N-[[6-(羟基氨基)-6-氧代己基]氧基]-3,5-二甲基-苯甲酰胺 | 1418033-25-6

• 物质功能分类: 生物化工 - 抑制剂 - 表观遗传学(Epigenetics)
• 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: N-[[6-(羟基氨基)-6-氧代己基]氧基]-3,5-二甲基-苯甲酰胺
• 英文名称: LMK235
• 英文别名: N-((6 (hydroxyamino)-6-oxohexyl)oxy)-3,5-dimethylbenzamide；N-((6-(hydroxyamino)-6-oxohexyl)oxy)-3,5-dimethylbenzamide；N-[6-(hydroxyamino)-6-oxohexoxy]-3,5-dimethylbenzamide
• CAS: 1418033-25-6
• 化学式: C₁₅H₂₂N₂O₄
• 分子量: 294.351
• InChiKey: VRYZCEONIWEUAV-UHFFFAOYSA-N

物化性质

• 熔点：
  135-138°C
• 密度：
  1.155±0.06 g/cm3(Predicted)
• 溶解度：
  在DMSO中的溶解度为20mg/mL，澄清

计算性质

• 辛醇/水分配系数(LogP)：
  1.8
• 重原子数：
  21
• 可旋转键数：
  8
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.47
• 拓扑面积：
  87.7
• 氢给体数：
  3
• 氢受体数：
  4

安全信息

• 危险品标志：
  Xn
• 危险类别码：
  R22
• WGK Germany：
  3
• 危险性防范说明：
  P280,P305+P351+P338
• 危险性描述：
  H302

反应信息

• 作为产物：
  描述：

  6-(aminooxy)-N-(benzyloxy)hexanamide 在 4-二甲氨基吡啶 、 palladium 10% on activated carbon 、 氢气 、 1,2-二氯乙烷 作用下， 以 四氢呋喃 、 二氯甲烷 为溶剂， 20.0 ℃ 、100.0 kPa 条件下， 反应 28.0h， 生成 N-[[6-(羟基氨基)-6-氧代己基]氧基]-3,5-二甲基-苯甲酰胺
  参考文献：
  名称：

  Histone Deacetylase (HDAC) Inhibitors with a Novel Connecting Unit Linker Region Reveal a Selectivity Profile for HDAC4 and HDAC5 with Improved Activity against Chemoresistant Cancer Cells

  摘要：

  The synthesis and biological evaluation of new potent hydroxamate-based HDAC inhibitors with a novel alkoxyamide connecting unit linker region are described. Biological evaluation includes MTT and cellular HDAC assays on sensitive and chemoresistant cancer cell lines as well as HDAC profiling of selected compounds. Compound 191 (LMK235) (N-((6-(hydroxyamino)-6-oxohexyl)oxy)-3,5-dimethylbenzamide) showed similar effects compared to vorinostat on inhibition of cellular HDACs in a pan-HDAC assay but enhanced cytotoxic effects against the human cancer cell lines A2780, Cal27, Kyse510, and MDA-MB231. Subsequent HDAC profiling yielded a novel HDAC isoform selectivity profile of 19i in comparison to vorinostat or trichostatin A (TSA). 19i shows nanomolar inhibition of HDAC4 and HDAC5, whereas vorinostat and TSA inhibit HDAC4 and HDAC5 in the higher micromolar range.

  DOI：

  10.1021/jm301254q

文献信息

• Methods for production of functional beta cells
  申请人：Janssen Biotech, Inc.

  公开号：US10633635B2

  公开（公告）日：2020-04-28

  The invention provides for methods of differentiating pancreatic endocrine cells into pancreatic beta cells expressing PDX1, NKX6.1, MAFA, UCN3 and SLC2A. These pancreatic beta cells may be obtained by step-wise differentiation of pluripotent stem cells. The pancreatic beta cells exhibit glucose-dependent mitochondrial respiration and glucose-stimulated insulin secretion similar to islet cells.

  本发明提供了将胰腺内分泌细胞分化成表达PDX1、NKX6.1、MAFA、UCN3和SLC2A的胰腺β细胞的方法。这些胰腺β细胞可通过多能干细胞的逐步分化获得。胰岛β细胞表现出与胰岛细胞相似的葡萄糖依赖性线粒体呼吸和葡萄糖刺激的胰岛素分泌。
• EXPANSION AND DIFFERENTIATION OF INNER EAR SUPPORTING CELLS AND METHODS OF USE THEREOF
  申请人：Massachusetts Eye & Ear Infirmary

  公开号：EP3407901B1

  公开（公告）日：2021-07-21
• CLASS IIA HDAC INHIBITORS FOR THE TREATMENT OF INFECTION
  申请人：RESEARCH DEVELOPMENT FOUNDATION

  公开号：US20150290168A1

  公开（公告）日：2015-10-15

  In some aspects, methods for treating a bacterial infection in a mammalian subject are provided. In some embodiments, a class IIa HDAC inhibitor such as, e.g., a HDAC4 inhibitor, may be used to treat a bacterial infection such as, e.g., anthrax, pertussis, tuberculosis, or cholera.
• GENERATION OF HUMAN PLURIPOTENT STEM CELL DERIVED FUNCTIONAL BETA CELLS SHOWING A GLUCOSE-DEPENDENT MITOCHONDRIAL RESPIRATION AND TWO-PHASE INSULIN SECRETION RESPONSE
  申请人：Janssen Biotech, Inc.

  公开号：US20170362572A1

  公开（公告）日：2017-12-21

  The invention provides for methods of differentiating pancreatic endocrine cells into pancreatic beta cells expressing PDX1, NKX6.1, MAFA, UCN3 and SLC2A. These pancreatic beta cells may be obtained by step-wise differentiation of pluripotent stem cells. The pancreatic beta cells exhibit glucose-dependent mitochondrial respiration and glucose-stimulated insulin secretion similar to islet cells.
• US9693994B2
  申请人：——

  公开号：US9693994B2

  公开（公告）日：2017-07-04