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

Abstract

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.

Graphical Abstract

Keywords:

• Antibody-drug conjugates
• ADCs
• natural products
• cytotoxic warheads
• Cancer

Acknowledgment

Bharat Goel is thankful to Professor Monica Gulati, Lovely Professional University, Punjab, for providing the necessary facilities to complete this work.

Disclosure statement

No potential conflict of interest was reported by the authors.

Funding

The author(s) reported there is no funding associated with the work featured in this article.