duocarmycin C2 | 118292-36-7

• 分子结构分类: 有机化合物 - 有机酸及其衍生物 - 羧酸及其衍生物
• 英文名称: duocarmycin C2
• 英文别名: Pyrindamycin A；methyl (2R,8S)-8-(chloromethyl)-4-hydroxy-2-methyl-1-oxo-6-(5,6,7-trimethoxy-1H-indole-2-carbonyl)-7,8-dihydro-3H-pyrrolo[3,2-e]indole-2-carboxylate
• CAS: 118292-36-7
• 化学式: C₂₆H₂₆ClN₃O₈
• 分子量: 543.961
• InChiKey: BOGFADYROAVVTF-MZHQLVBMSA-N

物化性质

• 溶解度：
  溶于二甲基亚砜

计算性质

• 辛醇/水分配系数(LogP)：
  3.3
• 重原子数：
  38
• 可旋转键数：
  7
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.35
• 拓扑面积：
  139
• 氢给体数：
  3
• 氢受体数：
  9

制备方法与用途

生物活性

Pyrindamycin A（吡啶霉素 A）是一种抑制 DNA 合成的抗生素。研究表明，它展现出显著的抗肿瘤活性，尤其对鼠白血病细胞表现出良好的抗肿瘤效果，并且对小鼠和人肿瘤细胞系具有强烈的细胞毒性作用，特别是在对抗多柔比星耐药细胞方面表现突出。

反应信息

• 作为反应物：
  描述：

  duocarmycin C2 、 腺嘌呤 以86%的产率得到
  参考文献：
  名称：

  BOGER, DALE L.;ISHIZAKI, TAKAYOSHI;ZARRINMAYEH, HAMIDEH, J. AMER. CHEM. SOC., 113,(1991) N7, C. 6645-6649

  摘要：

  DOI：
• 作为产物：
  描述：

  倍癌霉素A 在 盐酸 作用下， 以 丙酮 为溶剂， 反应 0.02h， 以0.2 mg的产率得到duocarmycin C1
  参考文献：
  名称：

  Duocarmycins，链霉菌属（Streptomyces sp。）生产的有效抗肿瘤抗生素。结构和化学。

  摘要：

  从三个独立收集的链霉菌属菌种中分离出七种新型强效抗肿瘤抗生素，杜卡霉素A（1），C1（2），C2（3），D（4），B1（5），B2（6）和SA（7）。 。完整的结构，包括绝对的立体化学，是通过对那些杜卡霉素和几种衍生物的光谱和化学研究确定的。Duocarmycins A（1）和SA（7）具有1,2,7,7a-四氢环丙[1,2-c]吲哚-4-一亚基，这是与链霉菌中CC-1065（10）相同的药效基团zelensis。

  DOI：

  10.1248/cpb.43.378

文献信息

• B7-H3 binding molecules, antibody drug conjugates thereof and methods of use thereof
  申请人：MacroGenics, Inc.

  公开号：US10961311B2

  公开（公告）日：2021-03-30

  The present invention is directed to novel B7-H3-binding molecules capable of binding to human and non-human B7-H3, and in particular to such molecules that are cross-reactive with B7-H3 of a non-human primate (e.g., a cynomolgus monkey). The invention additionally pertains to B7-H3-binding molecules that comprise Variable Light Chain and/or Variable Heavy Chain (VH) Domains that have been humanized and/or deimmunized so as to exhibit a reduced immunogenicity upon administration to recipient subjects. The invention particularly pertains to bispecific, trispecific or multispecific B7-H3-binding molecules, including bispecific diabodies, BiTEs, bispecific antibodies, trivalent binding molecules, etc. that comprise: (i) such B7-H3-binding Variable Domains and (ii) a domain capable of binding to an epitope of a molecule present on the surface of an effector cell. The invention is also directed to pharmaceutical compositions that contain any of such B7-H3-binding molecules, and to methods involving the use of any of such B7-H3-binding molecules in the treatment of cancer and other diseases and conditions. The invention also particularly pertains to a molecule that comprises the human B7-H3 binding domain of a humanized anti-human B7-H3 antibody conjugated to at least one drug moiety (a “B7-H3-ADC”). The invention is also directed to pharmaceutical compositions that contain such B7-H3-ADCs, and to methods involving the use of any of such B7-H3-ADCs in the treatment of cancer and other diseases and conditions.

