2-[[(2S)-2-(dimethylamino)-3-methylbutanoyl]amino]-N-[(3R,4S,5S)-3-methoxy-1-[(2S)-2-[(1R,2R)-1-methoxy-2-methyl-3-oxo-3-(2-phenylethylamino)propyl]pyrrolidin-1-yl]-5-methyl-1-oxoheptan-4-yl]-N,3-dimethylbutanamide

• 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: 2-[[(2S)-2-(dimethylamino)-3-methylbutanoyl]amino]-N-[(3R,4S,5S)-3-methoxy-1-[(2S)-2-[(1R,2R)-1-methoxy-2-methyl-3-oxo-3-(2-phenylethylamino)propyl]pyrrolidin-1-yl]-5-methyl-1-oxoheptan-4-yl]-N,3-dimethylbutanamide
• 化学式: C₃₉H₆₇N₅O₆
• 分子量: 702.0
• InChiKey: DZMVCVHATYROOS-CKXIHPEFSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  5.2
• 重原子数：
  50
• 可旋转键数：
  20
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.74
• 拓扑面积：
  121
• 氢给体数：
  2
• 氢受体数：
  7

文献信息

• Targeting tumor cells with chemotherapeutic agents conjugated to matriptase antibodies
  申请人：Rutgers, The State University of New Jersey

  公开号：US10376597B2

  公开（公告）日：2019-08-13

  The present invention relates to matriptase antibodies and immunoconjugates of matriptase antibodies with cytotoxic agents and the use thereof for killing or inhibiting the growth of matriptase-expressing cancer cells, such as those of multiple myeloma and breast cancers. In particular, immunoconjugates comprising a matriptase monoclonal antibody and anticancer agents such as auristatin, including monomethyl auristatin E (MMAE) and monomethyl auristatin F (MMAF) are introduced, which have potent antitumor activity in vivo. Moreover, importantly; there was no weight loss or other evidence of toxicity in the animals, indicating that no significant free drug was released into the circulation from the conjugate. The present invention also provides compositions comprising these new immunoconjugates and use of them for treatment of malignancies comprising cells that express matriptase. In addition, administration of a matriptase antibody or immunoconjugates of a matriptase antibody and a cytotoxic agent in combination with administration of an immunomodulatory agent, such as thalidomide or an analog thereof, provides a more effective treatment of these cancers.

  本发明涉及matriptase抗体和matriptase抗体与细胞毒剂的免疫共轭物，及其用于杀死或抑制表达matriptase的癌细胞，如多发性骨髓瘤和乳腺癌细胞的生长。特别是，介绍了由马立替酶单克隆抗体和抗癌剂（如金丝桃素，包括单甲基金丝桃素 E（MMAE）和单甲基金丝桃素 F（MMAF））组成的免疫共轭物，它们在体内具有强效抗肿瘤活性。此外，重要的是，动物没有体重减轻或其他毒性迹象，这表明共轭物中没有大量游离药物释放到血液循环中。本发明还提供了包含这些新型免疫共轭物的组合物，并将其用于治疗包含表达马立普酶的细胞的恶性肿瘤。此外，将马特普酶抗体或马特普酶抗体与细胞毒剂的免疫结合剂与沙利度胺或其类似物等免疫调节剂联合使用，可更有效地治疗这些癌症。
• TARGETING TUMOR CELLS WITH CHEMOTHERAPEUTIC AGENTS CONJUGATED TO MATRIPTASE ANTIBODIES
  申请人：Rutgers, The State University of New Jersey

  公开号：US20160263244A1

  公开（公告）日：2016-09-15

  The present invention relates to matriptase antibodies and immunoconjugates of matriptase antibodies with cytotoxic agents and the use thereof for killing or inhibiting the growth of matriptase-expressing cancer cells, such as those of multiple myeloma and breast cancers. In particular, immunoconjugates comprising a matriptase monoclonal antibody and anticancer agents such as auristatin, including monomethyl auristatin E (MMAE) and monomethyl auristatin F (MMAF) are introduced, which have potent antitumor activity in vivo. Moreover, importantly; there was no weight loss or other evidence of toxicity in the animals, indicating that no significant free drug was released into the circulation from the conjugate. The present invention also provides compositions comprising these new immunoconjugates and use of them for treatment of malignancies comprising cells that express matriptase. In addition, administration of a matriptase antibody or immunoconjugates of a matriptase antibody and a cytotoxic agent in combination with administration of an immunomodulatory agent, such as thalidomide or an analog thereof, provides a more effective treatment of these cancers.
• TARGETING TUMOR CELLS WITH CHEMOTHERAPEUTIC AGENTS CONJUGATED TO ANTI-MATRIPTASE ANTIBODIES BY IN VIVO CLEAVABLE LINKING MOIETIES
  申请人：Rutgers, The State University of New Jersey

  公开号：US20190151464A1

  公开（公告）日：2019-05-23

  The present invention relates to anti-matriptase antibodies and immunoconjugates of anti-matriptase antibodies with cytotoxic agents and the use thereof for killing or inhibiting the growth of matriptase-expressing cancer cells, such as those of multiple myeloma and breast cancers. In particular, immunoconjugates comprising an anti-matriptase monoclonal antibody and anticancer agents such as auristatin, including monomethyl auristatin E (MMAE) and monomethyl auristatin F (MMAF) are introduced, which have potent antitumor activity in vivo. Moreover, importantly; there was no weight loss or other evidence of toxicity in the animals, indicating that no significant free drug was released into the circulation from the conjugate. The present invention also provides compositions comprising these new immunoconjugates and use of them for treatment of malignancies comprising cells that express matriptase. In addition, administration of an anti-matriptase antibody or immunoconjugates of an anti-matriptase antibody and a cytotoxic agent in combination with administration of an immunomodulatory agent, such as thalidomide or an analog thereof, provides a more effective treatment of these cancers.
• US9849192B2
  申请人：——

  公开号：US9849192B2

  公开（公告）日：2017-12-26