化学
结合
连接器
体外
药品
酶
有效载荷(计算)
抗体-药物偶联物
单克隆抗体
部分
生物化学
组合化学
抗体
药理学
立体化学
免疫学
医学
数学分析
计算机网络
数学
网络数据包
计算机科学
生物
操作系统
作者
Andrew J. Bessire,T. Eric Ballard,Manoj B. Charati,Justin D. Cohen,Michael Green,My‐Hanh Lam,Frank Loganzo,Birte Nolting,Betsy S. Pierce,Sujiet Puthenveetil,Lee R. Roberts,Klaas Schildknegt,Chakrapani Subramanyam
标识
DOI:10.1021/acs.bioconjchem.6b00192
摘要
Antibody-drug conjugates (ADC) are currently an active area of research, focused primarily on oncology therapeutics, but also to a limited extent on other areas such as infectious disease. The success of this type of targeted drug delivery is dependent upon many factors, one of which is the performance of the linker in releasing an active drug moiety under the appropriate conditions. As a tool in the development of linker/payload chemistry, we have developed an in vitro method for the identification of payload species released from ADCs in the presence of lysosomal enzymes. This method utilizes commercially available human liver S9 fraction as the source of these enzymes, and this has certain advantages over lysosomal fractions or purified enzymes. This article describes the characterization and performance of this assay with multiple ADCs composed of known and novel linkers and payloads. Additionally, we report the observation of incomplete degradation of mAb protein chains by lysosomal enzymes in vitro, believed to be the first report of this phenomenon involving an ADC therapeutic.
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