Identification and Validation of an Inhibitor of the Protein Kinases PIM and DYRK - PubMed
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- #anticancer nutraceutical
- #PIM and DYRK kinases
- #protein kinase inhibitor
- Fermented wheat germ extract (FWGE) has anticancer properties but its therapeutic constituents are unclear.
- A novel small-molecule protein kinase inhibitor, F10V6W0, was isolated from FWGE and identified as a unique benzothiazole.
- F10V6W0 shows selectivity toward PIM and DYRK protein kinase families.
- A chemically synthesized version, CSH-4044, mirrored the activity of the natural product, confirming structural integrity and biological equivalence.
- The cocrystal structure of CSH-4044 bound to PIM1 revealed ATP-competitive binding and critical hydrophobic and hydrogen-bonding interactions.
- CSH-4044 suppressed PIM3-driven BAD phosphorylation in pancreatic cancer cells and reduced DYRK1A-mediated Tau phosphorylation in neuronal cells.
- CSH-4044 is a promising lead for targeting PIM and DYRK kinase families and highlights FWGE as a potential source of therapeutic compounds.