The calicheamicins are potent DNA-damaging agents that are capable of promoting double-strand DNA breaks and are ideal antibody drug conjugate (ADC) payloads. Harnessing the reactivity of these natural products has been critical for the design and development of calicheamicin-based ADCs. The structural complexity poses a significant challenge to understanding the chemistry of these molecules. For the development of next generation calicheamicin ADCs, our work has focused on refining the linker chemistry and the method and site of conjugation, as well as understanding the reactivity and SAR of the payload itself, with the goals of improving efflux, efficacy and more importantly, selectivity. These modifications led to a more efficacious and safer conjugate that overcame hepatotoxicity observed with first and second generation calicheamicin ADCs.

Development of next generation calicheamicin ADCs

ACS Spring 2022

The official archive and repository for all ACS Meetings & Expositions abstracts and select posters or presentations.