4alpha-佛波醇12,13-二癸酸酯 | 27536-56-7

• 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: 4alpha-佛波醇12,13-二癸酸酯
• 中文别名: 4α-佛波醇-12,13-二癸酸
• 英文名称: 4α-phorbol-12,13-didecanoate
• 英文别名: 4αPDD；4α-phorbol 12,13-dicaprinate；4alpha-Phorbol 12,13-didecanoate；[(1S,2S,6S,10S,11R,13S,14R,15R)-13-decanoyloxy-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] decanoate
• CAS: 27536-56-7
• 化学式: C₄₀H₆₄O₈
• 分子量: 672.943
• InChiKey: DGOSGFYDFDYMCW-OEFRVDPMSA-N

物化性质

• 溶解度：
  可溶于DMSO

计算性质

• 辛醇/水分配系数(LogP)：
  8.5
• 重原子数：
  48
• 可旋转键数：
  21
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.82
• 拓扑面积：
  130
• 氢给体数：
  3
• 氢受体数：
  8

安全信息

• 危险等级：
  6.1(b)
• 危险品标志：
  T+
• 安全说明：
  S36/37/39,S45
• 危险类别码：
  R26/27/28,R40,R43
• 包装等级：
  III
• 危险类别：
  6.1(b)

反应信息

• 作为反应物：
  描述：

  4alpha-佛波醇12,13-二癸酸酯 以 乙醇 为溶剂， 反应 24.0h， 以95%的产率得到lumi-4α-phorbol 12,13-didecanoate
  参考文献：
  名称：

  Modulation of the Transient Receptor Potential Vanilloid Channel TRPV4 by 4α-Phorbol Esters: A Structure−Activity Study

  摘要：

  The mechanism of activation of the transient receptor potential vanilloid 4 (TRPV4) channel by 4 alpha-phorbol esters was investigated by combining information from chemical modification of 4 alpha-phorbol-didecanoate (4 alpha-PDD, 2a), site-directed mutagenesis, Ca2+ imaging, and electrophysiology. Binding of 4 alpha-phorbol esters occurs in a loop in the TM3-TM4 domain of TRPV4 that is analogous to the capsaicin binding site of TRPV1, and the ester decoration of ring C and the A,B ring junction are critical for activity. The lipophilic ester groups on ring C serve mainly as a steering element, affecting the orientation of the diterpenoid core into the ligand binding pocket, while the nature of the A,B ring junction plays an essential role in the Ca2+-dependence of the TRPV4 response. Taken together, our results show that 4 alpha-phorbol is a useful template to investigate the molecular details of TRPV4 activation by small molecules and obtain information for the rational design of structurally simpler ligands for this ion channel.

  DOI：

  10.1021/jm9001007

文献信息

• Method for Activating Trpv4 Channel Receptors by Agonists
  申请人：Kumar Sanjay

  公开号：US20070259856A1

  公开（公告）日：2007-11-08

  This invention relates to methods for activating a TRPV4 channel receptor, thereby reducing the production and/or release of matrix degrading enzymes by a cell expressing a TRPV4 channel receptor, thereby reducing the breakdown of an extra-cellular matrix. Also contemplated within the scope of the invention are methods of attenuating the inhibition of matrix production.

  本发明涉及激活TRPV4通道受体的方法，从而减少表达TRPV4通道受体的细胞产生和/或释放基质降解酶，从而减少细胞外基质的分解。本发明还考虑了减轻基质生产抑制的方法。
• Member of the ion channel family of polypeptides; vanilrep4
  申请人：SMITHKLINE BEECHAM PLC

  公开号：EP1170365A1

  公开（公告）日：2002-01-09

  VANILREP4 polypeptides and polynucleotides member of the ion channel family of polypeptides, and methods for producing such polypeptides by recombinant techniques are disclosed. Also disclosed are methods for utilizing VANILREP4 polypeptides and polynucleotides in diagnostic assays.

  本文公开了离子通道多肽家族成员 VANILREP4 多肽和多核苷酸，以及通过重组技术生产此类多肽的方法。还公开了在诊断测定中利用 VANILREP4 多肽和多核苷酸的方法。
• Means and methods for treating peripheral and cardiovascular diseases via modulation of arteriogenesis
  申请人：Max-Planck-Gesellschaft zur Förderung der Wissenschaften e.V.

