NH2-Val-Ck-PABC-DOX | 1022094-34-3

• 分子结构分类: 有机化合物 - 苯丙烷和聚酮 - 蒽环类药物
• 英文名称: NH2-Val-Ck-PABC-DOX
• 英文别名: Val-Cit-PABC-DOX；[4-[[(2S)-2-[[(2S)-2-amino-3-methylbutanoyl]amino]-5-(carbamoylamino)pentanoyl]amino]phenyl]methyl N-[(2S,3S,4S,6R)-3-hydroxy-2-methyl-6-[[(1S,3S)-3,5,12-trihydroxy-3-(2-hydroxyacetyl)-10-methoxy-6,11-dioxo-2,4-dihydro-1H-tetracen-1-yl]oxy]oxan-4-yl]carbamate
• CAS: 1022094-34-3
• 化学式: C₄₆H₅₆N₆O₁₆
• 分子量: 948.981
• InChiKey: ULIDPLDJAHQACZ-MRCVXJENSA-N

物化性质

• 沸点：
  1198.9±65.0 °C(Predicted)
• 密度：
  1.50±0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  1.9
• 重原子数：
  68
• 可旋转键数：
  18
• 环数：
  6.0
• sp3杂化的碳原子比例：
  0.46
• 拓扑面积：
  358
• 氢给体数：
  11
• 氢受体数：
  17

反应信息

• 作为反应物：
  描述：

  NH2-Val-Ck-PABC-DOX 、 (2,5-Dioxopyrrolidin-1-yl) 3-[2-[2-[2-[2-[2-[2-[3-(2,5-dioxopyrrolidin-1-yl)-3-oxopropoxy]ethoxy]ethoxy]ethoxy]ethoxy]ethoxy]ethoxy]propanoate 在 N,N-二异丙基乙胺 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 反应 3.0h， 生成
  参考文献：
  名称：

  [EN] BIOLOGICAL MATERIALS AND USES THEREOF
  [FR] MATÉRIELS BIOLOGIQUES ET LEURS UTILISATIONS

  摘要：

  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。

  公开号：

  WO2016046574A1
• 作为产物：
  描述：

  在 四(三苯基膦)钯 、 三乙胺 、 三苯基硅烷 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 反应 2.0h， 生成 NH2-Val-Ck-PABC-DOX
  参考文献：
  名称：

  [EN] MODIFIED ANTIBODY, ANTIBODY-CONJUGATE AND PROCESS FOR THE PREPARATION THEREOF
  [FR] ANTICORPS MODIFIÉ, ANTICORPS-CONJUGUÉ ET PROCÉDÉ DE PRÉPARATION ASSOCIÉ

  摘要：

  本发明涉及一种包含GlcNAc-S(A)x取代基的抗体，其中S(A)x是一种包含x个功能基团A的糖衍生物，其中A是从包括偶氮基、酮基和炔基的组中独立选择的，x为1、2、3或4，其中所述的GlcNAc-S(A)x取代基通过所述的GlcNAc-S(A)x取代基的N-乙酰葡萄糖胺的CI与抗体结合，其中所述的N-乙酰葡萄糖胺可选择地被岩藻糖化。本发明还涉及一种抗体结合物，特别是根据式（20）或（20b）的抗体结合物，其中AB是一种抗体，S是一种糖或糖衍生物，D是一种感兴趣的分子，其中所述的N-乙酰葡萄糖胺可选择地被岩藻糖化（b为0或1）。本发明还涉及一种改性抗体的制备方法，一种抗体结合物的制备方法，以及用作药物的所述抗体结合物。此外，本发明还涉及一种部件套件，包括偶氮基修饰的抗体和连接物结合物，其中所述的连接物结合物包括（杂）环炔基团和一个或多个感兴趣的分子。

  公开号：

  WO2014065661A1

文献信息

• Antibody-conjugates with improved therapeutic index for targeting HER2 tumours and method for improving therapeutic index of antibody-conjugates
  申请人：SYNAFFIX B.V.

