Data from Development of Novel Quaternary Ammonium Linkers for Antibody–Drug Conjugates

• DOI: 10.1158/1535-7163.c.6538699.v1
• Publication Date: 2023-04-03T20:48:10Z
• Authors: Patrick J. Burke; Joseph Z. Hamilton; Thomas A. Pires; Jocelyn R. Setter; Joshua H. Hunter; Julia H. Cochran; Andrew B. Waight; Kristine A. Gordon; Brian E. Toki; Kim K. Emmerton; Weiping Zeng; Ivan J. Stone; Peter D. Senter; Robert P. Lyon; Scott C. Jeffrey
• Keywords: Linker; Conjugate; Glucuronide

<div>Abstract<p>A quaternary ammonium-based drug-linker has been developed to expand the scope of antibody–drug conjugate (ADC) payloads include tertiary amines, a functional group commonly present in biologically active compounds. The linker strategy was exemplified with β-glucuronidase–cleavable auristatin E construct. found efficiently release free (AE) presence β-glucuronidase and provide ADCs that were highly stable plasma. Anti-CD30 conjugates comprised glucuronide-AE potent immunologically specific <i>in vitro</i> vivo</i>, displaying pharmacologic properties comparable carbamate-linked glucuronide-monomethylauristatin control. ammonium then applied tubulysin antimitotic drug contained an N-terminal amine important for activity. A glucuronide-tubulysin synthesized evaluated as ADC payload, which resulting be vitro</i>, displayed high level activity Hodgkin lymphoma xenograft. Furthermore, results superior those obtained related derivative containing secondary N-terminus conjugation using previously known technology. represents significant advance technology, enabling residues. <i>Mol Cancer Ther; 15(5); 938–45. ©2016 AACR</i>.</p></div>