EPZ 011989 | 1598383-40-4

• 物质功能分类: 生物化工 - 生化试剂 - 激动剂抑制剂
• 分子结构分类: 有机化合物 - 苯类化合物 - 苯和取代衍生物
• 英文名称: EPZ 011989
• 英文别名: N-((4,6-dimethyl-2-oxo-1,2-dihydropyridin-3-yl)methyl)-3-(ethyl((trans)-4-((2-methoxyethyl)(methyl)amino)cyclohexyl)amino)-2-methyl-5-(3-morpholinoprop-1-yn-1-yl)benzamide；N-((4,6-dimethyl-2-oxo-1,2-dihydropyridin-3-yl)methyl)-3-(ethyl(trans)-(4-((2-methoxyethyl)(methyl)amino)cyclohexyl)amino)-2-methyl-5-(3-morpholinoprop-1-yn-1-yl)benzamide；EPZ011989
• CAS: 1598383-40-4
• 化学式: C₃₅H₅₁N₅O₄
• 分子量: 605.821
• InChiKey: XQFINGFCBFHOPE-WXUXXXNLSA-N

物化性质

• 沸点：
  756.7±60.0 °C(Predicted)
• 密度：
  1.17±0.1 g/cm3(Predicted)
• 溶解度：
  DMSO:55.0(最大浓度 mg/mL);90.79(最大浓度 mM)DMF:10.0(最大浓度 mg/mL);16.51(最大浓度 mM)乙醇:60.0(最大浓度 mg/mL);99.04(最大浓度 mM)乙醇:PBS (pH 7.2) (1:1):0.5(最大浓度 mg/mL);0.83(最大浓度 mM)

计算性质

• 辛醇/水分配系数(LogP)：
  3.63
• 重原子数：
  44.0
• 可旋转键数：
  11.0
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.6
• 拓扑面积：
  90.14
• 氢给体数：
  2.0
• 氢受体数：
  7.0

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

• 作为产物：
  描述：

  4-N-Boc-氨基环己酮 在 盐酸 、 copper(l) iodide 、 四(三苯基膦)钯 、 potassium carbonate 、 溶剂黄146 、 三乙胺 、 potassium iodide 、 sodium hydroxide 作用下， 以 甲醇 、 乙醇 、 二氯甲烷 、 水 、 二甲基亚砜 、 N,N-二甲基甲酰胺 、 乙腈 为溶剂， 反应 56.24h， 生成 EPZ 011989
  参考文献：
  名称：

  EPZ011989, A Potent, Orally-Available EZH2 Inhibitor with Robust in Vivo Activity

  摘要：

  Inhibitors of the protein methyltransferase Enhancer of Zeste Homolog 2 (EZH2) may have significant therapeutic potential for the treatment of B cell lymphomas and other cancer indications. The ability of the scientific community to explore fully the spectrum of EZH2-associated pathobiology has been hampered by the lack of in vivo-active tool compounds for this enzyme. Here we report the discovery and characterization of EPZ011989, a potent, selective, orally bioavailable inhibitor of EZH2 with useful pharmacokinetic properties. EPZ011989 demonstrates significant tumor growth inhibition in a mouse xenograft model of human B cell lymphoma. Hence, this compound represents a powerful tool for the expanded exploration of EZH2 activity in biology.

  DOI：

  10.1021/acsmedchemlett.5b00037

文献信息

• [EN] COMPOSITIONS AND METHODS FOR TREATING EZH2-MEDIATED CANCER<br/>[FR] COMPOSITIONS ET PROCÉDÉS POUR LE TRAITEMENT DU CANCER À MÉDIATION PAR L'EZH2
  申请人：ICAHN SCHOOL MED MOUNT SINAI

  公开号：WO2018081530A1

  公开（公告）日：2018-05-03

  Methods for designing bivalent compounds which selectively degrade/disrupt EZH2 and compositions and methods of using such degraders/disruptors to treat EZH2-mediated cancer are provided.

  提供的设计二价化合物的方法，这些化合物可选择性地降解/破坏EZH2，以及使用这种降解剂/破坏剂治疗EZH2介导的癌症的组合物和方法。
• Substituted Benzene Compounds
  申请人：Epizyme, Inc.

  公开号：US20140107122A1

  公开（公告）日：2014-04-17

  The present invention relates to substituted benzene compounds. The present invention also relates to pharmaceutical compositions containing these compounds and methods of treating cancer by administering these compounds and pharmaceutical compositions to subjects in need thereof. The present invention also relates to the use of such compounds for research or other non-therapeutic purposes.

  本发明涉及取代苯化合物。本发明还涉及含有这些化合物的药物组合物以及通过向需要的受试者投予这些化合物和药物组合物来治疗癌症的方法。本发明还涉及将这些化合物用于研究或其他非治疗目的的用途。
• SUBSTITUTED BENZENE COMPOUNDS
  申请人：EPIZYME, INC.

  公开号：US20150174136A1

  公开（公告）日：2015-06-25

  The present invention relates to substituted benzene compounds. The present invention also relates to pharmaceutical compositions containing these compounds and methods of treating cancer by administering these compounds and pharmaceutical compositions to subjects in need thereof. The present invention also relates to the use of such compounds for research or other non-therapeutic purposes.

  本发明涉及取代苯基化合物。本发明还涉及含有这些化合物的药物组合物以及通过向需要治疗的受试者施用这些化合物和药物组合物来治疗癌症的方法。本发明还涉及将这些化合物用于研究或其他非治疗目的的用途。
• Substituted benzene compounds
  申请人：Epizyme, Inc.

  公开号：US10092572B2

  公开（公告）日：2018-10-09

  The present invention relates to substituted benzene compounds. The present invention also relates to pharmaceutical compositions containing these compounds and methods of treating cancer by administering these compounds and pharmaceutical compositions to subjects in need thereof. The present invention also relates to the use of such compounds for research or other non-therapeutic purposes.

  本发明涉及取代苯化合物。本发明还涉及含有这些化合物的药物组合物，以及通过向有需要的受试者施用这些化合物和药物组合物来治疗癌症的方法。本发明还涉及将这些化合物用于研究或其它非治疗目的。
• Methods of treating cancers overexpressing CARM1 with EZH2 inhibitors and platinum-based antineoplastic drugs
  申请人：The Wistar Institute of Anatomy and Biology

  公开号：US10987353B2

  公开（公告）日：2021-04-27

  In some embodiments, therapeutic treatments for a disease such as a cancer are disclosed, including pharmaceutical compositions and methods of using pharmaceutical compositions for treating the cancer wherein the cancer cells overexpress arginine methyltransferase CARM1. In some embodiments, the therapeutic treatments disclosed include methods comprising the step of administering a therapeutically effective dose of an enhancer of zeste homolog 2 (EZH2) inhibitor to a subject, including a human subject, wherein the cancer cells of the subject overexpress arginine methyltransferase CARM1. In some embodiments, the EZH2 inhibitors are administered in conjunction with platinum-based antineoplastic drugs.

  在一些实施方案中，公开了癌症等疾病的治疗方法，包括药物组合物和使用药物组合物治疗癌症的方法，其中癌细胞过度表达精氨酸甲基转移酶CARM1。在一些实施方案中，所公开的治疗方法包括向受试者（包括人类受试者）施用治疗有效剂量的泽斯特同源增强子2（EZH2）抑制剂的步骤，其中受试者的癌细胞过度表达精氨酸甲基转移酶CARM1。 在一些实施方案中，EZH2抑制剂与铂类抗肿瘤药物联合施用。