{"entity":{"id":"topoisomerase-i-payloads","kind":"term","name":"Topoisomerase-I inhibitor payloads","aka":["camptothecin payloads","TOP1 payloads"],"tldr":"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.","asOf":"2026-09-09","wikipedia":"https://en.wikipedia.org/wiki/Camptothecin","links":[{"label":"Wikipedia","url":"https://en.wikipedia.org/wiki/Camptothecin"}],"tags":[],"related":["topoisomerase-inhibitors","adc-sequencing","efflux-pump","bystander-effect"],"cancers":[],"sections":[],"technologies":["adc"],"targets":[],"drugs":["sacituzumab-govitecan","trastuzumab-deruxtecan","datopotamab-deruxtecan","patritumab-deruxtecan","ifinatamab-deruxtecan","raludotatug-deruxtecan","izalontamab-brengitecan","tilatamig-samrotecan","ak146d1","puxitatug-samrotecan","sacituzumab-tirumotecan"],"companies":[],"institutions":[],"pathways":[],"terms":["payload"],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"category":"ADC chemistry"},"route":"/terms/topoisomerase-i-payloads/","neighbours":{"technology":[{"id":"adc","kind":"technology","name":"Antibody-drug conjugate (ADC)","route":"/technologies/adc/"},{"id":"topoisomerase-inhibitors","kind":"technology","name":"Topoisomerase-I inhibitors (and ADC payloads)","route":"/technologies/topoisomerase-inhibitors/"}],"term":[{"id":"adc-sequencing","kind":"term","name":"ADC sequencing","route":"/terms/adc-sequencing/"},{"id":"bystander-effect","kind":"term","name":"Bystander effect (ADC)","route":"/terms/bystander-effect/"},{"id":"efflux-pump","kind":"term","name":"Drug efflux pumps (ABC transporters)","route":"/terms/efflux-pump/"},{"id":"dxd","kind":"term","name":"DXd","route":"/terms/dxd/"},{"id":"exatecan","kind":"term","name":"Exatecan (and derivatives)","route":"/terms/exatecan/"},{"id":"payload","kind":"term","name":"Payload (ADC)","route":"/terms/payload/"},{"id":"sn-38","kind":"term","name":"SN-38","route":"/terms/sn-38/"},{"id":"t030","kind":"term","name":"T030 (belotecan derivative)","route":"/terms/t030/"}],"drug":[{"id":"ak146d1","kind":"drug","name":"AK146D1","route":"/drugs/ak146d1/"},{"id":"datopotamab-deruxtecan","kind":"drug","name":"Datopotamab deruxtecan","route":"/drugs/datopotamab-deruxtecan/"},{"id":"ifinatamab-deruxtecan","kind":"drug","name":"Ifinatamab deruxtecan","route":"/drugs/ifinatamab-deruxtecan/"},{"id":"izalontamab-brengitecan","kind":"drug","name":"Izalontamab brengitecan","route":"/drugs/izalontamab-brengitecan/"},{"id":"patritumab-deruxtecan","kind":"drug","name":"Patritumab deruxtecan","route":"/drugs/patritumab-deruxtecan/"},{"id":"puxitatug-samrotecan","kind":"drug","name":"Puxitatug samrotecan","route":"/drugs/puxitatug-samrotecan/"},{"id":"raludotatug-deruxtecan","kind":"drug","name":"Raludotatug deruxtecan","route":"/drugs/raludotatug-deruxtecan/"},{"id":"sacituzumab-govitecan","kind":"drug","name":"Sacituzumab govitecan","route":"/drugs/sacituzumab-govitecan/"},{"id":"sacituzumab-tirumotecan","kind":"drug","name":"Sacituzumab tirumotecan","route":"/drugs/sacituzumab-tirumotecan/"},{"id":"tilatamig-samrotecan","kind":"drug","name":"Tilatamig samrotecan","route":"/drugs/tilatamig-samrotecan/"},{"id":"trastuzumab-deruxtecan","kind":"drug","name":"Trastuzumab deruxtecan","route":"/drugs/trastuzumab-deruxtecan/"}],"pathway":[{"id":"dna-replication-licensing","kind":"pathway","name":"DNA replication & origin licensing","route":"/pathways/dna-replication-licensing/"}]}}