BioCentury
ARTICLE | Distillery Techniques

Techniques: Stable antibody-drug conjugates (ADCs) based on pyridazinedione linkers

May 21, 2015 7:00 AM UTC

Pyridazinedione-based linkers could produce more stable ADCs than linkers based on modified lysines or thiols. Dibromopyridazinedione readily inserted itself into the native disulfide bridges between antibody heavy and light chains, leaving each nitrogen on the linker available for drug conjugation via click chemistry. In human breast cancer cell lines, an ADC of Herceptin trastuzumab and the generic chemotherapeutic doxorubicin linked by pyridazinedione was internalized by and induced death in epidermal growth factor receptor 2 (HER2; EGFR2; ErbB2; neu)-positive cells but not in HER2-negative cells. Next steps include in vivo characterization of the ADCs...