resiniferatoxin | 57444-62-9

• 物质功能分类: 分析化学 - 标准品 - 药典标准品和杂质标准品
• 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: resiniferatoxin
• 英文别名: [(1R,2R,6R,10S,11R,15R,17R)-13-benzyl-6-hydroxy-4,17-dimethyl-5-oxo-15-prop-1-en-2-yl-12,14,18-trioxapentacyclo[11.4.1.01,10.02,6.011,15]octadeca-3,8-dien-8-yl]methyl 2-(4-hydroxy-3-methoxyphenyl)acetate
• CAS: 57444-62-9
• 化学式: C₃₇H₄₀O₉
• 分子量: 628.719
• InChiKey: DSDNAKHZNJAGHN-IHCAYWNCSA-N

物化性质

• 沸点：
  768.7±60.0 °C(Predicted)
• 密度：
  1.35±0.1 g/cm3(Predicted)
• 溶解度：
  在DMSO中水中的溶解度为至100mM，在乙醇中水中的溶解度为至50mM

计算性质

• 辛醇/水分配系数(LogP)：
  4.5
• 重原子数：
  46
• 可旋转键数：
  9
• 环数：
  7.0
• sp3杂化的碳原子比例：
  0.46
• 拓扑面积：
  121
• 氢给体数：
  2
• 氢受体数：
  9

ADMET

毒理性

• 毒性总结

树脂毒素（Resiniferatoxin）激活了一部分初级传入感觉神经元的香草酸受体，这些神经元参与痛觉传递（生理性疼痛的传递）。RTX导致感觉神经元的质膜上出现一种新型的离子通道，即瞬时受体电位香草酸1通道，使其对阳离子，尤其是钙离子的通透性增加。这引发了一种强烈的刺激效应，随后是脱敏和镇痛作用。

Resiniferatoxin activates the vanilloid receptor in a subpopulation of primary afferent sensory neurons involved in nociception (the transmission of physiological pain). RTX causes a novel ion channel in the plasma membrane of sensory neurons, the transient receptor potential vanilloid 1, to become permeable to cations, most particularly the calcium cation. This evokes a powerful irritant effect followed by desensitization and analgesia. (L1244)

来源:Toxin and Toxin Target Database (T3DB)

毒理性

• 致癌物分类

对人类不具有致癌性（未被国际癌症研究机构IARC列名）。

No indication of carcinogenicity to humans (not listed by IARC).

来源:Toxin and Toxin Target Database (T3DB)

毒理性

• 健康影响

树脂毒素是一种神经毒素，作用于参与痛觉感知的传入感觉神经。它引起强烈的刺激作用，随后是脱敏和镇痛。

Resiniferatoxin is a neurotoxin that targets afferent sensory neurons involved in nociception. It evokes a powerful irritant effect followed by desensitization and analgesia. (L1244)

来源:Toxin and Toxin Target Database (T3DB)

毒理性

• 暴露途径

口服（摄入）（L1817）；皮肤（L1817）

Oral (ingestion) (L1817) ; dermal (L1817)

来源:Toxin and Toxin Target Database (T3DB)

毒理性

• 症状

树脂毒素（Resiniferatoxin）引起强烈的刺激性效应，随后是脱敏和镇痛。

Resiniferatoxin evokes a powerful irritant effect followed by desensitization and analgesia. (L1244)

来源:Toxin and Toxin Target Database (T3DB)

安全信息

• 危险等级：
  6.1(a)
• 危险类别码：
  R35,R25
• 危险品运输编号：
  UN 2928 6.1/PG 2
• WGK Germany：
  3
• RTECS号：
  CY1633700
• 包装等级：
  II
• 危险类别：
  6.1(a)

反应信息

• 作为反应物：
  描述：

  resiniferatoxin 在 sodium tetrahydroborate 作用下， 以 乙醇 为溶剂， 反应 2.0h， 以60%的产率得到9,13,14-orthophenylacetyl-3β-hydroxyresiniferonyl 20-(4-hydroxy-3-methoxyphenylacetate)
  参考文献：
  名称：

  Similarities and Differences in the Structure−Activity Relationships of Capsaicin and Resiniferatoxin Analogues

