布鲁顿酪氨酸激酶
体内
抗体-药物偶联物
酪氨酸激酶
小脑
单克隆抗体
体外
药理学
连接器
化学
半抗原
癌症研究
抗体
医学
泛素连接酶
生物
免疫学
生物化学
信号转导
计算机科学
生物技术
泛素
操作系统
基因
作者
Alan Zhang,Katherine Seiss,Sebastian Palacio-Ramirez,Laurent Laborde,Daniel Guthy,Mylene Lanter,John Lorber,Anna Vulpetti,Thomas Zöller,Christina Hebach,William R. Tschantz,Alexei S. Karpov,Gregory J. Hollingworth,Joseph A. D’Alessio,Stéphane Ferretti,Matthew T. Burger
标识
DOI:10.26434/chemrxiv-2023-1d5qx
摘要
Antibody-drug conjugates (ADCs) are an established modality which allows for targeted delivery of a potent molecule, or payload, to a desired site of action. ADCs, wherein the payload is a targeted protein degrader is an emerging area in the field. Herein we describe our efforts of delivering a Bruton’s tyrosine kinase (BTK) bifunctional degrader 1 via a CD79b mAb where the degrader is linked at the ligase binding portion of the payload via a cleavable linker to the mAb. The resulting CD79b ADCs, 3 and 4, exhibit in vitro degradation and cytotoxicity comparable to 1 and ADC 3 can achieve more sustained in vivo degradation than iv administered 1 with markedly reduced systemic exposure of the payload.
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