5,21-Dichloro-3-[3,4-dihydroxy-6-(hydroxymethyl)-5-methoxyoxan-2-yl]-3,13,23-triazahexacyclo[14.7.0.02,10.04,9.011,15.017,22]tricosa-1,4(9),5,7,10,15,17(22),18,20-nonaene-12,14-dione | 93908-02-2

• 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
• 英文名称: 5,21-Dichloro-3-[3,4-dihydroxy-6-(hydroxymethyl)-5-methoxyoxan-2-yl]-3,13,23-triazahexacyclo[14.7.0.02,10.04,9.011,15.017,22]tricosa-1,4(9),5,7,10,15,17(22),18,20-nonaene-12,14-dione
• CAS: 93908-02-2
• 化学式: C₂₇H₂₁Cl₂N₃O₇
• 分子量: 570.4
• InChiKey: QEHOIJJIZXRMAN-UHFFFAOYSA-N

物化性质

• 溶解度：
  二甲基亚砜：≥3 mg/mL
• 稳定性/保质期：

  遵照规定使用和储存，则不会发生分解。

计算性质

• 辛醇/水分配系数(LogP)：
  2.6
• 重原子数：
  39
• 可旋转键数：
  3
• 环数：
  7.0
• sp3杂化的碳原子比例：
  0.26
• 拓扑面积：
  146
• 氢给体数：
  5
• 氢受体数：
  7

制备方法与用途

生物活性

Rebeccamycin 是一种由放线菌 Saccharotrix aerocolonigenes 产生的抗肿瘤抗生素，能抑制 DNA 拓扑异构酶 I (DNA topoisomerase I)。它主要通过毒害拓扑异构酶 I 发挥其抗肿瘤作用，对蛋白激酶 C 和拓扑异构酶 II 的影响较小。

靶点	传统细胞毒性剂
Topoisomerase I	Traditional Cytotoxic Agents

体外研究

Rebeccamycin 对多种人类肿瘤细胞系具有活性，包括 A549（肺腺癌）、HCT-116（结肠癌）和 KB（鼻咽癌）。此外，它还对某些革兰氏阳性细菌表现出抗菌活性，如金黄色葡萄球菌 (Staphylococcus aureus) 和粪链球菌 (Streptococcus faecalis)。

体内研究

Rebeccamycin 在 2-256 mg/kg 的剂量下（腹腔注射；连续9天）延长了 B16 黑色素瘤和 L1210 白血病小鼠的存活时间。

动物模型	CDF1 小鼠 (B16 黑色素瘤，L1210 白血病)
剂量	2, 4, 8, 16, 32, 64, 128, 256 mg/kg
给药方式	腹腔注射；连续9天
结果	在剂量水平从8到256 mg/kg 的小鼠存活时间延长。

文献信息

• Oligo-Aminosaccharide compound
  申请人：Wada Takeshi

  公开号：US20110003980A1

  公开（公告）日：2011-01-06

  An oligo-aminosaccharide compound formed by binding 3 to 6 saccharides, such as 2,6-diamino-2,6-dideoxy-α-(1→4)-D-glucopyranose oligomers, or a salt thereof, which has high affinity to a double-stranded nucleic acid.

  由3到6个糖苷结合形成的寡糖氨基酸化合物，例如2,6-二氨基-2,6-二去氧-α-(1→4)-D-葡萄糖吡喃糖寡聚体，或其盐，具有高亲和力双链核酸。
• Combination Therapy III
  申请人：TURUN YLIOPISTO

  公开号：US10166241B2

  公开（公告）日：2019-01-01

  The invention is based on a finding that silencing HDAC4gene sensitizes cancer cells for apoptosis-inducing activity of certain small molecule chemotherapeutic agents. Thus, the invention is directed to a respective combination therapy, sensitization method and pharmaceutical compositions.

  本发明基于一项发现，即沉默 HDAC4 基因可使癌细胞对某些小分子化疗药物的凋亡诱导活性敏感。因此，本发明涉及一种相应的联合疗法、增敏方法和药物组合物。
• COMBINATION THERAPY
  申请人：Westermarck Jukka

  公开号：US20140135377A1

  公开（公告）日：2014-05-15

  The invention is based on a finding that silencing PME-1 gene sensitizes cancer cells for apoptosis-inducing activity of certain small molecule chemotherapeutic agents. Thus, the invention is directed to a respective combination therapy, sensitization method and pharmaceutical compositions.
• COMBINATION THERAPY III
  申请人：TURUN YLIOPISTO

  公开号：US20150209369A1

  公开（公告）日：2015-07-30

  The invention is based on a finding that silencing HDAC4gene sensitizes cancer cells for apoptosis-inducing activity of certain small molecule chemotherapeutic agents. Thus, the invention is directed to a respective combination therapy, sensitization method and pharmaceutical compositions.
• USE OF MALEIMIDE DERIVATIVES FOR PREVENTING AND TREATING CANCER
  申请人：CENTOGENE AG

  公开号：US20150313882A1

  公开（公告）日：2015-11-05

  The present invention is related to a compound of formula (I) a pharmaceutically acceptable salt thereof, a hydrate thereof, a solvate thereof, a metabolite thereof or a prodrug thereof; for use in a method for the treatment and/or prevention of cancer, wherein X is selected from the group consisting of N—R 1 , O and S; R1 is selected from the group consisting of alkyl, cycloalkyl, aryl, arylalkyl and hydrogen; R 2 is selected from the group consisting of indolyl, substituted indolyl, azaindolyl and substituted azaindolyl; and R 3 is selected from the group consisting of aryl, substituted aryl, unsubstituted heteroaryl, heterocyclyl and substituted heterocyclyl.