Structure-Based Virtual Screening and De Novo Design of PIM1 Inhibitors with Anticancer Activity from Natural Products

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dc.contributor.authorPark, Hwangseoko
dc.contributor.authorJeon, Jinwonko
dc.contributor.authorKim, Kewonko
dc.contributor.authorChoi, Soyeonko
dc.contributor.authorHong, Sungwooko
dc.date.accessioned2021-04-05T04:30:36Z-
dc.date.available2021-04-05T04:30:36Z-
dc.date.created2021-04-05-
dc.date.created2021-04-05-
dc.date.issued2021-03-
dc.identifier.citationPHARMACEUTICALS, v.14, no.3-
dc.identifier.issn1424-8247-
dc.identifier.urihttp://hdl.handle.net/10203/282291-
dc.description.abstractBackground: the proviral insertion site of Moloney murine leukemia (PIM) 1 kinase has served as a therapeutic target for various human cancers due to the enhancement of cell proliferation and the inhibition of apoptosis. Methods: to identify effective PIM1 kinase inhibitors, structure-based virtual screening of natural products of plant origin and de novo design were carried out using the protein-ligand binding free energy function improved by introducing an adequate dehydration energy term. Results: as a consequence of subsequent enzyme inhibition assays, four classes of PIM1 kinase inhibitors were discovered, with the biochemical potency ranging from low-micromolar to sub-micromolar levels. The results of extensive docking simulations showed that the inhibitory activity stemmed from the formation of multiple hydrogen bonds in combination with hydrophobic interactions in the ATP-binding site. Optimization of the biochemical potency by chemical modifications of the 2-benzylidenebenzofuran-3(2H)-one scaffold led to the discovery of several nanomolar inhibitors with antiproliferative activities against human breast cancer cell lines. Conclusions: these new PIM1 kinase inhibitors are anticipated to serve as a new starting point for the development of anticancer medicine.-
dc.languageEnglish-
dc.publisherMDPI-
dc.titleStructure-Based Virtual Screening and De Novo Design of PIM1 Inhibitors with Anticancer Activity from Natural Products-
dc.typeArticle-
dc.identifier.wosid000634076300001-
dc.identifier.scopusid2-s2.0-85103132684-
dc.type.rimsART-
dc.citation.volume14-
dc.citation.issue3-
dc.citation.publicationnamePHARMACEUTICALS-
dc.identifier.doi10.3390/ph14030275-
dc.contributor.localauthorHong, Sungwoo-
dc.contributor.nonIdAuthorPark, Hwangseo-
dc.contributor.nonIdAuthorChoi, Soyeon-
dc.description.isOpenAccessN-
dc.type.journalArticleArticle-
dc.subject.keywordAuthorvirtual screening-
dc.subject.keywordAuthorde novo design-
dc.subject.keywordAuthorPIM1-
dc.subject.keywordAuthornatural products-
dc.subject.keywordAuthoranticancer activity-
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