单甲基澳瑞他汀 F | 745017-94-1

• 物质功能分类: 生物化工 - 生化试剂 - 激动剂抑制剂
• 分子结构分类: 有机化合物 - 有机酸及其衍生物 - 肽模拟物
• 中文名称: 单甲基澳瑞他汀 F
• 中文别名: 一甲基澳瑞他汀F；一甲基澳瑞他汀 F
• 英文名称: Monomethylauristatin F
• 英文别名: (2S)-2-[[(2R,3R)-3-methoxy-3-[(2S)-1-[(3R,5S)-3-methoxy-5-methyl-4-[methyl-[(2S)-3-methyl-2-[[(2S)-3-methyl-2-(methylamino)butanoyl]amino]butanoyl]amino]heptanoyl]pyrrolidin-2-yl]-2-methylpropanoyl]amino]-3-phenylpropanoic acid
• CAS: 745017-94-1
• 化学式: C₃₉H₆₅N₅O₈
• 分子量: 732.0
• InChiKey: MFRNYXJJRJQHNW-NARUGQRUSA-N

物化性质

• 沸点：
  896.8±65.0 °C(Predicted)
• 密度：
  1.116±0.06 g/cm3(Predicted)
• 溶解度：
  溶于二甲基亚砜

计算性质

• 辛醇/水分配系数(LogP)：
  2.1
• 重原子数：
  52
• 可旋转键数：
  21
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.72
• 拓扑面积：
  167
• 氢给体数：
  4
• 氢受体数：
  9

安全信息

• 危险性防范说明：
  P261,P305+P351+P338
• 危险性描述：
  H302,H315,H319,H335

制备方法与用途

用途

一甲基澳瑞他汀 F用作科学研究和化学试剂等领域。

应用

一甲基澳瑞他汀 F是抗微管药。有力的有丝分裂抑制剂。

用途

MMAF是一种合成的抗肿瘤药物。它是一些实验性抗癌抗体-药物偶联物的一部分，如vorsetuzumab mafodotin和SGN-CD19A。在MMAF-抗体偶联物的国际非专利名称中，mafodotin指的是MMAF及其与抗体的连接结构。MMAF实际上是去甲基奥利斯特汀F;也就是说，N-末端氨基只有一个甲基取代基。

生物活性

MMAF (Monomethylauristatin F) 是一种合成抗肿瘤药，是 tubulin 聚合的有效抑制剂。MMAF（Monomethylauristatin F）可被用作抗体偶联药物(ADCs)中的细胞毒性成分，例如 vorsetuzumab mafodotin，ABT-414和SGN-CD19A。

靶点

Target	Value
Tubulin ()

体外研究

MMAF inhibits anaplastic large cell lymphoma Karpas 299, breast carcinoma H3396, renal cell carcinoma 786-O and Caki-1 cells with IC ₅₀ s of 119, 105, 257 and 200 nM in vitro cytotoxicity assay.

体内研究

The maximum tolerated dose in mice of MMAF (Monomethylauristatin F) (>16 mg/kg) is much higher than MMAF (Monomethylauristatin F) (1 mg/kg). cAC10-L1-MMAF ₄ has an MTD of 50 mg/kg in mice and 15 mg/kg in rats. The corresponding cAC10-L4-MMAF ₄ ADC was much less toxic, having MTDs in mice and rats of >150 mg/ kg and 90 mg/kg in rats, respectively.

文献信息

• Antibody-Drug Conjugates and Related Compounds, Compositions, and Methods
  申请人：Igenica, Inc.

  公开号：US20130224228A1

  公开（公告）日：2013-08-29

  Antibody-cytotoxin antibody-drug conjugates and related compounds, such as linker-cytotoxin conjugates and the linkers used to make them, tubulysin analogs, and intermediates in their synthesis; compositions; and methods, including methods of treating cancers.

  抗体-细胞毒素抗体-药物偶联物及相关化合物，例如连接剂-细胞毒素偶联物和用于制造它们的连接剂，管芽菌素类似物和它们合成中的中间体；组成物；和方法，包括治疗癌症的方法。
• LIGAND-CYTOTOXICITY DRUG CONJUGATE, PREPARATION METHOD THEREFOR, AND USES THEREOF
  申请人：Shanghai Hengrui Pharmaceutical Co., Ltd.

