3α,16α,20(R),25-tetrahydroxy-2,11,22-trioxocucurbita-5,23(E)-diene | 68422-20-8

• 分子结构分类: 有机化合物 - 脂质和类脂质分子 - 类固醇和类固醇衍生物
• 英文名称: 3α,16α,20(R),25-tetrahydroxy-2,11,22-trioxocucurbita-5,23(E)-diene
• 英文别名: 3-epi-isocucurbitacin D；isocucurbitacin D；iso-cucurbitacin D；(3S,8S,9R,10R,13R,14S,16R,17R)-17-[(E,2R)-2,6-dihydroxy-6-methyl-3-oxohept-4-en-2-yl]-3,16-dihydroxy-4,4,9,13,14-pentamethyl-3,7,8,10,12,15,16,17-octahydro-1H-cyclopenta[a]phenanthrene-2,11-dione
• CAS: 68422-20-8
• 化学式: C₃₀H₄₄O₇
• 分子量: 516.675
• InChiKey: ALPSEMFPAVSKJO-DJMAWCNKSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.9
• 重原子数：
  37
• 可旋转键数：
  4
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.77
• 拓扑面积：
  132
• 氢给体数：
  4
• 氢受体数：
  7

反应信息

• 作为产物：
  描述：

  葫芦素 D 在 silica gel 作用下， 以 二氯甲烷 为溶剂， 反应 72.0h， 以25%的产率得到3α,16α,20(R),25-tetrahydroxy-2,11,22-trioxocucurbita-5,23(E)-diene
  参考文献：
  名称：

  Cucurbitacin D Is a Disruptor of the HSP90 Chaperone Machinery

  摘要：

  Heat shock protein 90 (Hsp90) facilitates the maturation of many newly synthesized and unfolded proteins (clients) via the Hsp90 chaperone cycle, in which Hsp90 forms a heteroprotein complex and relies upon cochaperones, immunophilins, etc., for assistance in client folding. Hsp90 inhibition has emerged as a strategy for anticancer therapies due to the involvement of clients in many oncogenic pathways. Inhibition of chaperone function results in client ubiquitinylation and degradation via the proteasome, ultimately leading to tumor digression. Small molecule inhibitors perturb ATPase activity at the N-terminus and include derivatives of the natural product geldanamycin. However, N-terminal inhibition also leads to induction of the pro-survival heat shock response (HSR), in which displacement of the Hsp90-bound transcription factor, heat shock factor-1, translocates to the nucleus and induces transcription of heat shock proteins, including Hsp90. An alternative strategy for Hsp90 inhibition is disruption of the Hsp90 heteroprotein complex. Disruption of the Hsp90 heteroprotein complex is an effective strategy to prevent client maturation without induction of the HSR. Cucurbitacin D, isolated from Cucurbita texana, and 3-epi-isocucurbitacin D prevented client maturation without induction of the HSR. Cucurbitacin D also disrupted interactions between Hsp90 and two cochaperones, Cdc37 and p23.

  DOI：

  10.1021/acs.jnatprod.5b00054

文献信息

• CHEMOSENSORY RECEPTOR LIGAND-BASED THERAPIES
  申请人：Anji Pharma (US) LLC

  公开号：EP2661266B1

  公开（公告）日：2020-09-16
• Chemosensory Receptor Ligand-Based Therapies
  申请人：BARON Alain D.

  公开号：US20120177730A1

  公开（公告）日：2012-07-12

  Provided herein are methods for treating conditions associated with a chemosensory receptor, including diabetes, obesity, and other metabolic diseases, disorders or conditions by administrating a composition comprising a chemosensory receptor ligand, such as a bitter receptor ligand. Also provided herein are chemosensory receptor ligand compositions, including bitter receptor ligand compositions, and methods for the preparation thereof for use in the methods of the present invention. Also provided herein are compositions comprising metformin and salts thereof and methods of use.
• US9050292B2
  申请人：——

  公开号：US9050292B2

  公开（公告）日：2015-06-09
• US9463170B2
  申请人：——

  公开号：US9463170B2

  公开（公告）日：2016-10-11
• US9962344B2
  申请人：——

  公开号：US9962344B2

  公开（公告）日：2018-05-08