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dc.contributor.authorMatias-Barrios, Victor M
dc.contributor.authorRadaeva, Mariia
dc.contributor.authorSong, Yi
dc.contributor.authorAlperstein, Zaccary
dc.contributor.authorLee, Ahn R
dc.contributor.authorSchmitt, Veronika
dc.contributor.authorLee, Joseph
dc.contributor.authorBan, Fuqiang
dc.contributor.authorXie, Ning
dc.contributor.authorQi, Jianfei
dc.contributor.authorLallous, Nada
dc.contributor.authorGleave, Martin E
dc.contributor.authorCherkasov, Artem
dc.contributor.authorDong, Xuesen
dc.date.accessioned2021-03-03T18:55:54Z
dc.date.available2021-03-03T18:55:54Z
dc.date.issued2021-02-01
dc.identifier.urihttp://hdl.handle.net/10713/14800
dc.description.sponsorshipPoison inhibitors of DNA topoisomerase II (TOP2) are clinically used drugs that cause cancer cell death by inducing DNA damage, which mechanism of action is also associated with serious side effects such as secondary malignancy and cardiotoxicity. In contrast, TOP2 catalytic inhibitors induce limited DNA damage, have low cytotoxicity, and are effective in suppressing cancer cell proliferation. They have been sought after to be prospective anticancer therapies. Herein the discovery of new TOP2 catalytic inhibitors is described. A new druggable pocket of TOP2 protein at its DNA binding domain was used as a docking site to virtually screen ~6 million molecules from the ZINC15 library. The lead compound, T60, was characterized to be a catalytic TOP2 inhibitor that binds TOP2 protein and disrupts TOP2 from interacting with DNA, resulting in no DNA cleavage. It has low cytotoxicity, but strongly inhibits cancer cell proliferation and xenograft growth. T60 also inhibits androgen receptor activity and prostate cancer cell growth. These results indicate that T60 is a promising candidate compound that can be further developed into new anticancer drugs. © Copyright © 2021 Matias-Barrios, Radaeva, Song, Alperstein, Lee, Schmitt, Lee, Ban, Xie, Qi, Lallous, Gleave, Cherkasov and Dong.en_US
dc.description.urihttps://doi.org/10.3389/fonc.2020.633142en_US
dc.language.isoenen_US
dc.publisherFrontiers Media S.A.en_US
dc.relation.ispartofFrontiers in Oncologyen_US
dc.rightsCopyright © 2021 Matias-Barrios, Radaeva, Song, Alperstein, Lee, Schmitt, Lee, Ban, Xie, Qi, Lallous, Gleave, Cherkasov and Dong.en_US
dc.subjectandrogen receptoren_US
dc.subjectcatalytic inhibitoren_US
dc.subjectcomputer aided drug designen_US
dc.subjectprostate canceren_US
dc.subjecttopoisomerase IIen_US
dc.titleDiscovery of New Catalytic Topoisomerase II Inhibitors for Anticancer Therapeuticsen_US
dc.typeArticleen_US
dc.identifier.doi10.3389/fonc.2020.633142
dc.identifier.pmid33598437
dc.source.volume10
dc.source.beginpage633142
dc.source.endpage
dc.source.countrySwitzerland


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