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termsTerm

Calicheamicin

aka ozogamicin payload, N-acetyl gamma calicheamicin, ozogamicin (N-acetyl-γ-calicheamicin)

Calicheamicin is a DNA-cutting natural product carried by Mylotarg and Besponsa. It is powerful, but liver toxicity limits it.

Calicheamicin binds the minor groove and, once its enediyne core rearranges, cuts both strands of DNA. It is released by an acid-cleavable hydrazone linker in the lysosome. Gemtuzumab ozogamicin (CD33, acute myeloid leukaemia) and inotuzumab ozogamicin (CD22, acute lymphoblastic leukaemia) carry it. Hepatotoxicity, including veno-occlusive disease especially around stem-cell transplant, is the characteristic risk.

Category
ADC chemistry

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