Christopher J. O’Donnell

TL;DR: It is shown that the conjugation site has significant impact on ADC stability and pharmacokinetics in a species-dependent manner and can be directly attributed to the position of the linkage rather than the chemical instability, as was observed with a maleimide linkage.

TL;DR: This work presents a compelling case for its broader application as a phenyl group replacement in scenarios where the aromatic ring count impacts physicochemical parameters and overall drug-likeness.

TL;DR: In this article, a trastuzumab-maytansinoid ADC (TM-ADC) was applied to breast cancer cell lines, and the authors found that the ADC-resistant cells, 361-TM and JIMT1-TM, were characterized by cytotoxicity, proteomic, transcriptional and other profiling.

TL;DR: Cboxylesterase 1C is identified as the enzyme responsible for the extracellular hydrolysis of valine-citrulline-p-aminocarbamate (VC-PABC)-based linkers in mouse plasma and modulated by small chemical modifications to the linker shows the opportunity to modulate the extacellular stability of cleavable ADCs without diminishing the intracellular payload release required for ADC efficacy.

TL;DR: A systematic approach to translating standard organic reactions to a DEL setting through the tactical combination of kinetic analysis and empirical screening with information captured from data mining is described.