  公开号：EP2030631A1

  公开（公告）日：2009-03-04

  The present invention relates to a pharmaceutical composition comprising (a) a polynucleotide comprising or consisting of a nucleotide sequence encoding a polypeptide with the amino acid sequence as set forth in SEQ ID NO: 2; (b) a polynucleotide comprising or consisting of a nucleotide sequence which is a fragment of a nucleotide sequence encoding the polypeptide with the amino acid sequence as set forth in SEQ ID NO: 2, wherein the polypeptide encoded by said polynucleotide has arteriogenic activity; (c) a polynucleotide comprising or consisting of a nucleotide sequence encoding a polypeptide, wherein said polypeptide exhibits at least 70% sequence identity with the sequence of the polypeptide encoded by the polynucleotide of (a) or (b) over the entire length, and wherein said polypeptide has arteriogenic activity; and/or (d) a polypeptide encoded by the polynucleotide of any one of (a) to (c).

  本发明涉及一种药物组合物，其包含(a)多核苷酸，该多核苷酸包含或由编码具有 SEQ ID NO: 2 所述氨基酸序列的多肽的核苷酸序列组成；(b)多核苷酸，该多核苷酸包含或由核苷酸序列组成，该核苷酸序列是编码具有 SEQ ID NO：2 所列氨基酸序列的核苷酸序列片段，其中所述多核苷酸编码的多肽具有动脉生成活性；(c) 包含或由编码多肽的核苷酸序列组成的多核苷酸，其中所述多肽与(a)或(b)的多核苷酸编码的多肽序列在整个长度上至少有 70% 的序列同一性，且所述多肽具有动脉生成活性；和/或 (d) (a)至(c)中任一项的多核苷酸编码的多肽。
• Alzheimer's disease-specific alterations of the ERK1/ERK2 phosphorylation ratio as Alzheimer's disease-specific molecular biomarkers (ADSMB)
  申请人：Blanchette Rockefeller Neurosciences Institute

  公开号：EP2031398A1

  公开（公告）日：2009-03-04

  The present invention relates to methods of diagnosing Alzheimer's Disease as well as to methods of confirming the presence or absence of Alzheimer's Disease in a subject. The present invention is also directed to methods of identifying a lead compound useful for the treatment of Alzheimer's Disease by contacting non-Alzheimer's cells with an amyloid beta peptide, stimulating the cells with a protein kinase C activator, contacting the cells with a test compound, and determining the value of an Alzheimer's Disease-specific molecular biomarker. The present invention is also directed to methods of diagnosing Alzheimer's Disease in a subject by detecting alterations in the ratio of specific phosphorylated MAP kinase proteins in cells after stimulation with a protein kinase C activator. The Alzheimer's Disease-specific molecular biomarkers disclosed herein are useful for the diagnosis of Alzheimer's Disease, monitoring the progression of Alzheimer's Disease in a subject and in screening methods for the identification of compounds for treating or preventing Alzheimer's Disease. The invention is also directed to kits containing reagents for the detection and diagnosis of the presence or absence of Alzheimer's Disease using the Alzheimer's Disease-specific molecular biomarkers disclosed herein.

  本发明涉及诊断阿尔茨海默病的方法以及确认受试者是否患有阿尔茨海默病的方法。本发明还涉及通过使非阿尔茨海默氏症细胞与淀粉样β肽接触、用蛋白激酶C激活剂刺激细胞、使细胞与测试化合物接触并确定阿尔茨海默氏症特异性分子生物标志物的值来鉴定治疗阿尔茨海默氏症的先导化合物的方法。本发明还涉及通过检测细胞在受到蛋白激酶 C 激活剂刺激后特定磷酸化 MAP 激酶蛋白比例的变化来诊断受试者阿尔茨海默氏症的方法。本发明公开的阿尔茨海默病特异性分子生物标志物可用于诊断阿尔茨海默病、监测阿尔茨海默病在受试者中的进展以及用于鉴定治疗或预防阿尔茨海默病的化合物的筛选方法。本发明还涉及含有试剂的试剂盒，该试剂盒用于使用本文公开的阿尔茨海默病特异性分子生物标记物检测和诊断是否存在阿尔茨海默病。
• PHARMACEUTICAL AGENT FOR PREVENTION AND TREATMENT OF SKIN DISEASE INDUCED BY ACCELERATED KERATINIZATION
  申请人：Kyoto University

  公开号：EP2127673A1

  公开（公告）日：2009-12-02

  A medicament for prophylactic and/or therapeutic treatment of a dermatosis resulting from excessively advanced keratinization, such as non-hereditary inflammatory keratosis and hereditary congenital keratosis, which comprises a substance selected from the group consisting of a cannabinoid agonist and a vanilloid agonist as an active ingredient.

  一种用于预防和/或治疗过度角化引起的皮肤病（如非遗传性炎症性角化病和遗传性先天性角化病）的药物，其活性成分包括一种从大麻素激动剂和香草素激动剂组成的组中选出的物质。