  摘要：

  Structure-activity relationships in analogues of the irritant natural product capsaicin have previously been rationalized by subdivision of the molecule into three structural regions (A, B, and C). The hypothesis that resiniferatoxin (RTX), which is a high-potency ligand for the same receptor and which has superficial structural similarities with capsaicin, could be analogously subdivided has been investigated. The effects of making parallel changes in the two structural series have been studied in a cellular functional assay which is predictive of analgesic activity. Parallel structural changes in the two series lead to markedly different consequences on biological activity; the 3- and 4-position aryl substituents (corresponding to the capsaicin 'A-region') which are strictly required for activity in capsaicin analogues are not important in RTX analogues. The homovanillyl C-20 ester group in RTX (corresponding to the capsaicin 'B-region') is more potent than the corresponding amide, in contrast to the capsaicin analogues. Structural variations to the diterpene moiety suggest that the functionalized 5-membered diterpene ring of RTX is an important structural determinant for high potency. Modeling studies indicate that the 3D position of the alpha-hydroxy ketone moiety in the 5-membered ring is markedly different in the phorbol (inactive) analogues and RTX (active) series. This difference appears to be due to the influence of the strained ortho ester group in RTX, which acts as a local conformational constraint. The reduced activity of an analogue substituted in this region and the inactivity of a simplified analogue in which this unit is entirely removed support this conclusion.

  DOI：

  10.1021/jm960139d
• 作为产物：
  描述：

  在 吡啶 、 三乙烯二胺 、 2,6-二甲基吡啶 、 盐酸 、 4-二甲氨基吡啶 、 2,2'-联吡啶 、 selenium(IV) oxide 、 sodium tetrahydroborate 、 N-溴代丁二酰亚胺(NBS) 、 2-氮杂金刚烷-N-氧自由基 、 cerium(III) chloride heptahydrate 、 四丁基氟化铵 、 三正丁基氢锡 、 lead(IV) tetraacetate 、 sodium hexamethyldisilazane 、 乙酸酐 、 L-Selectride 、 sodium hydride 、 二异丁基氢化铝 、 碳酸氢钠 、 potassium carbonate 、 caesium carbonate 、 二甲基亚砜 、 三乙胺 、 间氯过氧苯甲酸 、 copper(l) chloride 、 lithium hexamethyldisilazane 、 1,1'-偶氮(氰基环己烷) 作用下， 以 四氢呋喃 、 甲醇 、 5,5-dimethyl-1,3-cyclohexadiene 、 正己烷 、 二氯甲烷 、 水 、 N,N-二甲基甲酰胺 、 氯苯 、 甲苯 、 乙腈 、 mineral oil 、 叔丁醇 、 苯 为溶剂， 反应 118.76h， 生成 resiniferatoxin
  参考文献：
  名称：

  通过自由基介导的三组分偶联和 7-内环化实现树脂毒素的全合成

  摘要：

  Resiniferatoxin (1) 属于 daphnane diterpenoid 家族，对 TRPV1 具有强烈的激动作用，TRPV1 是一种有害温度和化学刺激的传感器。1 的高密度氧化反式融合 5/7/6-三碳环（ABC 环）对化学合成提出了艰巨的挑战。在这里，我们报告了一种新的基于自由基的策略的开发，用于从三个组件组装 1：A 环 9、烯丙基锡烷 18b 和 C 环 17b。由 d-核糖衍生物 19 制备的 6 元 17b 被设计为具有笼状原酸酯结构，α-烷氧基硒化物作为自由基前体。用 18b、9 和 V-40 处理 17b 后，从 17b 生成了具有强反应性的 α-烷氧基桥头自由基，然后依次与 9 和 18b 偶联得到 16b。第一个自由基反应形成了受阻的 C9，A 环和 C 环之间的 10-连接并以立体选择性方式扩展 A 环上的 C4 链。在将 16b 衍生为 15 后，剩余的

  DOI：

  10.1021/jacs.7b10177

文献信息

• PHARMACEUTICAL COMPOSITION FOR TREATING CANCER COMPRISING TRYPSINOGEN AND CHYMOTRYPSINOGEN
  申请人：Propanc Pty Ltd

  公开号：EP3095458A1

  公开（公告）日：2016-11-23

  The present invention generally relates to pharmaceutical compositions containing a protease proenzyme and use thereof for treating cancer. The pharmaceutical compositions are directed to compositions comprising a protease proenzyme and an active agent, the composition being capable of providing a multi-functional approach for treating cancer. The pharmaceutical compositions are also directed to compositions comprising a first and a second protease proenzyme capable of activation at or near a surface of a tumour cell to enhance cell-to-cell adhesion of tumour cells, effect proteolysis of tumour cells, or induce tumour cell apoptosis, differentiation or immunorecognition, wherein the first protease proenzyme is chymotrypsinogen and the second protease proenzyme is trypsinogen. The pharmaceutical compositions are also directed to compositions comprising a first and second active agent each capable of inducing intracellular activity in tumour cells.

