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

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

  • Antib Ther. 2021 Jan;4(1):1-15. doi: 10.1093/abt/tbab001.
Ajeeth Adhikari 1 2,  Ben Shen 1 3 4,  Christoph Rader 2
Affiliations

Affiliations

  • 1 Department of Chemistry, The Scripps Research Institute, Jupiter, FL, USA.
  • 2 Department of Immunology and Microbiology, The Scripps Research Institute, Jupiter, FL, USA.
  • 3 Department of Molecular Medicine, The Scripps Research Institute, Jupiter, FL, USA.
  • 4 Natural Products Discovery Center at Scripps Research, The Scripps Research Institute, Jupiter, FL, USA.
PMID: 33554043 DOI: 10.1093/abt/tbab001
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.

Keywords

anthraquinone-fused enediynes; antibody-drug conjugates; enediyne natural products; gemtuzumab ozogamicin; inotuzumab ozogamicin; payloads.

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