Calicheamicin
Description
Calicheamicin, an enediyne antibiotic with extreme cytotoxicity, is a validated payload in antibody-drug conjugates (ADCs). The preclinical evaluation of ABBV-011, an SEZ6-targeted calicheamicin ADC, focused on experimental characterization of catabolic stability. Researchers employed in vitro plasma incubation assays combined with HPLC-MS analytical profiling to identify circulating metabolites and catabolites. Comparative metabolic studies against gemtuzumab ozogamicin and inotuzumab ozogamicin revealed a novel liability: disulfide bond cleavage in the N-acetyl-γ-calicheamicin payload, compromising linker stability. This was further supported by in vivo pharmacokinetic experiments, which confirmed similar degradation pathways. These experimental insights emphasize the importance of systWeb page:
