incednine | 869768-51-4

• 分子结构分类: 有机化合物 - 有机氧化合物
• 英文名称: incednine
• 英文别名: (3Z,5E,7E,9E,11R,12S,13Z,15E,17E,19E,21E,24S)-11-hydroxy-12-[(2S,3R,4R,5R)-4-hydroxy-3-(methylamino)-5-[(2S,5S,6R)-6-methyl-5-(methylamino)oxan-2-yl]oxyoxan-2-yl]oxy-3-methoxy-5,11,17,21,24-pentamethyl-1-azacyclotetracosa-3,5,7,9,13,15,17,19,21-nonaen-2-one
• CAS: 869768-51-4
• 化学式: C₄₂H₆₃N₃O₈
• 分子量: 737.978
• InChiKey: VTEKRFJHUHAGJO-WNETYGQVSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  5.2
• 重原子数：
  53
• 可旋转键数：
  7
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.55
• 拓扑面积：
  140
• 氢给体数：
  5
• 氢受体数：
  10

反应信息

• 作为反应物：
  描述：

  incednine 、 4-溴苯甲酰氯 在 吡啶 作用下， 反应 16.0h， 生成 4''-N-4-bromobenzoyl incednine
  参考文献：
  名称：

  Discovery of Incednine as a Potent Modulator of the Anti-apoptotic Function of Bcl-xL from Microbial Origin

  摘要：

  Anti-apoptotic oncoproteins Bcl-2 and BcI-xL are overexpressed in many cancers and play a crucial role in cancer initiation, progression, and resistance to chemotherapy. Therefore, the discovery of a functional inhibitor for these proteins and improved understanding of the molecular mechanisms of these proteins will be an aid to novel anti-tumor therapies. Here, using chemical-genetic cell-based screening, we have discovered a chemically and biologically unique substance, incednine, as a novel functional modulator of Bcl-2/Bcl-xL from the fermentation broth of Streptomyces sp. ML-693-90F3. This compound was isolated as a HCI salt by solvent extraction and using centrifugal liquid-liquid partition chromatography. Its structure was elucidated by spectroscopic analysis, X-ray crystallographic analysis, and computational studies. Incednine has a molecular formula, C42H63N3O8, and consists of a novel skeletal structure, enol-ether amide in a 24-membered macrolactam core, with two aminosugars. Bcl-xL-overexpressing Ms-1 cells displayed resistance to several anti-tumor agents; however, anti-tumor agent-induced cell death was observed only when cells were treated with incednine. Overexpression of BcI-xL inhibited cell death in Bax-overexpressing HEK293T cells by forming a complex with Bax, whereas Bcl-xL failed to inhibit cell death in the presence of incednine without affecting the heterodimerization of Bcl-xL and Bax. These findings suggest that incednine serves as a potent modulator of the anti-apoptotic Bcl-2/Bcl-xL distinct from the other known Bcl-2 inhibitors and could provide a chemical probe to study the underlying mechanisms of Bcl-2/Bcl-xL.

  DOI：

  10.1021/ja710124p