistically significant, but the increases of the individual tumor types were only of borderline significance. Slight carcinogenic activity of ((3)H)thymidine alone was observed in the mothers and in the offspring without phorbol treatment. ((3)H)-thymidine may be useful as a broad spectrum initiator for transplacental 2-stage carcinogenicity studies to determine the organ specificity of different promoting agents.

来源:Hazardous Substances Data Bank (HSDB)

毒理性

• 相互作用

每周两次腹腔注射4毫克佛波醇，持续10周，在雌性Wistar大鼠单次喂养6毫克二甲基苯并(a)蒽（DMBA）之后，与单独使用6毫克DMBA相比，显著增加了乳腺腺癌的发生率和淋巴白血病的发病率。在雌性Sprague-Dawley大鼠中，使用相同剂量的DMBA和佛波醇以及相同的注射计划，佛波醇在DMBA之后给药并没有增加乳腺腺癌的发生率或淋巴白血病的发病率，与单独给予DMBA相比。在Wistar和Sprague-Dawley大鼠之间，对于佛波醇在DMBA治疗后的促癌活性存在菌株相关的敏感性，当研究乳腺腺癌的发生率和淋巴白血病的发病率时。佛波醇并没有促进DMBA处理大鼠的乳腺纤维腺瘤发生率，也没有促进丙卡巴肼处理大鼠的乳腺腺癌发生率，以及X射线处理大鼠的乳腺腺癌发生率或乳腺纤维腺瘤发生率。DMBA和丙卡巴肼，无论是否加用佛波醇，都倾向于在前部（胸腺）乳腺腺体中诱导更多的乳腺肿瘤，而不是在后部（腹部）乳腺腺体中。X射线照射倾向于在前部和后部乳腺腺体中诱导大致相等数量的乳腺肿瘤。化学诱导的乳腺致癌作用的区域性差异是由于化学致癌物向该区域的运输和递送差异，而不是该区域乳腺腺体组织的数量差异。分析Sprague-Dawley大鼠对DMBA、丙卡巴肼和X射线的反应，这些大鼠没有发生乳腺肿瘤，或者只发生乳腺腺癌，或者只发生乳腺纤维腺瘤，或者同时发生乳腺腺癌和乳腺纤维腺瘤的数量，表明乳腺腺癌的发展或乳腺纤维腺瘤的发展是独立的过程。

Twice-weekly i.p. injections of 4 mg phorbol for 10 wk, after a single feeding of 6 mg dimethylbenz(a)anthracene (DMBA) in female Wistar rats, led to a significant augmentation of mammary adenocarcinoma incidence and of lymphatic leukemia incidence as compared to 6 mg DMBA alone. In female Sprague-Dawley rats, using the same doses of DMBA and phorbol and the same injection schedule, phorbol given after DMBA did not augment mammary adenocarcinoma incidence or lymphatic leukemia incidence as compared to DMBA given alone. There is a strain-related sensitivity between Wistar and Sprague-Dawley rats with regard to the promoting activity of phorbol when phorbol treatment follows DMBA treatment, and mammary adenocarcinoma incidence and lymphatic leukemia incidence are studied. Phorbol did not promote mammary fibroadenoma incidence in DMBA-treated rats, mammary adenocarcinoma incidence in procarbazine-treated rats and mammary adenocarcinoma incidence or mammary fibroadenoma incidence in X-ray-treated rats. DMBA and procarbazine, with or without phorbol, tended to induce more mammary neoplasms in the anterior (thoracic) than in the posterior (abdominal) mammary glands. X-Irradiation tended to induce mammary neoplasms in approximately equal numbers in the anterior and posterior mammary glands. Regional differences in chemically induced mammary carcinogenesis were due to a difference in the transport and delivery of the chemical carcinogens to the regions rather than a difference in the amount of mammary gland tissue in the regions. An analysis of the numbers of Sprague-Dawley rats that developed either no mammary neoplasms, or only mammary adenocarcinomas, or only mammary fibroadenomas, or both mammary adenocarcinomas and mammary fibroadenomas in response to DMBA, procarbazine and X-ray, suggested that the development of a mammary adenocarcinoma or the development of a mammary fibroadenoma are independent processes.

来源:Hazardous Substances Data Bank (HSDB)

毒理性

• 毒性总结

识别和使用：佛波醇是一种粉末，用于生物化学和医学研究。人类暴露和毒性：佛波醇缺乏在佛波酯中发现的淋巴细胞激活诱导性质。与佛波酯不同，佛波醇缺乏促肿瘤活性，在抑制人类黑色素瘤细胞的生长和刺激分化功能方面要么无效要么反应很差。动物研究：佛波醇（20微克/毫升）无生物活性，对从小鼠大脑制备的受体结合位点无影响。佛波醇未能在器官培养中刺激新生小鼠颅骨的骨前列腺素E2合成和骨吸收。佛波醇在Friend病毒转化的前红细胞C1 745细胞中未显示出红细胞分化。因此，佛波醇是佛波酯的无活性类似物。

IDENTIFICATION AND USE: Phorbol is a powder. It is used in biochemical and medical research. HUMAN EXPOSURE AND TOXICITY: Phorbol lacked the lymphocyte-activating inducing properties found in phorbol esters. Unlike phorbol esters, phorbol lacks tumor-promoting activity and it was either inactive or elicited poor response in inhibition of growth and stimulation of differentiated functions in human melanoma cells. ANIMAL STUDIES: Phorbol (20 ug/mL) was devoid of biological activity and had no effect on binding sites in prepn from mouse brain. Phorbol did not stimulate prostaglandin E2 synthesis in bone and bone resorption in neonatal mouse calvaria in organ culture. Phorbol showed no erythroid differentiation in Friend virus-transformed proerythroid C1 745 cells. Thus phorbol is inactive analog of phorbol esters.

来源:Hazardous Substances Data Bank (HSDB)

文献信息

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