  本发明一般涉及含有蛋白酶原的药物组合物及其治疗癌症的用途。这些药物组合物涉及包含蛋白酶原和活性剂的组合物，该组合物能够提供治疗癌症的多功能方法。本发明的药物组合物还涉及包含第一和第二蛋白酶原的组合物，第一和第二蛋白酶原能够在肿瘤细胞表面或其附近活化，以增强肿瘤细胞的细胞间粘附性，影响肿瘤细胞的蛋白水解，或诱导肿瘤细胞凋亡、分化或免疫认知，其中第一蛋白酶原为糜蛋白酶原，第二蛋白酶原为胰蛋白酶原。该药物组合物还涉及包含第一和第二活性剂的组合物，每种活性剂都能诱导肿瘤细胞的细胞内活性。
• Methods for administration and methods for treating cardiovascular diseases with resiniferatoxin
  申请人：Board of Regents of the University of Nebraska

  公开号：US10729643B2

  公开（公告）日：2020-08-04

  There is disclosed a method for administration of a formulation of resiniferatoxin (RTX) to provide cardiac sympathetic afferent denervation when applied in an amount and concentration sufficient to chemically denervate vanilloid 1 receptor (TRPV1)-expressing CSAR (cardiac sympathetic afferent reflex) afferents. There is further disclosed a method for treating heart failure or hypertension and its related indications selected from the group consisting of increased sympatho-excitation, cardiac hypertrophy, increased left ventricular end diastolic pressure (LVEDP), lung edema, and combinations thereof, comprising administering an effective amount of RTX directly to a tissue site selected from the group consisting of epicardium, a T1-T4 dorsal root ganglion and intrathecally to the T1-T4 region of the spinal column.

  本发明公开了一种施用树脂松脂素（RTX）制剂的方法，该制剂的施用量和浓度足以通过化学方法使表达香草素 1 受体（TRPV1）的 CSAR（心脏交感传入反射）传入神经失神经支配。进一步公开了一种治疗心力衰竭或高血压及其相关适应症的方法，该方法选自交感兴奋增加、心脏肥大、左心室舒张末期压力（LVEDP）增加、肺水肿及其组合组成的组，包括将有效量的 RTX 直接施用到选自心外膜、T1-T4 背根神经节和脊柱 T1-T4 区鞘内注射组成的组的组织部位。
• Bisnorsesquiterpenoids from Euphorbia resinifera Berg. and an Expeditious Procedure to Obtain Resiniferatoxin from Its Fresh Latex
  作者：Ernesto Fattorusso、Virginia Lanzotti、Orazio Taglialatela-Scafati、Gian Cesare Tron、Giovanni Appendino

  DOI：10.1002/1099-0690(20021)2002:1<71::aid-ejoc71>3.0.co;2-c

  日期：2002.1

  The fresh latex of cultivated E. resinifera Berg. is a convenient source of the ultrapotent vanilloid resiniferatoxin, and a transesterification-reesterification procedure that substantially alleviates the hazards associated with the direct isolation of this obnoxious diterpenoid has been developed. Various known phorboid constituents of the diterpenoid fraction were obtained in pure form and have been spectroscopically characterized for the first time, while the non-diterpenoid fraction of the latex gave, besides some common triterpenoids, three new bisnorsesquiterpenes of the dihydroionol type. The structures of these compounds were established through a combination of spectroscopic data and chemical reactions.
• Adolf, W.; Hecker, E., Zeitschrift fur Naturforschung, B: Chemical Sciences, 1993, vol. 48, # 3, p. 364 - 368
  作者：Adolf, W.、Hecker, E.

  DOI：——

  日期：——
• SELECTIVE ABLATION OF PAIN-SENSING NEURONS BY ADMINISTRATION OF A VANILLOID RECEPTOR AGONIST
  申请人：Iadarola Michael J.

  公开号：US20100222385A1

  公开（公告）日：2010-09-02

  The present invention provides methods and kits for the selective ablation of pain-sensing neurons. The methods comprise administration of a vanilloid receptor agonist to a ganglion in an amount that causes death of vanilloid receptor-bearing neurons. Accordingly, the present invention provides methods of controlling pain and inflammatory disorders that involve activation of vanilloid receptor-bearing neurons.