TUBASTATINA三氟乙酸盐 | 1239034-70-8

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯和取代衍生物
• 中文名称: TUBASTATINA三氟乙酸盐
• 英文名称: 4-(2-methyl-1,2,3,4-tetrahydro-pyrido[4,3-b]indol-5-ylmethyl)benzoic acid methyl ester
• 英文别名: methyl 4-((1,2,3,4-tetrahydro-2-methylpyrido[4,3-b]indol-5-yl)methyl)benzoate；4-(2-methyl-1,2,3,4-tetrahydropyrido[4,3-b]indol-5-ylmethyl)benzoic acid methyl ester；Methyl 4-((2-methyl-3,4-dihydro-1H-pyrido[4,3-b]indol-5(2H)-yl)methyl)benzoate；methyl 4-[(2-methyl-3,4-dihydro-1H-pyrido[4,3-b]indol-5-yl)methyl]benzoate
• CAS: 1239034-70-8
• 化学式: C₂₁H₂₂N₂O₂
• 分子量: 334.418
• InChiKey: RMAYYLGDIMEEOS-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.4
• 重原子数：
  25
• 可旋转键数：
  4
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.29
• 拓扑面积：
  34.5
• 氢给体数：
  0
• 氢受体数：
  3

安全信息

• 危险性防范说明：
  P280,P305+P351+P338
• 危险性描述：
  H302

反应信息

• 作为反应物：
  描述：

  TUBASTATINA三氟乙酸盐 在 羟胺 作用下， 生成 化合物TUBASTATINA
  参考文献：
  名称：

  HDAC6 inhibitor accelerates wound healing by inhibiting tubulin mediated IL-1β secretion in diabetic mice

  摘要：

  Delayed wound healing in diabetes is characterized by sustained activation of inflammasome and increased expression of IL-1 beta in macrophages. Identification and validation of novel pathways to regulate IL-1 beta expression will provide therapeutic targets for diabetic wounds. Here we report sustained over-expression of histone deacetylase 6 (HDAC6) in wounds of diabetic mice and its role in delayed wound healing. Topical application of HDAC6 inhibitor; Tubastatin A (TSA) gel promoted the wound healing in diabetic mice. TSA hydrogel reduced the infiltration of neutrophils, T-cells and macrophages in the early phase of wound healing. TSA treatment promoted the wound healing by inducing collagen deposition, angiogenesis (CD31) and fibrotic factors (TGF-beta 1) in the late phase of healing. Protein analysis of the diabetic wounds treated with TSA showed increased acetylated alpha-tubulin and decreased levels of mature IL-1 beta with no significant effect on the expression of pro-IL-1 beta, pro-caspase-1 and active caspase-1. In in vitro assays, macrophages exhibited upregulation of HDAC6, IL-1 beta and downregulation of IL-10 upon stimulation with high glucose and LPS. TSA inhibited the IL-1 beta secretion and promoted IL-10 in stimulated macrophages with high glucose and LPS. Further investigations showed that TSA inhibits IL-1 beta release by inhibiting tubulin dependent lysosomal exocytosis without affecting its transcription and maturation. Nocodazole (known acetylation inhibitor) pre-treatment inhibited TSA effect on IL-1 beta secretion in high glucose stimulated macrophages. Overall, our findings indicate that sustained HDAC6 expression in diabetic wounds contributes to impaired healing responses and HDAC6 may represent a new therapeutic target for diabetic wounds.

  DOI：

  10.1016/j.bbadis.2020.165903
• 作为产物：
  描述：

  苯肼 在 硫酸 、 potassium tert-butylate 作用下， 以 1,4-二氧六环 、 N,N-二甲基甲酰胺 为溶剂， 反应 2.25h， 生成 TUBASTATINA三氟乙酸盐
  参考文献：
  名称：

  [EN] HDAC INHIBITORS AND THERAPEUTIC METHODS USING THE SAME
  [FR] INHIBITEURS DE HDAC ET PROCÉDÉS THÉRAPEUTIQUES LES UTILISANT

  摘要：

  公开号：

  WO2011011186A3

文献信息

• HDAC INHIBITORS AND THERAPEUTIC METHODS OF USING SAME
  申请人：Kozikowski Alan

  公开号：US20120252740A1

  公开（公告）日：2012-10-04

  Histone deacetylases inhibitors (HDACIs) and compositions containing the same are disclosed. Methods of treating diseases and conditions wherein inhibition of HDAC provides a benefit, like a cancer, a neurodegenerative disorder, a neurological disease, traumatic brain injury, stroke, malaria, an autoimmune disease, autism, and inflammation, also are disclosed.

