monomethyl auristatin F trifluoroacetate | 1608127-41-8

• 分子结构分类: 有机化合物 - 有机酸及其衍生物 - 肽模拟物
• 英文名称: monomethyl auristatin F trifluoroacetate
• 英文别名: MMAF*TFA
• CAS: 1608127-41-8
• 化学式: C₂HF₃O₂*C₃₉H₆₅N₅O₈
• 分子量: 845.998
• InChiKey: CWWQUPAUNVWYQB-KMYLZLQDSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.74
• 重原子数：
  59.0
• 可旋转键数：
  21.0
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.71
• 拓扑面积：
  203.91
• 氢给体数：
  5.0
• 氢受体数：
  9.0

反应信息

• 作为反应物：
  描述：

  monomethyl auristatin F trifluoroacetate 、 丙炔基-三聚乙二醇-乙酸 在 N,N-二异丙基乙胺 、 N-[(dimethylamino)-3-oxo-1H-1,2,3-triazolo[4,5-b]pyridin-1-yl-methylene]-N-methylmethanaminium hexafluorophosphate 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 反应 1.17h， 以65%的产率得到
  参考文献：
  名称：

  [EN] ANTIBODY COMPOUNDS WITH REACTIVE ARGININE AND RELATED ANTIBODY DRUG CONJUGATES
  [FR] COMPOSÉS D'ANTICORPS AVEC ARGININE RÉACTIVE ET CONJUGUÉS ANTICORPS-MÉDICAMENT ASSOCIÉS

  摘要：

  本发明提供了含有在疏水裂缝（38C2_Arg）中对活性赖氨酸残基（Lys99）进行氨基酸替换的抗体化合物。该发明还提供了含有货基团的抗体药物结合物（ADCs），这些货基团被特异性地共轭到38C2_Arg变体抗体中的工程氨基酸残基上。该发明还提供了这些化合物的治疗应用。

  公开号：

  WO2020076849A1

文献信息

• [EN] LINKERS FOR ANTIBODY DRUG CONJUGATES<br/>[FR] LIEURS POUR CONJUGUÉS ANTICORPS-MÉDICAMENT
  申请人：UNIV TEXAS

  公开号：WO2018218004A1

  公开（公告）日：2018-11-29

  In one aspect, the present disclosure provides compounds of the formula (I): wherein the variables are as defined herein. In another aspect, the present disclosure provides compounds of the formula (V): wherein the variables are as defined herein. In another aspect, the present disclosure also provides methods of preparing the compounds disclosed herein. In another aspect, the present disclosure provides antibody drug conjugates comprising compounds of the present disclosure. In another aspect, the present disclosure also provides pharmaceutical compositions and methods of use of the compounds and anti-body drug conjugates disclosed herein.

  一方面，本公开提供了通式(I)的化合物：其中变量如本文所定义。另一方面，本公开提供了通式(V)的化合物：其中变量如本文所定义。另一方面，本公开还提供了制备本文所述化合物的方法。另一方面，本公开提供了包含本公开化合物的抗体药物偶联物。另一方面，本公开还提供了本文所述化合物和抗体药物偶联物的药物组合物及其使用方法。
• [EN] MODIFIED ANTIBODY, ANTIBODY-CONJUGATE AND PROCESS FOR THE PREPARATION THEREOF<br/>[FR] ANTICORPS MODIFIÉ, ANTICORPS-CONJUGUÉ ET PROCÉDÉ DE PRÉPARATION ASSOCIÉ
  申请人：SYNAFFIX BV

  公开号：WO2014065661A1

  公开（公告）日：2014-05-01

  The present invention relates to an antibody comprising a GlcNAc-S(A)x substituent, wherein S(A)x is a sugar derivative comprising x functional groups A wherein A is independently selected from the group consisting of an azido group, a keto group and an alkynyl group and x is 1, 2, 3 or 4, wherein said GlcNAc-S(A)x substituent is bonded to the antibody via CI of the N-acetylglucosamine of said GlcNAc-S(A)x substituent, and wherein said N-acetylglucosamine is optionally fucosylated. The invention also relates to an antibody-conjugate, in particular to an antibody- conjugate according to the Formula (20) or (20b), wherein AB is an antibody, S is a sugar or a sugar derivative, D is a molecule of interest, and wherein said N- acetylglucosamine is optionally fucosylated (b is 0 or 1). The invention further relates to a process for the preparation of a modified antibody, to a process for the preparation of an antibody-conjugate, and to said antibody-conjugate for use as a medicament. In addition, the invention relates to a kit of parts comprising an azide-modified antibody and a linker-conjugate, wherein said linker-conjugate comprises a (hetero)cycloalkynyl group and one or more molecules of interest.

