{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,23]],"date-time":"2026-10-23T21:04:11Z","timestamp":1792789451580,"version":"4.5.0"},"reference-count":96,"publisher":"MDPI AG","issue":"6","license":[{"start":{"date-parts":[[2023,3,17]],"date-time":"2023-03-17T00:00:00Z","timestamp":1679011200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100006769","name":"Russian Science Foundation","doi-asserted-by":"publisher","award":["21-14-00105"],"award-info":[{"award-number":["21-14-00105"]}],"id":[{"id":"10.13039\/501100006769","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100006769","name":"Russian Science Foundation","doi-asserted-by":"publisher","award":["121031300041-4"],"award-info":[{"award-number":["121031300041-4"]}],"id":[{"id":"10.13039\/501100006769","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Russian state-funded project for ICBFM SB RAS","award":["21-14-00105"],"award-info":[{"award-number":["21-14-00105"]}]},{"name":"Russian state-funded project for ICBFM SB RAS","award":["121031300041-4"],"award-info":[{"award-number":["121031300041-4"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Tyrosyl-DNA phosphodiesterase 1 (TDP1) is an important repair enzyme that removes various covalent adducts from the 3\u2032 end of DNA. Particularly, covalent complexes of topoisomerase 1 (TOP1) with DNA stabilized by DNA damage or by various chemical agents are an examples of such adducts. Anticancer drugs such as the TOP1 poisons topotecan and irinotecan are responsible for the stabilization of these complexes. TDP1 neutralizes the effect of these anticancer drugs, eliminating the DNA adducts. Therefore, the inhibition of TDP1 can sensitize tumor cells to the action of TOP1 poisons. This review contains information about methods for determining the TDP1 activity, as well as describing the inhibitors of these enzyme derivatives of natural biologically active substances, such as aminoglycosides, nucleosides, polyphenolic compounds, and terpenoids. Data on the efficiency of combined inhibition of TOP1 and TDP1 in vitro and in vivo are presented.<\/jats:p>","DOI":"10.3390\/ijms24065781","type":"journal-article","created":{"date-parts":[[2023,3,20]],"date-time":"2023-03-20T04:33:31Z","timestamp":1679286811000},"page":"5781","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":34,"title":["Natural Products and Their Derivatives as Inhibitors of the DNA Repair Enzyme Tyrosyl-DNA Phosphodiesterase 1"],"prefix":"10.3390","volume":"24","author":[{"given":"Alexandra L.","family":"Zakharenko","sequence":"first","affiliation":[{"name":"Novosibirsk Institute of Chemical Biology and Fundamental Medicine, Siberian Branch of the Russian Academy of Sciences, 8, Akademika Lavrentieva Ave., Novosibirsk 630090, Russia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8627-3453","authenticated-orcid":false,"given":"Olga A.","family":"Luzina","sequence":"additional","affiliation":[{"name":"N. N. Vorozhtsov Novosibirsk Institute of Organic Chemistry, Siberian Branch of the Russian Academy of Sciences, 9, Akademika Lavrentieva Ave., Novosibirsk 630090, Russia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Arina A.","family":"Chepanova","sequence":"additional","affiliation":[{"name":"Novosibirsk Institute of Chemical Biology and Fundamental Medicine, Siberian Branch of the Russian Academy of Sciences, 8, Akademika Lavrentieva Ave., Novosibirsk 630090, Russia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8360-1041","authenticated-orcid":false,"given":"Nadezhda S.","family":"Dyrkheeva","sequence":"additional","affiliation":[{"name":"Novosibirsk Institute of Chemical Biology and Fundamental Medicine, Siberian Branch of the Russian Academy of Sciences, 8, Akademika Lavrentieva Ave., Novosibirsk 630090, Russia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nariman F.","family":"Salakhutdinov","sequence":"additional","affiliation":[{"name":"N. N. Vorozhtsov Novosibirsk Institute of Organic Chemistry, Siberian Branch of the Russian Academy of Sciences, 9, Akademika Lavrentieva Ave., Novosibirsk 630090, Russia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5980-8889","authenticated-orcid":false,"given":"Olga I.","family":"Lavrik","sequence":"additional","affiliation":[{"name":"Novosibirsk Institute of Chemical Biology and Fundamental Medicine, Siberian Branch of the Russian Academy of Sciences, 8, Akademika Lavrentieva Ave., Novosibirsk 630090, Russia"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2023,3,17]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"267","DOI":"10.1038\/ng987","article-title":"Mutation of TDP1, Encoding a Topoisomerase I-Dependent DNA Damage Repair Enzyme, in Spinocerebellar Ataxia with Axonal Neuropathy","volume":"32","author":"Takashima","year":"2002","journal-title":"Nat. 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