SGC0946抑制剂 | 1561178-17-3

• 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 - 有机氧化合物
• 中文名称: SGC0946抑制剂
• 中文别名: 1-(3-((((2R,3S,4R,5R)-5-(4-氨基-5-溴-7H-吡咯并[2,3-D]嘧啶-7-基)-3,4-二羟基四氢呋喃-2-基)甲基)(异丙基)氨基)丙基)-3-(4-(叔丁基)苯基)脲；1-[3-[[[((2R，3S，4R，5R)-5-](4-氨基-5-溴-7H-吡咯并[2,3-d]嘧啶-7-基)-3,4-二羟基四氢呋喃-2-基]甲基](异丙基)氨基]丙基]-3-[4-(2,2-二甲基乙基)苯基]脲；化合物SGC0946；组蛋白甲基转移酶DOT1L抑制剂；SGC946
• 英文名称: Sgc0946
• 英文别名: 1-[3-[[(2R,3S,4R,5R)-5-(4-amino-5-bromopyrrolo[2,3-d]pyrimidin-7-yl)-3,4-dihydroxyoxolan-2-yl]methyl-propan-2-ylamino]propyl]-3-(4-tert-butylphenyl)urea
• CAS: 1561178-17-3
• 化学式: C₂₈H₄₀BrN₇O₄
• 分子量: 618.6
• InChiKey: IQCKJUKAQJINMK-HUBRGWSESA-N

物化性质

• 熔点：
  125-126o C
• 沸点：
  771.5±60.0 °C(Predicted)
• 密度：
  1.48±0.1 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)：
  3
• 重原子数：
  40
• 可旋转键数：
  10
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.54
• 拓扑面积：
  151
• 氢给体数：
  5
• 氢受体数：
  8

安全信息

• 危险品标志：
  T
• 安全说明：
  S45
• 危险类别码：
  R25
• WGK Germany：
  3
• 包装等级：
  III
• 危险类别：
  6.1
• 危险性防范说明：
  P301+P310
• 危险品运输编号：
  2811
• 危险性描述：
  H301

制备方法与用途

生物活性

SGC 0946是一种高效的、选择性的DOT1L甲基转移酶抑制剂，在无细胞试验中IC50为0.3 nM，对一系列其他组蛋白甲基转移酶/HMTs（包括12 PMTs和DNMT1）没有活性。

体外研究

SGC 0946比其他组蛋白甲基转移酶/HMTs选择性高100倍。在A431细胞和MCF10A 细胞中，SGC 0946能够有效降低H3K79二甲基化，其IC50分别为2.6 nM 和8.8 nM，并且能够有效并选择性地杀死含MLL易位的细胞。与EPZ004777相比，SGC 0946更有效，适合作为研究DOT1L及DOT1L抑制剂用于癌症治疗的化学探针。

特征

Cell-active DOT1L-selective chemical probe.

Target	Value
DOT1L (Cell-free assay)	0.3 nM

文献信息

• NOVEL FUSION MOLECULES AND USES THEREOF
  申请人：FOUNDATION MEDICINE, INC.

  公开号：US20160009785A1

  公开（公告）日：2016-01-14

  Novel fusion molecules and uses are disclosed.
• COMBINATIONS OF LSD1 INHIBITORS FOR THE TREATMENT OF HEMATOLOGICAL MALIGNANCIES
  申请人：HOFFMANN-LA ROCHE INC.

  公开号：US20170281566A1

  公开（公告）日：2017-10-05

  The instant invention relates to combinations of the compound of formula (I) or pharmaceutically acceptable salts thereof with other active pharmaceutical ingredients pharmaceutical compositions comprising them, and their use as medicaments, particularly for the treatment of hematological malignancies.
• COMBINATIONS OF LSD1 INHIBITORS FOR USE IN THE TREATMENT OF SOLID TUMORS
  申请人：HOFFMANN-LA ROCHE INC.

  公开号：US20170281567A1

  公开（公告）日：2017-10-05

  The instant invention relates to therapeutic combinations of LSD1 inhibitors and one or more other active pharmaceutical ingredient(s) or pharmaceutically acceptable salts thereof. The combinations are particularly useful for treating neoplastic diseases, such as cancer, particularly small cell lung cancer (SCLC).
• 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.
• METHOD FOR PREPARING INDUCED MESENCHYMAL STEM CELLS AND IMPROVING MESENCHYMAL STEM CELL'S CHARACTERS AND ITS APPLICATIONS
  申请人：ACADEMIA SINICA

  公开号：US20180055887A1

  公开（公告）日：2018-03-01

  The present invention generally relates to a method for preparing induced mesenchymal stem cells (iMSCs) and its applications. The iMSCs, like MSCs, can differentiate into multiple lineages, which may be beneficial for disease treatments. In addition, the present invention also provides a method for improving the MSC's functional characteristics such that the MSCs are more suitable for cell therapy or in vitro applications.