  公开号：EP3100731A1

  公开（公告）日：2016-12-07

  The present invention relates to a ligand-cytotoxic drug conjugate, preparation method and pharmaceutical use thereof. More specifically, the present invention provides a ligand-cytotoxic drug conjugate of general formula Pc-(X-Y-D)n , their preparation method and use of the ligand-cytotoxic drug conjugate and a pharmaceutical composition containing the same in the preparation of a medicament for the treatment of cancer via receptor modulation.

  本发明涉及一种配体-细胞毒性药物共轭物、其制备方法和药物用途。更具体地说，本发明提供了一种通式为 Pc-(X-Y-D)n的配体-毒性药物共轭物、其制备方法以及该配体-毒性药物共轭物和含有该配体-毒性药物共轭物的药物组合物在制备通过受体调节治疗癌症的药物中的用途。
• ANTI-C-MET ANTIBODY AND ANTI-C-MET ANTIBODY-CYTOTOXIC DRUG CONJUGATE AND PHARMACEUTICAL USE THEREOF
  申请人：Suzhou Suncadia Biopharmaceuticals Co., Ltd.

  公开号：EP3284751A1

  公开（公告）日：2018-02-21

  Provided are an anti-c-Met antibody or antigen binding fragment, and an anti-c-Met antibody-cytotoxic drug conjugate, wherein the antibody or antigen binding fragment is a chimeric antibody or a humanized antibody. Also provided are a pharmaceutical composition containing a humanized anti-c-Met antibody or antigen binding fragment, antibody-cytotoxic drug conjugate, or a pharmaceutically acceptable salt or solvent compound thereof, applied in the treatment of cancer.

  本发明提供了一种抗-Met 抗体或抗原结合片段，以及一种抗-Met 抗体-细胞毒性药物共轭物，其中抗体或抗原结合片段是嵌合抗体或人源化抗体。还提供了一种药物组合物，其中含有人源化的抗-Met抗体或抗原结合片段、抗体-细胞毒性药物共轭物或其药学上可接受的盐或溶剂化物，可用于治疗癌症。
• MEDICAL USE OF ANTI-C MET ANTIBODY-CYTOTOXIC DRUG CONJUGATE
  申请人：Suzhou Suncadia Biopharmaceuticals Co., Ltd.

  公开号：EP3545974A1

  公开（公告）日：2019-10-02

  Disclosed is the medical use of an anti-c Met antibody-cytotoxic drug conjugate. In particular, disclosed are an anti-c-Met antibody, an antigen-binding fragment of c-Met, a chimeric antibody and humanized antibody comprising the anti-c-Met antibody CDR region, and an antibody-cytotoxic drug conjugate thereof or pharmaceutically acceptable salt or solvate thereof, and the use of a pharmaceutical composition comprising the humanized anti-c-Met antibody and antigen-binding fragment and the antibody-cytotoxic drug conjugate thereof or the pharmaceutically acceptable salt or solvate thereof as an anti-hepatoma drug.

  本研究公开了一种抗 c-Met 抗体-细胞毒性药物共轭物的医疗用途。特别是，公开了一种抗-Met 抗体、c-Met 的抗原结合片段、包含抗-Met 抗体 CDR 区的嵌合抗体和人源化抗体，及其抗体-细胞毒性药物共轭物或其药学上可接受的盐或溶液、以及将包含人源化抗-Met抗体和抗原结合片段及其抗体-细胞毒性药物共轭物或其药学上可接受的盐或溶液的药物组合物用作抗肝癌药物。
• LIGAND-CYTOTOXIC DRUG CONJUGATE, PREPARATION METHOD THEREOF, AND USES THEREOF
  申请人：SHANGHAI HENGRUI PHARMACEUTICAL CO.,LTD.

  公开号：US20170002090A1

  公开（公告）日：2017-01-05

  Ligand-cytotoxic drug conjugates, pharmaceutical compositions, preparation methods, and pharmaceutical uses thereof are provided. More specifically, a ligand-cytotoxic drug conjugate of general formula Pc-(X-Y-D) n is provided. The ligand-cytotoxic drug conjugate can be used to treat cancer via receptor modulation.