Natural products as a source of cytotoxic warheads in antibody-drug conjugates

Antibody-drug conjugates (ADCs) are one of the most rapidly expanding classes of oncology therapeutics. Till now, 11 ADCs have been approved by USFDA, with the first ADC approval of gemtuzumab ozogamicin (Mylotarg) in 2000. A large number of ADCs are being evaluated in different stages of clinical t...

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Bibliographic Details
Published inNatural product research Vol. 37; no. 17; pp. 2973 - 2985
Main Authors Goel, Bharat, Jain, Shreyans K.
Format Journal Article
LanguageEnglish
Published Abingdon Taylor & Francis 02.09.2023
Taylor & Francis Ltd
Subjects
ADCs
Antibodies
Antibody-drug conjugates
Calicheamicin
Camptothecin
Cancer
Clinical trials
Conjugates
cytotoxic warheads
Cytotoxicity
Gemtuzumab ozogamicin
Natural products
Warheads
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Summary:Antibody-drug conjugates (ADCs) are one of the most rapidly expanding classes of oncology therapeutics. Till now, 11 ADCs have been approved by USFDA, with the first ADC approval of gemtuzumab ozogamicin (Mylotarg) in 2000. A large number of ADCs are being evaluated in different stages of clinical trials and pre-clinical studies. Interestingly, the cytotoxic warheads of the all approved ADCs, as well as clinical and preclinical candidates, belong to different classes of natural products viz. calicheamicins, auristatins, maytansinoids, camptothecin derivatives, pyrolidobenzodiazepines (PBDs), and duocarmycins, etc. Herein, a review of the natural product-based cytotoxic warheads, briefly discussing their source, modifications, and mechanism of action, has been conducted.
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ISSN:1478-6419
1478-6427
DOI:10.1080/14786419.2022.2138872