2(1H)-Pyrimidinone, 1-beta-D-ribofuranosyl- | 3690-10-6

• 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 - 核苷、核苷酸和类似物 - 嘧啶核苷
• 英文名称: 2(1H)-Pyrimidinone, 1-beta-D-ribofuranosyl-
• 英文别名: 1-[(2R,4R,5R)-3,4-dihydroxy-5-(hydroxymethyl)oxolan-2-yl]pyrimidin-2-one
• CAS: 3690-10-6
• 化学式: C₉H₁₂N₂O₅
• 分子量: 228.2
• InChiKey: RPQZTTQVRYEKCR-JJFBUQMESA-N

物化性质

• 熔点：
  160-162?C
• 沸点：
  499.0±55.0 °C(Predicted)
• 密度：
  1.73±0.1 g/cm3(Predicted)
• 溶解度：
  DMSO：16 mg/mL，可溶

计算性质

• 辛醇/水分配系数(LogP)：
  -1.5
• 重原子数：
  16
• 可旋转键数：
  2
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.56
• 拓扑面积：
  103
• 氢给体数：
  3
• 氢受体数：
  5

安全信息

• WGK Germany：
  3
• 危险性防范说明：
  P261,P305+P351+P338
• 危险性描述：
  H302,H315,H319

制备方法与用途

生物活性

Zebularine（NSC 309132，4-脱氧尿苷）是一种DNA甲基转移酶抑制剂，能够与DNA甲基转移酶形成共价复合物，并且还抑制胞苷脱氨酶。在无细胞试验中，其对胞苷脱氨酶的Ki值为2 μM。

靶点

Target	Value
DNA methyltransferase (无细胞试验)	-
Cytidine deaminase (无细胞试验)	2 μM (Ki)

体外研究

Zebularine 是一种胞苷类似物，含有2-(1H)-嘧啶酮环，最初合成用作胞苷脱氨酶抑制剂。它与细菌甲基转移酶形成紧密的共价复合物，并作用于N. crassa，通过抑制DNA甲基化来重新激活因甲基化而沉默的基因。Zebularine 不是选择性抑制剂，而是类似于5-Aza-CR的DNA甲基化抑制剂。在T24膀胱癌细胞中，它能够重新激活沉默的p16基因，并去甲基化其启动子区域。与正常成纤维细胞相比，Zebularine 更优先地掺入癌细胞系的DNA 中，显著抑制细胞生长和基因表达。此外，与正常成纤维细胞相比，Zebularine 还能够优先耗尽癌细胞中的DNA甲基转移酶1（DNMT1），并诱导癌症相关抗原基因的表达。

体内研究

处理携带肿瘤的小鼠时，Zebularine 表现出轻微的细胞毒性。以1000 mg/kg剂量给小鼠口服或腹腔注射后，平均最大体重变化为11%（95% CI = 4%-19%）。与对照组相比，高剂量 Zebularine 处理的小鼠肿瘤体积显著减小。

文献信息

• MUTUAL PRODRUG COMPRISING SHORT CHAIN FATTY ACIDS AND ZEBULARINE OR 1'-CYANO-CYTARABINE FOR CANCER TREATMENT
  申请人：KAINOS MEDICINE, INC.

  公开号：US20160228562A1

  公开（公告）日：2016-08-11

  The present invention provides mutual prodrugs comprising anti-cancer nucleosides and short chain fatty acids; methods for production of the mutual prodrugs; methods of treatment comprising administration of the mutual prodrugs; and pharmaceutical compositions comprising the mutual prodrugs. Further, the mutual prodrugs of the present invention can be used as therapeutic agents for the treatment of cancer diseases and conditions.

  本发明提供了包含抗癌核苷和短链脂肪酸的相互前药；制备相互前药的方法；通过给予相互前药进行治疗的方法；以及包含相互前药的制药组合物。此外，本发明的相互前药可用作治疗癌症疾病和病状的治疗剂。
• ORAL FORMULATIONS OF CYTIDINE ANALOGS AND METHODS OF USE THEREOF
  申请人：Etter Jeffrey B.

  公开号：US20090286752A1

  公开（公告）日：2009-11-19

  The present disclosure provides pharmaceutical compositions comprising cytidine analogs for oral administration, wherein the compositions release the cytidine analog substantially in the stomach. Also provided are methods of treating diseases and disorders using the oral formulations provided herein.
• METHODS FOR TREATING NON-SMALL CELL LUNG CANCER USING 5-AZACYTIDINE
  申请人：Nguyen Aaron N.

  公开号：US20110319355A1

  公开（公告）日：2011-12-29

  The present disclosure provides methods for treating subjects having non-small cell lung cancer, wherein the methods comprise administering to the subject a cytidine analog, such as 5-azacytidine. Also provided are methods relating to identification and treatment of particular non-small cell lung cancer types sensitive to particular cytidine analogs.
• METHODS FOR TREATING CANCERS USING ORAL FORMULATIONS OF CYTIDINE ANALOGS
  申请人：CELGENE CORPORATION

  公开号：US20150216886A1

  公开（公告）日：2015-08-06

  Provided herein are methods for treating subjects having a cancer, such as a relapsed or refractory solid tumor, wherein the method comprises administering to the subject a cytidine analog. In certain of the methods, the cytidine analog is administered alone or in combination with one or more anti-cancer agents. Also provided are methods for using a cytidine analog, to treat diseases and disorders including disorders related to abnormal cell proliferation, hematologic disorders, and immune disorders, among others. In certain of the methods, the cytidine analog is formulated in an oral dosage form and administered orally.
• ISOTOPOLOGUES OF 5-AZACYTIDINE
  申请人：Celgene Corporation

  公开号：US20180153916A1

  公开（公告）日：2018-06-07

  The present disclosure provides pharmaceutical compositions comprising cytidine analogs for oral administration, wherein the compositions release the cytidine analog substantially in the stomach. Also provided are methods of treating diseases and disorders using the oral formulations provided herein.