  本发明涉及能够与人类和非人类 B7-H3 结合的新型 B7-H3 结合分子，特别是与非人灵长类动物（如猕猴）的 B7-H3 具有交叉反应的分子。此外，本发明还涉及包含可变轻链和/或可变重链（VH）域的 B7-H3 结合分子，这些分子已被人源化和/或去免疫化，以便在给受试者用药时显示出较低的免疫原性。本发明尤其涉及双特异性、三特异性或多特异性 B7-H3 结合分子，包括双特异性二抗体、双特异性抗体、双特异性抗体、三价结合分子等，这些分子包含：(i) 这种 B7-H3 结合可变区；(ii) 能够与效应细胞表面存在的分子表位结合的结构域。本发明还涉及含有任何此类 B7-H3 结合分子的药物组合物，以及涉及使用任何此类 B7-H3 结合分子治疗癌症及其他疾病和病症的方法。本发明还特别涉及一种分子，该分子包括与至少一种药物分子（"B7-H3-ADC"）共轭的人源化抗人 B7-H3 抗体的人 B7-H3 结合域。本发明还涉及含有此类 B7-H3-ADC 的药物组合物，以及涉及使用任何此类 B7-H3-ADC 治疗癌症及其他疾病和病症的方法。
• BOGER, DALE L.;ISHIZAKI, TAKAYOSHI;ZARRINMAYEH, HAMIDEH, J. AMER. CHEM. SOC., 113,(1991) N7, C. 6645-6649
  作者：BOGER, DALE L.、ISHIZAKI, TAKAYOSHI、ZARRINMAYEH, HAMIDEH

  DOI：——

  日期：——
• Boger, Dale L.; Ishizaki, Takayoshi; Zarrinmayeh, Hamideh, Journal of the American Chemical Society, 1991, vol. 113, # 17, p. 6645 - 6649
  作者：Boger, Dale L.、Ishizaki, Takayoshi、Zarrinmayeh, Hamideh

  DOI：——

  日期：——
• NOVEL B7-H3 BINDING MOLECULES, ANTIBODY DRUG CONJUGATES THEREOF AND METHODS OF USE THEREOF
  申请人：MacroGenics, Inc.

  公开号：US20190127471A1

  公开（公告）日：2019-05-02

  The present invention is directed to novel B7-H3-binding molecules capable of binding to human and non-human B7-H3, and in particular to such molecules that are cross-reactive with B7-H3 of a non-human primate (e.g., a cynomolgus monkey). The invention additionally pertains to B7-H3-binding molecules that comprise Variable Light Chain and/or Variable Heavy Chain (VH) Domains that have been humanized and/or deimmunized so as to exhibit a reduced immunogenicity upon administration to recipient subjects. The invention particularly pertains to bispecific, trispecific or multispecific B7-H3-binding molecules, including bispecific diabodies, BiTEs, bispecific antibodies, trivalent binding molecules, etc. that comprise: (i) such B7-H3-binding Variable Domains and (ii) a domain capable of binding to an epitope of a molecule present on the surface of an effector cell. The invention is also directed to pharmaceutical compositions that contain any of such B7-H3-binding molecules, and to methods involving the use of any of such B7-H3-binding molecules in the treatment of cancer and other diseases and conditions. The invention also particularly pertains to a molecule that comprises the human B7-H3 binding domain of a humanized anti-human B7-H3 antibody conjugated to at least one drug moiety (a “B7-H3-ADC”). The invention is also directed to pharmaceutical compositions that contain such B7-H3-ADCs, and to methods involving the use of any of such B7-H3-ADCs in the treatment of cancer and other diseases and conditions.
• [EN] NOVEL B7-H3 BINDING MOLECULES, ANTIBODY DRUG CONJUGATES THEREOF AND METHODS OF USE THEREOF<br/>[FR] NOUVELLES MOLÉCULES DE LIAISON À B7-H3, LEURS CONJUGUÉS ANTICORPS-MÉDICAMENTS ET LEURS PROCÉDÉS D'UTILISATION
  申请人：MACROGENICS INC

  公开号：WO2017180813A1

  公开（公告）日：2017-10-19

  The present invention is directed to novel B7-H3-binding molecules capable of binding to human and non-human B7-H3, and in particular to such molecules that are cross-reactive with B7-H3 of a non-human primate (e.g., a cynomolgus monkey). The invention additionally pertains to B7-H3-binding molecules that comprise Variable Light Chain and/or Variable Heavy Chain (VH) Domains that have been humanized and/or deimmunized so as to exhibit a reduced immunogenicity upon administration to recipient subjects. The invention particularly pertains to bispecific, trispecific or multispecific B7-H3-binding molecules, including bispecific diabodies, BiTEs, bispecific antibodies, trivalent binding molecules, etc. that comprise: (i) such B7-H3-binding Variable Domains and (ii) a domain capable of binding to an epitope of a molecule present on the surface of an effector cell. The invention also particularly pertains to a molecule that comprises the human B7-H3 binding domain of a humanized anti-human B7-H3 antibody conjugated to at least one drug moiety (a "B7-H3-ADC").