Topoisomerase I (TOP1)
The enzyme that nicks one DNA strand to relieve twisting while DNA is copied. Camptothecins and the payloads of several antibody-drug conjugates trap it on the DNA so the nick becomes a permanent break when the cell replicates.
Overview
Topoisomerase I relaxes supercoiled DNA by cutting one strand, letting it rotate and resealing it. Camptothecin derivatives such as irinotecan, topotecan, SN-38, DXd and exatecan bind the enzyme-DNA complex and stop the reseal step, so replication forks collide with the trapped complex and create double-strand breaks. The same chemistry is the payload of sacituzumab govitecan, trastuzumab deruxtecan and datopotamab deruxtecan, which explains their shared toxicities of neutropenia and diarrhoea and the cross-resistance seen when one topoisomerase I antibody-drug conjugate follows another.
- Target · the protein and the cell it sits on
- Drug · antibody, small molecule, cell or radioligand
- Effect · signal, damage or kill
In plain words · The enzyme that nicks one DNA strand to relieve twisting while DNA is copied. Camptothecins and the payloads of several antibody-drug conjugates trap it on the DNA so the nick becomes a permanent break when the cell replicates.
- 1 · What it is
The enzyme that nicks one DNA strand to relieve twisting while DNA is copied. Camptothecins and the payloads of several antibody-drug conjugates trap it on the DNA so the nick becomes a permanent break when the cell replicates.
- 2 · What goes wrong in cancer
Type IB topoisomerase that relieves torsional stress during replication and transcription; trapped as a covalent cleavage complex by camptothecins.
- 3 · How drugs use it
No product in this corpus aims at Topoisomerase I (TOP1) yet. Inhibitors are shaped to fit the enzyme's active site so the reaction the cancer relies on stops.
External identifiers
Biology
Type IB topoisomerase that relieves torsional stress during replication and transcription; trapped as a covalent cleavage complex by camptothecins.
- Expressed in all dividing cells; relevant wherever camptothecin or topoisomerase I payload drugs are used
Latest papers
topQuery for this target: (TITLE:"Topoisomerase I" OR ABSTRACT:"Topoisomerase I" OR TITLE:"TOP1" OR ABSTRACT:"TOP1") AND (cancer OR tumor OR tumour OR oncology OR carcinoma OR lymphoma OR leukemia OR leukaemia OR myeloma OR sarcoma OR melanoma OR glioma). Results are unfiltered search hits about Topoisomerase I (TOP1), not a curated reading list.
Similar pages
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