  本文披露了组蛋白去乙酰化酶抑制剂（HDACIs）及其含量。同时还披露了治疗疾病和状况的方法，其中抑制HDAC能够提供益处，如癌症、神经退行性疾病、神经系统疾病、创伤性脑损伤、中风、疟疾、自身免疫疾病、自闭症和炎症。
• HDAC Inhibitors and Therapeutic Methods of Using Same
  申请人：THE BOARD OF TRUSTEES OF THE UNIVERSITY OF ILLINOIS

  公开号：US20130281484A1

  公开（公告）日：2013-10-24

  Histone deacetylases inhibitors (HDACIs) and compositions containing the same are disclosed. Methods of treating diseases and conditions wherein inhibition of HDAC provides a benefit, like a cancer, a neurodegenerative disorder, a neurological disease, traumatic brain injury, stroke, malaria, an autoimmune disease, autism, and inflammation, also are disclosed.

  本文披露了组蛋白去乙酰化酶抑制剂（HDACIs）及其组合物。同时还披露了治疗疾病和状况的方法，其中抑制HDAC可以提供益处，例如癌症、神经退行性疾病、神经系统疾病、创伤性脑损伤、中风、疟疾、自身免疫疾病、自闭症和炎症。
• HDAC inhibitors and therapeutic methods of using same
  申请人：Kozikowski Alan

  公开号：US08431538B2

  公开（公告）日：2013-04-30

  Histone deacetylases inhibitors (HDACIs) and compositions containing the same are disclosed. Methods of treating diseases and conditions wherein inhibition of HDAC provides a benefit, like a cancer, a neurodegenerative disorder, a neurological disease, traumatic brain injury, stroke, malaria, an autoimmune disease, autism, and inflammation, also are disclosed.

  本发明公开了组蛋白去乙酰化酶抑制剂（HDACIs）及其组合物。还公开了治疗疾病和条件的方法，其中抑制HDAC提供益处，如癌症、神经退行性疾病、神经疾病、创伤性脑损伤、中风、疟疾、自身免疫性疾病、自闭症和炎症。
• Rational Design and Simple Chemistry Yield a Superior, Neuroprotective HDAC6 Inhibitor, Tubastatin A
  作者：Kyle V. Butler、Jay Kalin、Camille Brochier、Guilio Vistoli、Brett Langley、Alan P. Kozikowski

  DOI：10.1021/ja102758v

  日期：2010.8.11

  Structure-based drug design combined with homology modeling techniques were used to develop potent inhibitors of HDAC6 that display superior selectivity for the HDAC6 isozyme compared to other inhibitors. These inhibitors can be assembled in a few synthetic steps, and thus are readily scaled up for in vivo studies. An optimized compound from this series, designated Tubastatin A, was tested in primary cortical neuron cultures in which it was found to induce elevated levels of acetylated a-tubulin, but not histone, consistent with its HDAC6 selectivity. Tubastatin A also conferred dose-dependent protection in primary cortical neuron cultures against glutathione depletion-induced oxidative stress. Importantly, when given alone at all concentrations tested, this hydroxamate-containing HDAC6-selective compound displayed no neuronal toxicity, thus, forecasting the potential application of this agent and its analogues to neurodegenerative conditions.
• [EN] HDAC INHIBITORS AND THERAPEUTIC METHODS USING THE SAME<br/>[FR] INHIBITEURS DE HDAC ET PROCÉDÉS THÉRAPEUTIQUES LES UTILISANT
  申请人：UNIV ILLINOIS

  公开号：WO2011011186A3

  公开（公告）日：2011-05-26