[(19S)-10,19-diethyl-19-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-7-yl] 4-piperidin-1-ylpiperidine-1-carboxylate;[(2R,3R,4S,5R,6R)-2-[(2S,3S,4R,5R)-3,4-disulfonatooxy-2,5-bis(sulfonatooxymethyl)oxolan-2-yl]oxy-3,5-disulfonatooxy-6-(sulfonatooxymethyl)oxan-4-yl] sulfate

• 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: [(19S)-10,19-diethyl-19-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-7-yl] 4-piperidin-1-ylpiperidine-1-carboxylate;[(2R,3R,4S,5R,6R)-2-[(2S,3S,4R,5R)-3,4-disulfonatooxy-2,5-bis(sulfonatooxymethyl)oxolan-2-yl]oxy-3,5-disulfonatooxy-6-(sulfonatooxymethyl)oxan-4-yl] sulfate
• 化学式: C45H52N4O41S8-8
• 分子量: 1561.4
• InChiKey: PMZSPINGJVBHAT-UVYDIPIJSA-F

计算性质

• 辛醇/水分配系数(LogP)：
  -5.43
• 重原子数：
  98
• 可旋转键数：
  18
• 环数：
  9.0
• sp3杂化的碳原子比例：
  0.64
• 拓扑面积：
  739
• 氢给体数：
  1
• 氢受体数：
  43

文献信息

• Stabilizing Camptothecin Pharmaceutical Compositions
  申请人：Ipsen Biopharm Ltd.

  公开号：US20170319573A1

  公开（公告）日：2017-11-09

  Irinotecan phospholipid liposomes with improved storage stability are provided, with related methods of treatment and manufacture. The irinotecan liposomes can have reduced formation of lyso-phosphatidylcholine (lyso-PC) during storage, and prior to administration to a patient.

  提供具有改善储存稳定性的伊立替康磷脂脂质体，以及相关的治疗和制造方法。伊立替康脂质体在储存期间和在给患者之前可以减少溶血磷脂酰胆碱（lyso-PC）的形成。
• [EN] INHIBITING ATAXIA TELANGIECTASIA AND RAD3-RELATED PROTEIN (ATR)<br/>[FR] INHIBITION DE LA PROTÉINE ASSOCIÉE À L'ATAXIE TÉLANGIECTASIE ET À RAD3 (ATR)
  申请人：MERRIMACK PHARMACEUTICALS INC

  公开号：WO2017123588A1

  公开（公告）日：2017-07-20

  Novel compounds inhibiting ATR protein kinase include compounds of formula (I) disclosed herein, as well as liposome formulations comprising ATR protein kinase inhibitor compounds. The compositions are useful for the treatment of cancer.

  新型化合物抑制ATR蛋白激酶，包括公式（I）所披露的化合物，以及包含ATR蛋白激酶抑制剂化合物的脂质体配方。该组合物对治疗癌症有用。
• COMBINATIONS OF LIPOSOMAL IRINOTECAN, 5-FU AND LEUCOVORIN FOR THE TREATMENT OF PANCREATIC CANCER
  申请人：Ipsen Biopharm Ltd.

  公开号：EP3266456A1

  公开（公告）日：2018-01-10

  Provided are methods for treating pancreatic cancer in a patient by administering liposomal irinotecan (MM-398) alone or in combination with additional therapeutic agents. In one embodiment, the liposomal irinotecan (MM-398) is co-administered with 5-fluorouracil and leucovorin.

  本文提供了通过单独使用或与其他治疗剂联合使用脂质体伊立替康（MM-398）治疗患者胰腺癌的方法。在一个实施方案中，脂质体伊立替康（MM-398）与 5-氟尿嘧啶和亮菌甲素联合给药。
• Stabilizing camptothecin pharmaceutical compositions
  申请人：Ipsen Biopharm Ltd.

  公开号：US10456360B2

  公开（公告）日：2019-10-29

  Irinotecan phospholipid liposomes with improved storage stability are provided, with related methods of treatment and manufacture. The irinotecan liposomes can have reduced formation of lyso-phosphatidylcholine (lyso-PC) during storage, and prior to administration to a patient.

  本研究提供了具有更好储存稳定性的伊立替康磷脂脂质体，以及相关的处理和制造方法。伊立替康脂质体在贮存期间和给病人用药前可减少溶血磷脂酰胆碱（溶血 PC）的形成。
• Combination therapy for cancer treatment
  申请人：Ipsen Biopharm Ltd.

  公开号：US10478428B2

  公开（公告）日：2019-11-19

  Combination therapies for treating cancer comprising administration of a topoisomerase-1 inhibitor and a PARP inhibitor are provided. The topoisomerase-1 inhibitor can be delivered as a liposomal formulation that provides for prolonged accumulation of the topoisomerase-1 inhibitor within a tumor relative to outside of the tumor. Therapeutic benefit can thereby be obtained by delaying the administration of the PARP inhibitor after each administration of a liposomal irinotecan formulation until the accumulation of the topoisomerase inhibitor in the tumor is sufficiently greater than outside the tumor to result in increased efficacy of the PARP inhibitor and topoisomerase inhibitor within the tumor, while reducing the peripheral toxicity of the combination therapy. The therapies disclosed herein are useful in the treatment of human cancers with solid tumors, including cervical cancer.

  提供了治疗癌症的组合疗法，包括给予拓扑异构酶-1抑制剂和PARP抑制剂。拓扑异构酶-1抑制剂可以脂质体制剂的形式给药，这种制剂能使拓扑异构酶-1抑制剂在肿瘤内相对于肿瘤外长时间蓄积。因此，通过在每次给药脂质体伊立替康制剂后延迟给药PARP抑制剂，直到拓扑异构酶抑制剂在肿瘤内的蓄积足够大于肿瘤外的蓄积，从而提高PARP抑制剂和拓扑异构酶抑制剂在肿瘤内的疗效，同时降低联合疗法的外周毒性，可以获得治疗益处。本文公开的疗法可用于治疗人类实体瘤癌症，包括宫颈癌。