DC Field | Value | Language |
---|---|---|
dc.contributor.author | Park, Hwangseo | ko |
dc.contributor.author | Jeon, Jinwon | ko |
dc.contributor.author | Kim, Kewon | ko |
dc.contributor.author | Choi, Soyeon | ko |
dc.contributor.author | Hong, Sungwoo | ko |
dc.date.accessioned | 2021-04-05T04:30:36Z | - |
dc.date.available | 2021-04-05T04:30:36Z | - |
dc.date.created | 2021-04-05 | - |
dc.date.created | 2021-04-05 | - |
dc.date.created | 2021-04-05 | - |
dc.date.issued | 2021-03 | - |
dc.identifier.citation | PHARMACEUTICALS, v.14, no.3 | - |
dc.identifier.issn | 1424-8247 | - |
dc.identifier.uri | http://hdl.handle.net/10203/282291 | - |
dc.description.abstract | Background: 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.language | English | - |
dc.publisher | MDPI | - |
dc.title | Structure-Based Virtual Screening and De Novo Design of PIM1 Inhibitors with Anticancer Activity from Natural Products | - |
dc.type | Article | - |
dc.identifier.wosid | 000634076300001 | - |
dc.identifier.scopusid | 2-s2.0-85103132684 | - |
dc.type.rims | ART | - |
dc.citation.volume | 14 | - |
dc.citation.issue | 3 | - |
dc.citation.publicationname | PHARMACEUTICALS | - |
dc.identifier.doi | 10.3390/ph14030275 | - |
dc.contributor.localauthor | Hong, Sungwoo | - |
dc.contributor.nonIdAuthor | Park, Hwangseo | - |
dc.contributor.nonIdAuthor | Choi, Soyeon | - |
dc.description.isOpenAccess | Y | - |
dc.type.journalArticle | Article | - |
dc.subject.keywordAuthor | virtual screening | - |
dc.subject.keywordAuthor | de novo design | - |
dc.subject.keywordAuthor | PIM1 | - |
dc.subject.keywordAuthor | natural products | - |
dc.subject.keywordAuthor | anticancer activity | - |
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