D-N^2'-deacetyl-N^2'-(3-mercapto-1-oxopropyl)maytansine

• 分子结构分类: 有机化合物 - 苯丙烷和聚酮 - 大环内酰胺类
• 英文名称: D-N^2'-deacetyl-N^2'-(3-mercapto-1-oxopropyl)maytansine
• 英文别名: [(1S,2R,3S,5S,6S,16E,18E,20R,21S)-11-chloro-21-hydroxy-12,20-dimethoxy-2,5,9,16-tetramethyl-8,23-dioxo-4,24-dioxa-9,22-diazatetracyclo[19.3.1.110,14.03,5]hexacosa-10,12,14(26),16,18-pentaen-6-yl] (2R)-2-[methyl(3-sulfanylpropanoyl)amino]propanoate
• 化学式: C₃₅H₄₈ClN₃O₁₀S
• 分子量: 738.299
• InChiKey: ANZJBCHSOXCCRQ-GPQZUGOWSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.2
• 重原子数：
  50
• 可旋转键数：
  8
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.6
• 拓扑面积：
  158
• 氢给体数：
  3
• 氢受体数：
  11

反应信息

• 作为产物：
  描述：

  (S)-2-(n-甲基-3-(甲基二磺酰基)丙酰胺)丙酸 在 乙二胺四乙酸 、 N,N'-二环己基碳二亚胺 、 zinc(II) chloride 、 1,4-二巯基-2,3-丁二醇 作用下， 以 甲醇 、 phosphate buffer 、 乙醚 、 二氯甲烷 、 乙酸乙酯 为溶剂， 反应 4.0h， 生成 D-N^2'-deacetyl-N^2'-(3-mercapto-1-oxopropyl)maytansine
  参考文献：
  名称：

  Semisynthetic Maytansine Analogues for the Targeted Treatment of Cancer

  摘要：

  Maytansine, a highly cytotoxic natural product, failed as an anticancer agent in human clinical trials because of unacceptable systemic toxicity. The potent cell killing ability of maytansine can be used in a targeted delivery approach for the selective destruction of cancer cells. A series of new maytansinoids, bearing a disulfide or thiol substituent were synthesized. The chain length of the ester side chain and the degree of steric hindrance on the carbon atom bearing the thiol substituent were varied. Several of these maytansinoids were found to be even more potent in vitro than maytansine. The targeted delivery of these maytansinoids, using monoclonal antibodies, resulted in a high, specific killing of the targeted cells in vitro and remarkable antitumor activity in vivo.

  DOI：

  10.1021/jm060319f

文献信息

• Biological materials and uses thereof
  申请人：Antikor Biopharma Limited

  公开号：US11202837B2

  公开（公告）日：2021-12-21

  The invention provides compounds comprising a therapeutic agent coupled to a carrier molecule, with a minimum coupling ratio of 5:1; wherein the carrier molecule is (i) an antibody fragment or derivative thereof or (ii) an antibody mimetic or derivative thereof; and wherein the therapeutic agents are coupled onto a lysine amino acid residue; and further wherein the therapeutic agent is not a photosensitising agent. There is also provided uses, methods relating to such compounds, as well as processes for their manufacture.

  本发明提供了由治疗剂与载体分子偶联而成的化合物，最小偶联比为5:1；其中载体分子为(i)抗体片段或其衍生物或(ii)抗体模拟物或其衍生物；治疗剂偶联在赖氨酸氨基酸残基上；以及治疗剂不是光敏剂。此外，还提供了与此类化合物有关的用途、方法及其制造工艺。
• BIOLOGICAL MATERIALS AND USES THEREOF
  申请人：Antikor Biopharma Limited

  公开号：US20170360951A1

  公开（公告）日：2017-12-21

  The invention provides compounds comprising a therapeutic agent coupled to a carrier molecule, with a minimum coupling ratio of 5:1; wherein the carrier molecule is (i) an antibody fragment or derivative thereof or (ii) an antibody mimetic or derivative thereof; and wherein the therapeutic agents are coupled onto a lysine amino acid residue; and further wherein the therapeutic agent is not a photosensitising agent. There is also provided uses, methods relating to such compounds, as well as processes for their manufacture.
• ANTI-ERBB2 ANTIBODY-DRUG CONJUGATE AND COMPOSITION THEREOF, PREPARATION METHOD THEREFOR, AND APPLICATION THEREOF
  申请人：SICHUAN KELUN-BIOTECH BIOPHARMACEUTICAL CO., LTD.

  公开号：US20190076438A1

  公开（公告）日：2019-03-14

  The present invention provides an anti-ErbB2 antibody-drug conjugate, a composition comprising the conjugate, a method for preparing the conjugate, use of the conjugate.
• ANTI-ERBB2 ANTIBODY-DRUG CONJUGATE AND COMPOSITION THEREOF, PREPARATION METHOD THEREFOR, AND USE THEREOF
  申请人：SICHUAN KELUN-BIOTECH BIOPHARMACEUTICAL CO., LTD.

  公开号：US20220008553A1

  公开（公告）日：2022-01-13

  Provided is a method for the prophylaxis or treatment of cancer, comprising administering to a patient in need thereof an antibody-drug conjugate represented by Formula (I), or a pharmaceutically acceptable salt or stereoisomer thereof, or a solvate of the foregoing, wherein A, X, Y, L, D and a are as defined herein.
• US9056141B2
  申请人：——

  公开号：US9056141B2

  公开（公告）日：2015-06-16