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Challenges and Opportunities to Develop Enediyne Natural Products as Payloads for Antibody-Drug Conjugates.

ABSTRACT: Calicheamicin, the payload of the antibody-drug-conjugates (ADCs) gemtuzumab ozogamicin (Mylotarg^®) and inotuzumab ozogamicin (Besponsa^®), belongs to the class of enediyne natural products. Since the isolation and structural determination of the neocarzinostatin chromophore in 1985, the enediynes have attracted considerable attention for their value as DNA damaging agents in cancer chemotherapy. Due to their non-discriminatory cytotoxicity towards both cancer and healthy cells, the clinical utilization of enediyne natural products relies on conjugation to an appropriate delivery system, such as an antibody. Here we review the current landscape of enediynes as payloads of first-generation and next-generation ADCs.

SUBMITTER: Adhikari A

PROVIDER: S-EPMC7850032 | biostudies-literature | 2021 Jan

REPOSITORIES: biostudies-literature

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Challenges and Opportunities to Develop Enediyne Natural Products as Payloads for Antibody-Drug Conjugates.

Adhikari Ajeeth A Shen Ben B Rader Christoph C

Antibody therapeutics 20210112 1

Calicheamicin, the payload of the antibody-drug-conjugates (ADCs) gemtuzumab ozogamicin (Mylotarg<sup>®</sup>) and inotuzumab ozogamicin (Besponsa<sup>®</sup>), belongs to the class of enediyne natural products. Since the isolation and structural determination of the neocarzinostatin chromophore in 1985, the enediynes have attracted considerable attention for their value as DNA damaging agents in cancer chemotherapy. Due to their non-discriminatory cytotoxicity towards both cancer and healthy ce ...[more]

PMID: 33554043

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