{"entity":{"id":"exatecan","kind":"term","name":"Exatecan (and derivatives)","aka":["DX-8951","Ed-04","ZD06519","DX-8951; Ed-04 in iza-bren; ZD06519"],"tldr":"Exatecan is a camptothecin that blocks topoisomerase I; it was too toxic to use as a free chemotherapy, but attached to an antibody that toxicity becomes useful, and it is the parent of deruxtecan and most next-generation ADC payloads. The family shares resistance mechanisms, so switching between exatecan ADCs after progression often disappoints.","summary":"Exatecan (DX-8951) failed as a standalone chemotherapy because it was too toxic, but attached to an antibody its potency becomes an advantage. Deruxtecan, Ed-04 (izalontamab brengitecan), ZD06519 (Zymeworks) and other derivatives tune solubility, release and bystander behaviour. The class shares topoisomerase-I resistance mechanisms (TOP1 mutations, SLFN11 loss, efflux), so switching between exatecan-family ADCs after progression often disappoints.","asOf":"2026-09-09","wikipedia":"https://en.wikipedia.org/wiki/Exatecan","links":[{"label":"Wikipedia","url":"https://en.wikipedia.org/wiki/Exatecan"}],"tags":[],"related":["topoisomerase-inhibitors","adc-sequencing"],"cancers":[],"sections":[],"technologies":["adc"],"targets":[],"drugs":["izalontamab-brengitecan","tilatamig-samrotecan","ak146d1","puxitatug-samrotecan"],"companies":[],"institutions":[],"pathways":[],"terms":["payload","topoisomerase-i-payloads"],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"category":"ADC chemistry"},"route":"/terms/exatecan/","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":"payload","kind":"term","name":"Payload (ADC)","route":"/terms/payload/"},{"id":"topoisomerase-i-payloads","kind":"term","name":"Topoisomerase-I inhibitor payloads","route":"/terms/topoisomerase-i-payloads/"}],"drug":[{"id":"ak146d1","kind":"drug","name":"AK146D1","route":"/drugs/ak146d1/"},{"id":"izalontamab-brengitecan","kind":"drug","name":"Izalontamab brengitecan","route":"/drugs/izalontamab-brengitecan/"},{"id":"puxitatug-samrotecan","kind":"drug","name":"Puxitatug samrotecan","route":"/drugs/puxitatug-samrotecan/"},{"id":"tilatamig-samrotecan","kind":"drug","name":"Tilatamig samrotecan","route":"/drugs/tilatamig-samrotecan/"}],"pathway":[{"id":"dna-replication-licensing","kind":"pathway","name":"DNA replication & origin licensing","route":"/pathways/dna-replication-licensing/"},{"id":"drug-efflux-pumps","kind":"pathway","name":"Drug efflux pumps (ABC transporters)","route":"/pathways/drug-efflux-pumps/"}]}}