化合物TUBASTATINA | 1252003-15-8

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 吲哚及其衍生物
• 中文名称: 化合物TUBASTATINA
• 中文别名: TubastatinA抑制剂；TUBASTATIN-A游离态
• 英文名称: tubastatin A
• 英文别名: tubastatin；N-hydroxy-4-[(2-methyl-3,4-dihydro-1H-pyrido[4,3-b]indol-5-yl)methyl]benzamide
• CAS: 1252003-15-8
• 化学式: C₂₀H₂₁N₃O₂
• 分子量: 335.406
• InChiKey: GOVYBPLHWIEHEJ-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.3
• 重原子数：
  25
• 可旋转键数：
  3
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.25
• 拓扑面积：
  57.5
• 氢给体数：
  2
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  化合物TUBASTATINA 、 2-氯-4-硝基苯基-beta-D-葡糖-吡喃糖苷 在 尿苷-5’-二磷酸 、 magnesium chloride 作用下， 以 aq. buffer 为溶剂， 生成
  参考文献：
  名称：

  OleD Loki作为异羟肟酸酯糖基化催化剂。

  摘要：

  在本文中，我们描述了允许的糖基转移酶（GT）OleD Loki将15种以上的组蛋白脱乙酰基酶（HDAC）抑制剂（HDACis）转变为相应的异羟肟酸酯糖基酯的能力。随后在试验中评估了代表性的糖基酯的癌细胞系细胞毒性，化学和酶稳定性，以及olo胚尾部再生。计算底物对接模型可预测酶催化的转换，并暗示某些HDACis可能与GT形成非生产性的，潜在的抑制性复合物。

  DOI：

  10.1002/cbic.201900601
• 作为产物：
  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

文献信息

• [EN] ISOFORM-SELECTIVE LYSINE DEACETYLASE INHIBITORS<br/>[FR] INHIBITEURS DE LYSINE DÉSACÉTYLASE SÉLECTIFS ENVERS LES ISOFORMES
  申请人：UNIV WASHINGTON

  公开号：WO2016179398A1

  公开（公告）日：2016-11-10

  Isoform-selective lysine deacetylase inhibitors are described. Inhibitors of the lysine deacetylase enzyme are useful as antitumor drugs and for treating addiction, asthma, cardio-vascular disease, immunosuppression, neurodegenerative diseases, sepsis, sickle-cell disease, uveal melanoma and termination of viral latency, particularly HIV-1 latency.

  描述了选择性异构体赖氨酸去乙酰化酶抑制剂。赖氨酸去乙酰化酶的抑制剂可用作抗肿瘤药物，治疗成瘾、哮喘、心血管疾病、免疫抑制、神经退行性疾病、败血症、镰刀细胞病、葡萄膜黑色素瘤以及终止病毒潜伏，尤其是HIV-1潜伏。
• [EN] SELECTIVE HISTONE DEACTYLASE 6 INHIBITORS<br/>[FR] INHIBITEURS SÉLECTIFS D'HISTONE DÉSACÉTYLASE 6
  申请人：H LEE MOFFITT CANCER CT & RES

  公开号：WO2013134467A1

  公开（公告）日：2013-09-12

  Disclosed are selective histone deactylase inhibitors (HDACi) that having Formula (I). Methods of making and using these inhibitors for the treatment of cancer, in particular melanoma are also disclosed.

  披露了具有化学式（I）的选择性组蛋白去乙酰化酶抑制剂（HDACi）。还披露了制备和使用这些抑制剂用于治疗癌症，特别是黑色素瘤的方法。
• [EN] HDAC6 INHIBITORS AND USES THEREOF<br/>[FR] INHIBITEURS DE HDAC6 ET LEURS UTILISATIONS
  申请人：UNIV GENT

  公开号：WO2014147178A1

  公开（公告）日：2014-09-25

  The present invention relates to Histone deacetylases 6 (HDAC6) inhibitors and compositions containing the same. Methods of treating diseases and conditions wherein inhibition of HDAC6 provides a benefit, like a cell proliferative disease, an autoimmune or inflammatory disorder, a neurodegenerative disease, a viral disease, malaria, or a combination thereof, also are disclosed.

  本发明涉及组蛋白去乙酰化酶6（HDAC6）抑制剂及含有该抑制剂的组合物。还公开了通过抑制HDAC6提供益处的治疗疾病和病况的方法，如细胞增殖性疾病、自身免疫或炎症性疾病、神经退行性疾病、病毒性疾病、疟疾或其组合。
• 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。