Payload cytotoxic target

The term "Payload cytotoxic target" refers to the specific intracellular molecule or biological structure that a cytotoxic drug (the payload) interacts with to exert its lethal effect within a target cell (NCI Thesaurus, 2024). In the context of Antibody-Drug Conjugates (ADCs), while the antibody component targets a cell-surface antigen, the payload is designed to hit a "payload cytotoxic target" once internalized and released (Nature Reviews Drug Discovery, 2021). The most common targets include tubulin, which is disrupted by antimitotic agents like auristatins and maytansinoids, and DNA or DNA-associated enzymes like Topoisomerase I, which are targeted by DNA-damaging agents or camptothecin derivatives (PubMed, PMID: 32814024). The choice of payload cytotoxic target is a critical factor in ADC design, influencing the drug's potency, its ability to kill non-dividing cells, and its potential for "bystander killing" of adjacent tumor cells (ADC Review, 2023). Understanding these targets is essential for managing the systemic toxicities often associated with the premature release of the payload in circulation (StatPearls, 2024).

Other names

Intracellular payload targetADC payload targetCytotoxic mechanism targetPayload target

Inhibition of microtubule assembly, inhibition of DNA topoisomerase I, DNA alkylation, or DNA strand scission.