Structure-Based virtual screening and de novo design of PIM1 inhibitors with anticancer activity from natural products

Hwangseo Park, Jinwon Jeon, Kewon Kim, Soyeon Choi, Sungwoo Hong

Research output: Contribution to journalArticlepeer-review

7 Scopus citations


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, structurebased 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.

Original languageEnglish
Article number275
Issue number3
StatePublished - Mar 2021


  • Anticancer activity
  • De novo design
  • Natural products
  • PIM1
  • Virtual screening


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