Merck

Last updated January 31, 2026

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Exatecan-derived topoisomerase-1 inhibitor payloads: MerckRecent Research Landscape

Off-target toxicity and poor linker stability in antibody-drug conjugates lead to systemic side effects and reduced efficacy. These innovations engineer specific chemical modifications to exatecan and anthracycline structures to optimize payload potency and conjugation stability.

What technical problems is Merck addressing in Exatecan-derived topoisomerase-1 inhibitor payloads?

Insufficient tumor cell selectivity

(10)evidences

Low systemic stability and poor target selectivity limit the maximum tolerated dose of cytotoxic payloads. Improving the therapeutic index allows for higher efficacy with reduced off-target toxicity.

Off-target intestinal toxicity

(9)evidences

Narrow safety margins and systemic toxicity limit the clinical utility of camptothecin analogs. Improving the therapeutic index allows for higher localized efficacy without prohibitive off-target damage.