Antibody drug conjugates of echinomycin-based payloads

Antibody drug conjugates (ADCs) based on the natural product echinomycin have been developed. By replacing unique and synthetically challenging functionality along with sidechain modifications and quinoxaline functionality, a variety of potent cytotoxic derivatives were discovered. The authors in this report employed the well-studied HER2 model system along with a MDR cell line to probe for drug resistance. The research resulted in potent quinoline/quinoxaline-based payloads that were further elaborated with linkers for conjugating to antibodies. Targeting and non-targeting ADCs yielded potent and selective conjugates.