(4S)-MeHex-D-Val-Thr-Val-D-Val-D-Pro-Orn-D-allo-Ile-cyclo(D-allo-Thr-D-allo-Ile-D-Val-Phe-Z-Dhb-Val) | 681272-30-0

• 分子结构分类: 有机化合物 - 有机酸及其衍生物 - 肽模拟物
• 英文名称: (4S)-MeHex-D-Val-Thr-Val-D-Val-D-Pro-Orn-D-allo-Ile-cyclo(D-allo-Thr-D-allo-Ile-D-Val-Phe-Z-Dhb-Val)
• 英文别名: (4S)-methylhexanoic kahalalide F；isokahalalide F；isoKF；Elisidepsin；(2R)-N-[(2S)-5-amino-1-[[(2R,3S)-1-[[(3S,6Z,9S,12R,15R,18R,19R)-9-benzyl-15-[(2S)-butan-2-yl]-6-ethylidene-19-methyl-2,5,8,11,14,17-hexaoxo-3,12-di(propan-2-yl)-1-oxa-4,7,10,13,16-pentazacyclononadec-18-yl]amino]-3-methyl-1-oxopentan-2-yl]amino]-1-oxopentan-2-yl]-1-[(2R)-2-[[(2S)-2-[[(2S,3R)-3-hydroxy-2-[[(2R)-3-methyl-2-[[(4S)-4-methylhexanoyl]amino]butanoyl]amino]butanoyl]amino]-3-methylbutanoyl]amino]-3-methylbutanoyl]pyrrolidine-2-carboxamide
• CAS: 681272-30-0
• 化学式: C₇₅H₁₂₄N₁₄O₁₆
• 分子量: 1477.89
• InChiKey: ZNVCPJPCKSJWDH-UCTDCHLSSA-N

物化性质

• 沸点：
  1630.2±65.0 °C(Predicted)
• 密度：
  1.20±0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  7.4
• 重原子数：
  105
• 可旋转键数：
  33
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.71
• 拓扑面积：
  442
• 氢给体数：
  14
• 氢受体数：
  17

制备方法与用途

elisidepsin（PM02734）是一种具有抗肿瘤活性的环状脱肽，能够抑制癌细胞增殖，并可应用于癌症研究，尤其在非小细胞肺癌（NSCLC）的研究中发挥重要作用。[1][2][3][4]

反应信息

• 作为产物：
  描述：

  (4S)-MeHex-D-Val-Thr(tBu)-Val-D-Val-D-Pro-Orn(Boc)-D-allo-Ile-cyclo(D-allo-Thr-D-allo-Ile-D-Val-Phe-Z-Dhb-Val) 在 三氟乙酸 作用下， 以 水 为溶剂， 反应 1.0h， 以192 mg的产率得到(4S)-MeHex-D-Val-Thr-Val-D-Val-D-Pro-Orn-D-allo-Ile-cyclo(D-allo-Thr-D-allo-Ile-D-Val-Phe-Z-Dhb-Val)
  参考文献：
  名称：

  Kahalalide F合成类似物的构效关系。

  摘要：

  Kahalalide F（KF）是目前处于II期临床试验的天然产物。在这里，我们报告了132种新的Kahalalide F的类似物的固相合成及其在多达14种癌细胞系中的体外活性。这些类似物的结构-活性关系表明，KF对骨架立体定位修饰高度敏感，但对侧链大小修饰不敏感。这些观察结果表明该化合物具有确定的构象结构，并且还通过其主链而不是通过其侧链与手性化合物相互作用。在膜状环境中，N-末端脂族酸似乎是疏水浮标。此外，实现了体外活性的显着改善。

  DOI：

  10.1021/jm8000828

文献信息

• Combination therapy with an antitumor alkaloid
  申请人：Pharma Mar S.A.

  公开号：EP2786754A2

  公开（公告）日：2014-10-08

  The present invention relates to the combination of PM01183 with several anticancer drugs, in particular other anticancer drugs selected from antitumor platinum coordination complexes, antimetabolites, mitotic inhibitors, anticancer antibiotics, topoisomerase I and/or II inhibitors, proteasome inhibitors, histone deacetylase inhibitors, nitrogen mustard alkylating agents, nitrosourea alkylating agents, nonclassical alkylating agents, estrogen antagonists, androgen antagonists, mTOR inhibitors, tyrosine kinase inhibitors, and other agents selected from aplidine, ET-743, PM02734 and PM001 04, and the use of these combinations in the treatment of cancer.

  本发明涉及PM01183与多种抗癌药物的组合，特别是选自抗肿瘤铂配位络合物、抗代谢物、有丝分裂抑制剂、抗癌抗生素、拓扑异构酶I和/或II抑制剂、蛋白酶体抑制剂、组蛋白去乙酰化酶抑制剂的其他抗癌药物、氮芥烷化剂、亚硝基脲烷化剂、非经典烷化剂、雌激素拮抗剂、雄激素拮抗剂、mTOR 抑制剂、酪氨酸激酶抑制剂，以及选自 aplidine、ET-743、PM02734 和 PM001 04 的其他制剂，以及这些组合在癌症治疗中的应用。
• Antitumoral Treatments
  申请人：Pérez-Soler Román

  公开号：US20100226919A1

  公开（公告）日：2010-09-09

  The present invention relates to combinations of PM02734 with EGFR tyrosine kinase inhibitors, and the use of these combinations in the treatment of cancer.
• ANTITUMORAL TREATMENTS
  申请人：Hosta Leticia

  公开号：US20100323021A1

  公开（公告）日：2010-12-23

  The present invention relates to colloidal metal nanoparticles conjugated with Kahalalide F, or an analogue thereof, and their use in the treatment of cancer. The invention also relates to a method for increasing the antitumoral activity of Kahalalide F, or an analogue thereof, which comprises conjugating the Kahalalide F, on an analogue thereof, with a colloidal metal nanoparticle.
• Combination Therapy with an Antitumor Alkaloid
  申请人：Moneo Ocaña Victoria

  公开号：US20130266666A1

  公开（公告）日：2013-10-10

  The present invention relates to the combination of PM01183 with several anticancer drugs, in particular other anticancer drugs selected from antitumor platinum coordination complexes, antimetabolites, mitotic inhibitors, anticancer antibiotics, topoisomerase I and/or II inhibitors, proteasome inhibitors, histone deacetylase inhibitors, nitrogen mustard alkylating agents, nitrosourea alkylating agents, nonclassical alkylating agents, estrogen antagonists, androgen antagonists, mTOR inhibitors, tyrosine kinase inhibitors, and other agents selected from aplidine, ET-743, PM02734 and PM00104, and the use of these combinations in the treatment of cancer.
• COMBINATION THERAPY WITH AN ANTITUMOR ALKALOID
  申请人：PHARMA MAR, S.A.

  公开号：US20180078550A1

  公开（公告）日：2018-03-22

  The present invention relates to the combination of PM01183 with several anticancer drugs, in particular other anticancer drugs selected from antitumor platinum coordination complexes, antimetabolites, mitotic inhibitors, anticancer antibiotics, topoisomerase I and/or II inhibitors, proteasome inhibitors, histone deacetylase inhibitors, nitrogen mustard alkylating agents, nitrosourea alkylating agents, nonclassical alkylating agents, estrogen antagonists, androgen antagonists, mTOR inhibitors, tyrosine kinase inhibitors, and other agents selected from aplidine, ET-743, PM02734 and PM00104, and the use of these combinations in the treatment of cancer.