Lys-MCC-MDC | 1281816-04-3

• 物质功能分类: 医药中间体 - 原料药中间体
• 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: Lys-MCC-MDC
• 英文别名: Lysine-emtansine；(2S)-2-amino-6-[[4-[[3-[3-[[(2S)-1-[[(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]oxy]-1-oxopropan-2-yl]-methylamino]-3-oxopropyl]sulfanyl-2,5-dioxopyrrolidin-1-yl]methyl]cyclohexanecarbonyl]amino]hexanoic acid
• CAS: 1281816-04-3
• 化学式: C₅₃H₇₅ClN₆O₁₅S
• 分子量: 1103.73
• InChiKey: UBRZDBDIKWWPEN-YCPOLOASSA-N

物化性质

• 沸点：
  1249.6±65.0 °C(Predicted)
• 密度：
  1.36±0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  -0.2
• 重原子数：
  76
• 可旋转键数：
  19
• 环数：
  6.0
• sp3杂化的碳原子比例：
  0.66
• 拓扑面积：
  312
• 氢给体数：
  5
• 氢受体数：
  17

安全信息

• 储存条件：
  2-8℃

制备方法与用途

生物活性方面，Lys-SMCC-DM1 是 DM1 的活性代谢物。DM1 是一种微管（tubulin）抑制剂。

靶点为：

• Maytansinoids

反应信息

• 作为产物：
  描述：

  maytansinol 在 哌啶 、 4-二甲氨基吡啶 、 盐酸-N-乙基-Nˊ-(3-二甲氨基丙基)碳二亚胺 、 N,N-二异丙基乙胺 、 scandium tris(trifluoromethanesulfonate) 作用下， 以 甲醇 、 二氯甲烷 、 N,N-二甲基甲酰胺 、 乙腈 为溶剂， 反应 5.0h， 生成 Lys-MCC-MDC
  参考文献：
  名称：

  COMPOUNDS AND METHODS FOR THE TREATMENT OF ERB B2/NEU POSITIVE DISEASES

  摘要：

  本文揭示了与马坦西诺伊德药物结合的抗ERB B2/NEU抗体，用于定向传递到疾病组织。提供了与制备和使用此类药物共轭物以治疗癌症中的ERB B2/NEU阳性细胞有关的方法。

  公开号：

  US20140178413A1

文献信息

• COMPOUNDS AND METHODS FOR THE TREATMENT OF EGFR POSITIVE DISEASES
  申请人：Bio-Thera Solutions, Ltd., Co.

  公开号：US20140178412A1

  公开（公告）日：2014-06-26

  Disclosed herein are anti-EGFR antibodies conjugated with maytansinoid drugs for targeted delivery to disease tissues. Methods related to the preparation and uses of such antibody drug conjugates to treat EGFR positive cells in cancers are provided.

  本文披露了与马替南素类药物结合的抗EGFR抗体，用于靶向输送至疾病组织。提供了与制备和使用这种抗体药物结合物相关的方法，用于治疗癌症中的EGFR阳性细胞。
• MAYTANSINOID DERIVATIVES
  申请人：Bio-Thera Solutions, Ltd., Co.

  公开号：US20140178415A1

  公开（公告）日：2014-06-26

  Disclosed herein are maytansinoid drug linker derivatives which can be linked to a antigen binding unit (Abu), and maytansinoid drugs linked with an antigen binding unit (Drug-Linker-Antigen binding Unit: D-L-Abu), for targeted delivery to disease tissues. D-L-Abu, D-L-Abu derivatives, and methods relating to the use of such drug conjugates to treat antigen positive cells in cancers and immunological disorders are provided.

  本文披露了可能与抗原结合单位（Abu）连接的美坦西酮药物连接物的衍生物，以及与抗原结合单位连接的美坦西酮药物（药物-连接物-抗原结合单位：D-L-Abu），用于靶向递送至疾病组织。提供了D-L-Abu、D-L-Abu衍生物以及与使用这种药物共轭物治疗癌症和免疫性疾病中的抗原阳性细胞相关的方法。
• Metabolites of Antibody–Maytansinoid Conjugates: Characteristics and<i>in Vitro</i>Potencies
  作者：Wayne Widdison、Sharon Wilhelm、Karen Veale、Juliet Costoplus、Gregory Jones、Charlene Audette、Barbara Leece、Laura Bartle、Yelena Kovtun、Ravi Chari

  DOI：10.1021/mp5007757

  日期：2015.6.1

  Several antibody-maytansinoid conjugates (AMCs) are in clinical trials for the treatment of various cancers. Each of these conjugates can be metabolized by tumor cells to give cytotoxic maytansinoid metabolites that can kill targeted cells. In preclinical studies in mice, the cytotoxic metabolites initially formed in vivo are further processed in the mouse liver to give several oxidized metabolic species. In this work, the primary AMC metabolites were synthesized and incubated with human liver microsomes (HLMs) to determine if human liver would likely give the same metabolites as those formed in mouse liver. The results of these HLM metabolism studies as well as the subsequent syntheses of the resulting HLM oxidation products are presented. Syntheses of the minor impurities formed during the conjugation of AMCs were also conducted to determine their cytotoxicities and to establish how these impurities would be metabolized by HLM.
• COMPOUNDS AND METHODS FOR THE TREATMENT OF ERB B2/NEU POSITIVE DISEASES
  申请人：Bio-Thera Solutions, Ltd. Co.

  公开号：US20140178413A1

  公开（公告）日：2014-06-26

  Disclosed herein are anti-ERB B2/NEU antibodies conjugated with maytansinoid drugs for targeted delivery to disease tissues. Methods relating to the preparation and uses of such drug conjugates to treat ERB B2/NEU positive cells in cancers are provided.

  本文揭示了与马坦西诺伊德药物结合的抗ERB B2/NEU抗体，用于定向传递到疾病组织。提供了与制备和使用此类药物共轭物以治疗癌症中的ERB B2/NEU阳性细胞有关的方法。