  公开号：US11338043B2

  公开（公告）日：2022-05-24

  The present invention concerns novel and improved antibody-conjugates for targeting HER2. The inventors found N that when antibody-conjugates were prepared using a specific mode of conjugation, they exhibit an improved therapeutic index. The mode of conjugation comprises a first step (i) of contacting a glycoprotein comprising 1-4 core N-acetylglucosamine moieties with a compound of the formula S(F1)x-P in the presence of a catalyst, wherein S(F1)x is a sugar derivative comprising x functional groups F1 capable of reacting with a functional group Q1, x is 1 or 2 and P is a nucleoside mono- or diphosphate, and wherein the catalyst is capable of transferring the S(F1)x moiety to the core-GlcNAc moiety, to obtain a modified antibody; and a second step (ii) of reacting the modified antibody with a linker-conjugate comprising a functional group Q1 capable of reacting with functional group F1 and a target molecule D connected to Q1 via a linker L2 to obtain the antibody-conjugate wherein linker L comprises S—Z3-L2 and wherein Z3 is a connecting group resulting from the reaction between Q1 and F1. The invention also relates to a use for improving the therapeutic index of an antibody-conjugate and to a method for targeting HER2-expressing cells.

  本发明涉及用于靶向 HER2 的新型改良抗体共轭物。发明者发现，当抗体结合物采用特定的结合模式制备时，它们的治疗指数会有所提高。共轭模式包括第一步(i)，在催化剂存在下，将包含 1-4 个核心 N-乙酰葡糖胺分子的糖蛋白与式 S(F1)x-P 的化合物接触、其中，S(F1)x 是包含 x 个官能团 F1 的糖衍生物，能与官能团 Q1 反应，x 是 1 或 2，P 是核苷单磷酸或二磷酸，催化剂能将 S(F1)x 基转移到核心-GlcNAc 基上，以获得修饰的抗体；第二步(ii)将修饰的抗体与连接体-共轭物反应，该连接体-共轭物包括能与官能团 F1 反应的官能团 Q1 和通过连接体 L2 与 Q1 连接的靶分子 D，从而得到抗体-共轭物，其中连接体 L 包括 S-Z3-L2，Z3 是 Q1 和 F1 反应产生的连接基团。本发明还涉及一种提高抗体轭合物治疗指数的用途和一种靶向 HER2 表达细胞的方法。
• [EN] EPSILON-POLY-L-LYSINE-BASED DRUG CONJUGATE, INTERMEDIATE THEREOF, AND APPLICATION THEREOF<br/>[FR] CONJUGUÉ DE MÉDICAMENT À BASE D'EPSILON-POLY-L-LYSINE, INTERMÉDIAIRE DE CELUI-CI, ET SON APPLICATION<br/>[ZH] 一种基于ε-聚-L-赖氨酸的药物偶联物、其中间体及其应用
  申请人：[en]SHANGHAI BEST-LINK BIOSCIENCE, LLC;[zh]上海弼领生物技术有限公司

  公开号：WO2023078464A1

  公开（公告）日：2023-05-11

  本发明公开了一种基于ε-聚-L-赖氨酸的药物偶联物、其中间体及其应用。本发明提供了一种如式(I)所示的具有基团偶联数量可控和基团偶联位点可控的ε-聚-L-赖氨酸衍生物-药物偶联物。本发明的药物偶联物具有肾脏清除率低、肝脾清除率低、血浆半衰期长、快速在病灶蓄积有效药物浓度和治疗效果更好的效果优势中的一个或多个。
• A cell-penetrating peptidic GRP78 ligand for tumor cell-specific prodrug therapy
  作者：Yoshiyuki Yoneda、Sebastian C.J. Steiniger、Kateřina Čapková、Jenny M. Mee、Ying Liu、Gunnar F. Kaufmann、Kim D. Janda

