(8E,12E,24E)-19,29-Bis-(3,4-dicarboxy-butyryloxy)-4-ethyl-15-hydroxy-2,8,10,12,14,16,26-heptamethyl-5-oxo-triaconta-8,12,24-trienoic acid

• 分子结构分类: 有机化合物 - 脂质和类脂质分子 - 异戊烯醇脂质
• 英文名称: (8E,12E,24E)-19,29-Bis-(3,4-dicarboxy-butyryloxy)-4-ethyl-15-hydroxy-2,8,10,12,14,16,26-heptamethyl-5-oxo-triaconta-8,12,24-trienoic acid
• 英文别名: 2-[2-[(6E,18E,22E)-29-carboxy-12-(3,4-dicarboxybutanoyloxy)-27-ethyl-16-hydroxy-5,15,17,19,21,23-hexamethyl-26-oxotriaconta-6,18,22-trien-2-yl]oxy-2-oxoethyl]butanedioic acid
• 化学式: C₅₁H₈₂O₁₆
• 分子量: 951.202
• InChiKey: HPLVKFZNICIAKY-MBJHXXLGSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  8.2
• 重原子数：
  67
• 可旋转键数：
  40
• 环数：
  0.0
• sp3杂化的碳原子比例：
  0.73
• 拓扑面积：
  276
• 氢给体数：
  6
• 氢受体数：
  16

反应信息

• 作为反应物：
  描述：

  重氮甲烷 、 (8E,12E,24E)-19,29-Bis-(3,4-dicarboxy-butyryloxy)-4-ethyl-15-hydroxy-2,8,10,12,14,16,26-heptamethyl-5-oxo-triaconta-8,12,24-trienoic acid 以 甲醇 、 乙醚 、 二氯甲烷 为溶剂， 反应 4.0h， 生成 3-Methoxycarbonyl-pentanedioic acid (7E,11E)-1-[(E)-10-(3,4-bis-methoxycarbonyl-butyryloxy)-7-methyl-undec-5-enyl]-16-ethyl-5-hydroxy-18-methoxycarbonyl-4,6,8,10,12-pentamethyl-15-oxo-nonadeca-7,11-dienyl ester methyl ester
  参考文献：
  名称：

  Structure, Chemistry, and Biology of Actinoplanic Acids: Potent Inhibitors of Ras Farnesyl-Protein Transferase

  摘要：

  The ras oncogene is found mutated in 50% of colon and 90% of pancreatic carcinomas. Farnesyl-protein transferase (FPTase) catalyzes farnesylation of the Ras protein, which is the essential step for the association of Ras with the plasma membrane, a critical requirement for Ras-mediated cell-transforming activity. Continued search for FPTase inhibitors led to the discovery of actinoplanic acid A and B, novel and potent inhibitors of the enzyme. We report here the details of the isolation, structure elucidation, chemistry, and biological activity of actinoplanic acid A and a significantly more active congener, actinoplanic acid B. Both of these compounds are highly functionalized 30-carbon chain length polyketides terminating with a carboxylic acid group. They are esterified with two units of carballylic acid. Actinoplanic acid A is cyclized into a macrocyclic bis-lactone, while the more potent acid B is acyclic. Both acids A and B inhibit farnesyl-protein transferase (FPTase) with IC50's of 230 and 50 nM and K-i values of 98 and 8 nM, respectively. The inhibition of FPTase by acids A and B is competitive with respect to farnesyl pyrophosphate (FPP) and uncompetitive with respect to Ras-CVIM, the peptide substrate.

  DOI：

  10.1021/jo00129a033

文献信息

• Processes and host cells for genome, pathway, and biomolecular engineering
  申请人：enEvolv, Inc.

  公开号：US10370654B2

  公开（公告）日：2019-08-06

  The present disclosure provides compositions and methods for genomic engineering.

  本公开提供了基因组工程的组合物和方法。
• PROCESSES AND HOST CELLS FOR GENOME, PATHWAY, AND BIOMOLECULAR ENGINEERING
  申请人：enEvolv, Inc.

  公开号：EP3027754A1

  公开（公告）日：2016-06-08
• INHIBITION OF ISOPRENOID BIOSYNTHETIC PATHWAYS TO TREAT NEUROINFLAMMATORY DISORDERS
  申请人：TABACZYNSKI David A.

  公开号：US20160303146A1

  公开（公告）日：2016-10-20

  This invention provides methods and pharmaceutical compositions that can treat neuroinflammatory disease by reducing the production of pyrophosphate intermediates produced during the biosynthesis of isoprenoids. The pyrophosphate compounds being inhibited are normally produced through the mevalonate and non-mevalonate pathways of the host vertebrate organisms and their symbiotic and pathogenic microorganisms. The methods involve administering to a patient an inhibitor of the mevalonate-dependent pathway, an inhibitor of the non-mevalonate pathway, or combination of such inhibitors.
• INHIBITION OF ISOPRENOID BIOSYNTHETIC PATHWAYS TO TREAT AUTOIMMUNE DISORDERS
  申请人：TABACZYNSKI David A.

  公开号：US20160375041A1

  公开（公告）日：2016-12-29

  The invention provides methods and pharmaceutical compositions that can treat autoimmune disease by reducing the production of pyrophosphate intermediates produced during the biosynthesis of isoprenoids. The pyrophosphate compounds being inhibited are normally produced through the mevalonate and non-mevalonate pathways of the host vertebrate organisms and their symbiotic and pathogenic microorganisms. The methods involve administering to a patient an inhibitor of the mevalonate-dependent pathway, an inhibitor of the non-mevalonate pathway, or combination of such inhibitors.
• US5510371A
  申请人：——

  公开号：US5510371A

  公开（公告）日：1996-04-23