(S)-2-((S)-2-(6-(2,5-dioxo-2,5-dihydro-1H-pyrrol-1-yl)-hexanamido)-3-methylbutanamido)propanoic acid | 1342820-51-2

• 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: (S)-2-((S)-2-(6-(2,5-dioxo-2,5-dihydro-1H-pyrrol-1-yl)-hexanamido)-3-methylbutanamido)propanoic acid
• 英文别名: 6-maleimidocaproyl-SGD-1910；Mc-Val-Ala-pbd；N-[(2S)-1-[[(2S)-1-[4-[(6aS)-3-[3-[[(6aS)-2-methoxy-8-(4-methoxyphenyl)-11-oxo-6a,7-dihydropyrrolo[2,1-c][1,4]benzodiazepin-3-yl]oxy]propoxy]-2-methoxy-11-oxo-6a,7-dihydropyrrolo[2,1-c][1,4]benzodiazepin-8-yl]anilino]-1-oxopropan-2-yl]amino]-3-methyl-1-oxobutan-2-yl]-6-(2,5-dioxopyrrol-1-yl)hexanamide
• CAS: 1342820-51-2
• 化学式: C₆₀H₆₄N₈O₁₂
• 分子量: 1089.21
• InChiKey: TWQIMWSQDICMSE-DGCIIGOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.5
• 重原子数：
  80
• 可旋转键数：
  23
• 环数：
  9.0
• sp3杂化的碳原子比例：
  0.35
• 拓扑面积：
  236
• 氢给体数：
  3
• 氢受体数：
  14

反应信息

• 作为产物：
  描述：

  SGD-1882 、 (6-(2,5-dioxo-2,5-dihydro-1H-pyrrol-1-yl)hexanoyl)-L-valyl-L-alanine 在 2-乙氧基-1-乙氧碳酰基-1,2-二氢喹啉 作用下， 以 甲醇 、 二氯甲烷 为溶剂， 反应 0.5h， 以45%的产率得到(S)-2-((S)-2-(6-(2,5-dioxo-2,5-dihydro-1H-pyrrol-1-yl)-hexanamido)-3-methylbutanamido)propanoic acid
  参考文献：
  名称：

  A Potent Anti-CD70 Antibody–Drug Conjugate Combining a Dimeric Pyrrolobenzodiazepine Drug with Site-Specific Conjugation Technology

  摘要：

  A highly cytotoxic DNA cross-linking pyrrolobenzodiazepine (PBD) dimer with a valine-alanine dipeptide linker was conjugated to the anti-CD70 h1F6 mAb either through endogenous interchain cysteines or, site-specifically, through engineered cysteines at position 239 of the heavy chains. The h1F6(239C)-PBD conjugation strategy proved to be superior to interchain cysteine conjugation, affording an antibody-drug conjugate (ADC) with high uniformity in drug-loading and low levels of aggregation. In vitro cytotoxicity experiments demonstrated that the h1F6(239C)-PBD was potent and immunologically specific on CD70-positive renal cell carcinoma (RCC) and non-Hodgkin lymphoma (NHL) cell lines. The conjugate was resistant to drug loss in plasma and in circulation, and had a pharmacokinetic profile closely matching that of the parental h1F6(239C) antibody capped with N-ethylmaleimide (NEM). Evaluation in CD70-positive RCC and NHL mouse xenograft models showed pronounced antitumor activities at single or weekly doses as low as 0.1 mg/kg of ADC. The ADC was tolerated at 2.5 mg/kg. These results demonstrate that PBDs can be effectively used for antibody-targeted therapy.

  DOI：

  10.1021/bc400217g

文献信息

• [EN] BIOLOGICAL MATERIALS AND USES THEREOF<br/>[FR] MATÉRIELS BIOLOGIQUES ET LEURS UTILISATIONS
  申请人：ANTIKOR BIOPHARMA LTD

  公开号：WO2016046574A1

  公开（公告）日：2016-03-31

  The invention provides compounds comprising a therapeutic agent coupled to a carrier molecule, with a minimum coupling ratio of 5: 1; wherein the carrier molecule is (i) an antibody fragment or derivative thereof or (ii) an antibody mimetic or derivative thereof; and wherein the therapeutic agents are coupled onto a lysine amino acid residue; and further wherein the therapeutic agent is not a photosensitising agent. There is also provided uses, methods relating to such compounds, as well as processes for their manufacture.

  该发明提供了包含治疗剂与载体分子偶联的化合物，最低偶联比为5:1；其中，载体分子是(i)抗体片段或其衍生物，或(ii)抗体模拟物或其衍生物；治疗剂偶联到赖氨酸氨基酸残基上；进一步，治疗剂不是光敏剂。还提供了关于这些化合物的用途、方法以及其制造过程。
• [EN] DIELS-ALDER CONJUGATION METHODS<br/>[FR] PROCÉDÉS DE CONJUGAISON DE DIELS-ALDER
  申请人：REGENERON PHARMA

  公开号：WO2021211984A1

  公开（公告）日：2021-10-21

  Described herein are protein-payload conjugates and compositions thereof that are useful, for example, for target-specific delivery of therapeutic and/or imaging agent moieties. In certain embodiments, provided are specific and efficient methods for producing protein-payload constructs (e.g., antibody-drug conjugates) utilizing a combination of transglutaminase and Diels-Alder techniques. Antibody-drug conjugates and compositions which comprise glutaminyl-modified antibodies, Diels-Alder adducts, and reactive payloads and are provided.

  本文描述了蛋白负载共轭物及其组合物，例如，用于靶向特定递送治疗和/或成像试剂团的。在某些实施例中，提供了利用转谷氨酰胺和Diels-Alder技术组合生产蛋白负载构建物（例如，抗体药物共轭物）的具体和高效方法。提供了包含谷氨酰修饰抗体、Diels-Alder加合物和反应性载体的抗体-药物共轭物和组合物。
• TARGETED PYRROLOBENZODIAZAPINE CONJUGATES
  申请人：Howard Philip Wilson

  公开号：US20130028919A1

  公开（公告）日：2013-01-31

  Provided are Conjugate comprising PBDs conjugated to a targeting agent and methods of using such PBDs.

  提供了一种包含PBDs与靶向剂结合的共轭物，并提供了使用这种PBDs的方法。
• ACTIVATED CARBON FILTRATION FOR PURIFICATION OF BENZODIAZEPINE ADCS
  申请人：Seattle Genetics, Inc.

  公开号：EP3441072A1

  公开（公告）日：2019-02-13

  Disclosed are methods of purifying mixtures comprising benzodiazepine antibody-drug conjugates.

  所公开的是纯化包含苯并二氮杂卓抗体-药物共轭物的混合物的方法。
• ANTI-CMET ANTIBODY DRUG CONJUGATES AND METHODS FOR THEIR USE
  申请人：AbbVie Biotherapeutics Inc.

  公开号：EP3804765A1

  公开（公告）日：2021-04-14

  The present disclosure provides antibody drug conjugates that bind human cMET, their methods of making, and their uses to treat patients having cancer.

  本公开提供了与人类 cMET 结合的抗体药物结合物、其制造方法及其用于治疗癌症患者的用途。