[4-[[6-Amino-2-[[2-(2-amino-2-oxoethoxy)acetyl]amino]hexanoyl]amino]phenyl]methyl (10,19-diethyl-7-hydroxy-14,18-dioxo-17-oxa-3,13-diazapentacyclo[11.8.0.02,11.04,9.015,20]henicosa-1(21),2,4(9),5,7,10,15(20)-heptaen-19-yl) carbonate

• 分子结构分类: 有机化合物 - 生物碱及其衍生物 - 喜树碱
• 英文名称: [4-[[6-Amino-2-[[2-(2-amino-2-oxoethoxy)acetyl]amino]hexanoyl]amino]phenyl]methyl (10,19-diethyl-7-hydroxy-14,18-dioxo-17-oxa-3,13-diazapentacyclo[11.8.0.02,11.04,9.015,20]henicosa-1(21),2,4(9),5,7,10,15(20)-heptaen-19-yl) carbonate
• 英文别名: [4-[[6-amino-2-[[2-(2-amino-2-oxoethoxy)acetyl]amino]hexanoyl]amino]phenyl]methyl (10,19-diethyl-7-hydroxy-14,18-dioxo-17-oxa-3,13-diazapentacyclo[11.8.0.02,11.04,9.015,20]henicosa-1(21),2,4(9),5,7,10,15(20)-heptaen-19-yl) carbonate
• 化学式: C₄₀H₄₄N₆O₁₁
• 分子量: 784.8
• InChiKey: QHHKJRJWGVZWJY-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.4
• 重原子数：
  57
• 可旋转键数：
  18
• 环数：
  6.0
• sp3杂化的碳原子比例：
  0.38
• 拓扑面积：
  252
• 氢给体数：
  5
• 氢受体数：
  13

文献信息

• Dosages of Immunoconjugates of Antibodies and SN-38 for Improved Efficacy and Decreased Toxicity
  申请人：Immunomedics, Inc.

  公开号：US20140170063A1

  公开（公告）日：2014-06-19

  The present invention relates to therapeutic immunoconjugates comprising SN-38 attached to an antibody or antigen-binding antibody fragment. The antibody may bind to EGP-1 ROP-2), CEACAM5, CEACAM6, CD74, CD19, CD20, CD22, CSAp, HLA-DR, AFP or MUC5ac and the immunoconjugate may be administered at a dosage of between 4 mg/kg and 24 mg/kg, preferably 4, 6, 8, 9, 10, 12, 16 or 18 mg/kg. When administered at specified dosages and schedules, the immunoconjugate can reduce solid tumors in size, reduce or eliminate metastases and is effective to treat cancers resistant to standard therapies, such as radiation therapy, chemotherapy or immunotherapy.

  本发明涉及治疗免疫结合物，其包括将SN-38连接到抗体或抗原结合抗体片段上。抗体可以结合到EGP-1 ROP-2，CEACAM5，CEACAM6，CD74，CD19，CD20，CD22，CSAp，HLA-DR，AFP或MUC5ac，并且免疫结合物可以以每公斤4毫克至24毫克的剂量给予，最好是4、6、8、9、10、12、16或18毫克/公斤。当以指定的剂量和方案给药时，免疫结合物可以减小实体肿瘤的大小，减少或消除转移，并且对于对标准治疗（如放疗、化疗或免疫疗法）具有抗性的癌症有效。
• Therapy for metastatic urothelial cancer with the antibody-drug conjugate, sacituzumab govitecan (IMMU-132)
  申请人：Immunomedics, Inc.

  公开号：US11052081B2

  公开（公告）日：2021-07-06

  The present invention relates to therapeutic ADCs comprising SN-38 attached to an anti-Trop-2 antibody or antigen-binding antibody fragment. The ADC may be administered at a dosage of between 4 mg/kg and 18 mg/kg, preferably 4, 6, 8, 9, 10, 12, 16 or 18 mg/kg, most preferably 8 to 10 mg/kg. When administered at specified dosages and schedules, the ADC can reduce solid tumors in size, reduce or eliminate metastases and is effective to treat cancers resistant to standard therapies, such as radiation therapy, chemotherapy or immunotherapy. Preferably, the ADC is administered in combination with one or more other therapeutic agents, such as a PARP inhibitor, a microtubule inhibitor, a Bruton kinase inhibitor or a PI3K inhibitor. Most preferably, the ADC is of use for treating a Trop-2 expressing cancer, such as metastatic urothelial cancer.

  本发明涉及治疗用 ADC，该 ADC 由附着于抗 Trop-2 抗体或抗原结合抗体片段的 SN-38 组成。ADC 的给药剂量为 4 毫克/千克至 18 毫克/千克，优选 4、6、8、9、10、12、16 或 18 毫克/千克，最优选 8 至 10 毫克/千克。按规定的剂量和疗程给药时，ADC 可以缩小实体瘤的体积，减少或消除转移，并能有效治疗对标准疗法（如放疗、化疗或免疫疗法）耐药的癌症。优选地，ADC 与一种或多种其他治疗剂联合使用，如 PARP 抑制剂、微管抑制剂、布鲁顿激酶抑制剂或 PI3K 抑制剂。最优选的是，ADC 用于治疗表达 Trop-2 的癌症，如转移性尿道癌。
• IMMUNOCONJUGATES WITH AN INTRACELLULARLY-CLEAVABLE LINKAGE
  申请人：Immunomedics, Inc.

  公开号：EP2396036B1

  公开（公告）日：2017-06-28
• THERAPY OF SMALL-CELL LUNG CANCER (SCLC) WITH A TOPOISOMERASE-I INHIBITING ANTIBODY-DRUG CONJUGATE (ADC) TARGETING TROP-2
  申请人：Immunomedics, Inc.

  公开号：US20180185351A1

  公开（公告）日：2018-07-05

  The present invention relates to treatment of SCLC with therapeutic ADCs comprising a drug attached to an anti-Trop-2 antibody or antigen-binding antibody fragment. Preferably, the drug is SN-38. More preferably, the antibody is an hRS7 antibody and the ADC is sacituzumab govitecan. The ADC may be administered at a dosage of between 4 mg/kg and 16 mg/kg, preferably 4, 6, 8, 9, 10, 12, or 16 mg/kg, mostly preferably 8 to 10 mg/kg. When administered at specified dosages and schedules, the ADC can reduce solid tumors in size, reduce or eliminate metastases and is effective to treat cancers resistant to standard therapies, such as radiation therapy, chemotherapy or immunotherapy. Surprisingly, the ADC is effective to treat cancers that are refractory to or relapsed from irinotecan or topotecan. Preferably, the ADC is administered as a combination therapy with one or more other anti-cancer treatments, such as carboplatin or cisplatinum.
• US9028833B2
  申请人：——

  公开号：US9028833B2

  公开（公告）日：2015-05-12