  DOI：10.1016/j.bmcl.2008.01.060

  日期：2008.3

  Tumor targeting peptides are promising vehicles for site-directed cancer therapy. Pep42, a cyclic 13-mer oligopeptide that specifically binds to glucose-regulated protein 78 (GRP78) and internalized into cancer cells, represents an excellent vehicle for tumor cell-specific chemotherapy. Here, we report the synthesis and evaluation of Pep42-prodrug conjugates that contain a cathepsin B-cleavable linker, resulting in the traceless release of drug inside the cancer cells. (c) 2008 Elsevier Ltd. All rights reserved.
• ANTIBODY-CONJUGATES WITH IMPROVED THERAPEUTIC INDEX FOR TARGETING HER2 TUMOURS AND METHOD FOR IMPROVING THERAPEUTIC INDEX OF ANTIBODY-CONJUGATES
  申请人：SYNAFFIX B.V.

  公开号：US20190262466A1

  公开（公告）日：2019-08-29

  The present invention concerns novel and improved antibody-conjugates for targeting HER2. The inventors found N that when antibody-conjugates were prepared using a specific mode of conjugation, they exhibit an improved therapeutic index. The mode of conjugation comprises a first step (i) of contacting a glycoprotein comprising 1-4 core N-acetylglucosamine moieties with a compound of the formula S(F 1 ) x -P in the presence of a catalyst, wherein S(F 1 ) x is a sugar derivative comprising x functional groups F1 capable of reacting with a functional group Q 1 , x is 1 or 2 and P is a nucleoside mono- or diphosphate, and wherein the catalyst is capable of transferring the S(F 1 ) x moiety to the core-GlcNAc moiety, to obtain a modified antibody; and a second step (ii) of reacting the modified antibody with a linker-conjugate comprising a functional group Q 1 capable of reacting with functional group F 1 and a target molecule D connected to Q 1 via a linker L 2 to obtain the antibody-conjugate wherein linker L comprises S—Z 3 -L 2 and wherein Z 3 is a connecting group resulting from the reaction between Q 1 and F 1 . The invention also relates to a use for improving the therapeutic index of an antibody-conjugate and to a method for targeting HER2-expressing cells.
• [EN] ANTIBODY-CONJUGATES WITH IMPROVED THERAPEUTIC INDEX FOR TARGETING CD30 TUMOURS AND METHOD FOR IMPROVING THERAPEUTIC INDEX OF ANTIBODY-CONJUGATES<br/>[FR] CONJUGUÉS D'ANTICORPS À INDICE THÉRAPEUTIQUE AMÉLIORÉ PERMETTANT DE CIBLER DES TUMEURS POSITIVES POUR LE CD30 ET MÉTHODE POUR AMÉLIORER L'INDICE THÉRAPEUTIQUE DE CONJUGUÉS D'ANTICORPS
  申请人：SYNAFFIX BV

  公开号：WO2017137457A1

  公开（公告）日：2017-08-17

  The present invention concerns novel and improved antibody-conjugates for targeting HER2. The inventors found that when antibody-conjugates were prepared using a specific mode of conjugation, they exhibit an improved therapeutic index. The mode of conjugation comprises a first step (i) of contacting a glycoprotein comprising 1 - 4 core N-acetylglucosamine moieties with a compound of the formula S(F1)x-P in the presence of a catalyst, wherein S(F1)x is a sugar derivative comprising x functional groups F1 capable of reacting with a functional group Q1, x is 1 or 2 and P is a nucleoside mono- or diphosphate, and wherein the catalyst is capable of transferring the S(F1)x moiety to the core-GlcNAc moiety, to obtain a modified antibody; and a second step (ii) of reacting the modified antibody with a linker-conjugate comprising a functional group Q1 capable of reacting with functional group F1 and a target molecule D connected to Q1 via a linker L2 to obtain the antibody-conjugate wherein linker L comprises S-Z3-L2 and wherein Z3 is a connecting group resulting from the reaction between Q1 and F1. The invention also relates to a use for improving the therapeutic index of an antibody-conjugate and to a method for targeting HER2-expressing cells.