# Topoisomerase-I inhibitor payloads

Source: https://onco.cc/terms/topoisomerase-i-payloads/  
OnCo record `topoisomerase-i-payloads` (Term). Data CC BY-NC 4.0, attribute "Data from OnCo (onco.cc)"; commercial use needs a licence.

## TL;DR

Topoisomerase-I inhibitor payloads are the payload class behind Enhertu, Trodelvy and Dato-DXd: poisons that trap the enzyme that untwists DNA, so dividing cells break their own DNA.

## Summary

Camptothecin derivatives (SN-38, DXd, exatecan and its children, T030) stabilise topoisomerase I on DNA. They are membrane permeable, so most give a bystander effect, and they tolerate high drug-to-antibody ratios. The class shares resistance routes: TOP1 mutations, loss of SLFN11 and efflux pumps, which is why a second topoisomerase-I ADC after the first fails is often disappointing. Interstitial lung disease, neutropenia and diarrhoea are class toxicities that differ in weight between members.

## Fields

- Kind: Term
- Last checked: 2026-09-09
- Also known as: camptothecin payloads; TOP1 payloads

## Sources

- Wikipedia: https://en.wikipedia.org/wiki/Camptothecin
- Wikipedia: https://en.wikipedia.org/wiki/Camptothecin

## Connected records

- technologies: [Antibody-drug conjugate (ADC)](https://onco.cc/technologies/adc/), [Topoisomerase-I inhibitors (and ADC payloads)](https://onco.cc/technologies/topoisomerase-inhibitors/)
- terms: [ADC sequencing](https://onco.cc/terms/adc-sequencing/), [Bystander effect (ADC)](https://onco.cc/terms/bystander-effect/), [Drug efflux pumps (ABC transporters)](https://onco.cc/terms/efflux-pump/), [DXd](https://onco.cc/terms/dxd/), [Exatecan (and derivatives)](https://onco.cc/terms/exatecan/), [Payload (ADC)](https://onco.cc/terms/payload/), [SN-38](https://onco.cc/terms/sn-38/), [T030 (belotecan derivative)](https://onco.cc/terms/t030/)
- drugs: [AK146D1](https://onco.cc/drugs/ak146d1/), [Datopotamab deruxtecan](https://onco.cc/drugs/datopotamab-deruxtecan/), [Ifinatamab deruxtecan](https://onco.cc/drugs/ifinatamab-deruxtecan/), [Izalontamab brengitecan](https://onco.cc/drugs/izalontamab-brengitecan/), [Patritumab deruxtecan](https://onco.cc/drugs/patritumab-deruxtecan/), [Puxitatug samrotecan](https://onco.cc/drugs/puxitatug-samrotecan/), [Raludotatug deruxtecan](https://onco.cc/drugs/raludotatug-deruxtecan/), [Sacituzumab govitecan](https://onco.cc/drugs/sacituzumab-govitecan/), [Sacituzumab tirumotecan](https://onco.cc/drugs/sacituzumab-tirumotecan/), [Tilatamig samrotecan](https://onco.cc/drugs/tilatamig-samrotecan/), [Trastuzumab deruxtecan](https://onco.cc/drugs/trastuzumab-deruxtecan/)
- pathways: [DNA replication & origin licensing](https://onco.cc/pathways/dna-replication-licensing/)

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