duocarmycin C1 | 118292-35-6

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 喹啉及其衍生物
• 英文名称: duocarmycin C1
• 英文别名: Pyrindamycin B；methyl (2R,8S)-8-chloro-4-hydroxy-2-methyl-1-oxo-6-(5,6,7-trimethoxy-1H-indole-2-carbonyl)-3,7,8,9-tetrahydropyrrolo[3,2-f]quinoline-2-carboxylate
• CAS: 118292-35-6
• 化学式: C₂₆H₂₆ClN₃O₈
• 分子量: 543.961
• InChiKey: ILRQRCTVPANBBE-GWQKEKGPSA-N

物化性质

• 沸点：
  805.6±65.0 °C(Predicted)
• 密度：
  1.52±0.1 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)：
  3.5
• 重原子数：
  38
• 可旋转键数：
  6
• 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

安全信息

• 海关编码：
  2933499090

制备方法与用途

生物活性

Pyrindamycin B 是一种对抗革兰氏阳性菌和革兰氏阴性菌的抗生素，并且已经深入研究了其对小鼠 P388 白血病敏感及耐药细胞的作用。

反应信息

• 作为反应物：
  描述：

  duocarmycin C1 在 sodium periodate 、 溶剂黄146 作用下， 以 甲醇 为溶剂， 反应 3.0h， 以43%的产率得到
  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
• 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。
• 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").
• [EN] METHODS FOR THE USE OF A B7-H3 ANTIBODY-DRUG CONJUGATE ALONE OR IN COMBINATION<br/>[FR] MÉTHODES D'UTILISATION D'UN CONJUGUÉ ANTICORPS B7-H3-MÉDICAMENT SEUL OU EN ASSOCIATION
  申请人：MACROGENICS INC

  公开号：WO2021231309A1

  公开（公告）日：2021-11-18

  The present invention is directed to dosing regimens for administering a humanized anti- B7-H3 antibody conjugated to at least one duocarmycin moiety (a "B7-H3-ADC") for the treatment of cancer, particularly a cancer associated with expression of B7-H3. The invention particularly concerns the use of such B7-H3-ADC optionally in combination with a PD-1 binding molecule for the treatment of cancer. The invention particularly concerns the use of such B7-H3-ADC and an anti-PD-1 antibody or a PD-1 X LAG-3 bispecific molecule. The invention is directed to the use of such molecules, and to the use of pharmaceutical compositions and pharmaceutical kits that contain such molecules and that facilitate the use of such dosing regimens in the treatment of cancer.
• Duocarmycins, Potent Antitumor Antibiotics Produced by Streptomyces sp. Structures and Chemistry.
  作者：Tohru YASUZAWA、Ken'ichi MUROI、Michio ICHIMURA、Isami TAKAHASHI、Tatsuhiro OGAWA、Keiichi TAKAHASHI、Hiroshi SANO、Yutaka SAITOH

  DOI：10.1248/cpb.43.378

  日期：——

  Seven novel potent antitumor antibiotics, duocarmycins A (1), C1 (2), C2 (3), D (4), B1 (5), B2 (6) and SA (7), were isolated from three independently collected Streptomyces sp. The complete structures, including absolute stereochemistry, were determined by spectral and chemical studies of those duocarmycins and several derivatives. Duocarmycins A (1) and SA (7) possess a 1,2,7,7a-tetrahydrocycloprop[1

  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。