  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。
• Synthesis and Biological Evaluation of RGD and <i>iso</i> DGR–Monomethyl Auristatin Conjugates Targeting Integrin α _V β ₃
  作者：André Raposo Moreira Dias、Lizeth Bodero、Ana Martins、Daniela Arosio、Silvia Gazzola、Laura Belvisi、Luca Pignataro、Christian Steinkühler、Alberto Dal Corso、Cesare Gennari、Umberto Piarulli

  DOI：10.1002/cmdc.201900049

  日期：2019.5.6

  the key step. The conjugates were tested for their binding affinity for the isolated αv β3 receptor and were shown to retain nanomolar IC50 values, in the same range as those of the free ligands. The cytotoxic activity of the conjugates was evaluated in cell viability assays with αv β3 integrin overexpressing human glioblastoma (U87) and human melanoma (M21) cells. The conjugates possess markedly lower

  这项工作报告了一系列的小分子药物偶联物的合成，这些偶联物包含αVβ3-整联蛋白配体环[DKP-RGD]或环[DKP-isoDGR]，溶酶体可裂解的Val-Ala（VA）接头或“不可裂解的”没有该序列的版本，并且单甲基澳瑞他汀E（MMAE）或F（MMAF）作为细胞毒剂。结合物是通过简单的合成方案获得的，利用铜催化的叠氮化物-炔烃环加成反应为关键步骤。测试缀合物对分离的αvβ3受体的结合亲和力，并显示其保留的纳摩尔IC50值在与游离配体相同的范围内。用过表达人成胶质细胞瘤（U87）和人黑素瘤（M21）细胞的αvβ3整联蛋白的细胞生存力分析评估了缀合物的细胞毒活性。结合物比游离药物具有明显更低的细胞毒性活性，这与整合素介导的内在化效率低下是一致的。在几乎所有情况下，以isoDGR为整联蛋白配体的缀合物均比其RGD对应物表现出更高的效价。特别是，环[DKP-isoDGR] -VA-MMAE缀合物在
• Site-Selective Antibody Functionalization via Orthogonally Reactive Arginine and Lysine Residues
  作者：Dobeen Hwang、Napon Nilchan、Alex R. Nanna、Xiaohai Li、Michael D. Cameron、William R. Roush、HaJeung Park、Christoph Rader

  DOI：10.1016/j.chembiol.2019.05.010

  日期：2019.9

  Homogeneous antibody-drug conjugates (ADCs) that use a highly reactive buried lysine (Lys) residue embedded in a dual variable domain (DVD)-IgG1 format can be assembled with high precision and efficiency under mild conditions. Here we show that replacing the Lys with an arginine (Arg) residue affords an orthogonal ADC assembly that is site-selective and stable. X-ray crystallography confirmed the location of the reactive Arg residue at the bottom of a deep pocket. As the Lys-to-Arg mutation is confined to a single residue in the heavy chain of the DVD-IgG1, heterodimeric assemblies that combine a buried Lys in one arm, a buried Arg in the other arm, and identical light chains, are readily assembled. Furthermore, the orthogonal conjugation chemistry enables the loading of heterodimeric DVD-IgG1s with two different cargos in a one-pot reaction and thus affords a convenient platform for dual-warhead ADCs and other multifaceted antibody conjugates.
• [EN] CONJUGATES COMPRISING A PHOSPHORUS (V) AND A DRUG MOIETY<br/>[FR] CONJUGUÉS COMPRENANT UN PHOSPHORE (V) ET UNE FRACTION DE MÉDICAMENT
  申请人：[en]TUBULIS GMBH

  公开号：WO2023083900A1

  公开（公告）日：2023-05-19

  The present invention relates to a conjugate having the formula (I): wherein a receptor binding molecule (RBM) is connected with a drug moiety (D). The present invention also relates to intermediates for producing the same, methods of preparing the same, pharmaceutical compositions comprising the same, as well as uses thereof.