calicheamicin

Calicheamicin is a highly potent **enediyne antitumor antibiotic** originally derived from the soil bacterium *Micromonospora echinospora*. It acts by binding to DNA in the minor groove and undergoes a reaction (Bergman cyclization) to generate a highly reactive diradical intermediate that abstracts hydrogen atoms from the DNA backbone, leading to **double-strand DNA breaks and cell death at extremely low concentrations**[1][8]. As an isolated agent, calicheamicin is too toxic and has a narrow therapeutic window for clinical use, but it is effectively used as the cytotoxic payload in several approved antibody-drug conjugates (ADCs), such as gemtuzumab ozogamicin and inotuzumab ozogamicin[1][5][7]. Calicheamicin–antibody conjugates harness the cytotoxicity of calicheamicin while targeting specific cell surface antigens, improving selectivity and therapeutic index[5]. The core structure features an enediyne ring, which is key to its DNA-damaging mechanism[1][3].

Other names

enediyne antibioticcalicheamicin gamma1calicheamicin gamma(1,I)