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Updated: Mar 20, 2026

Kinase Inhibitor Screening In Self-assembled Human Protein Microarrays
Published on: October 23, 2019
Identification and Validation of an Inhibitor of the Protein Kinases PIM and DYRK
Gyula Bencze1, Prabhadevi Venkataramani1, Elad Elkayam1,2
1Cold Spring Harbor Laboratory, Cold Spring Harbor, New York, New York 11724, United States.
Abstract:
Fermented wheat germ extract (FWGE), a nutraceutical with reported anticancer properties, contains numerous biologically active molecules, but its therapeutic constituents remain unclear. In this study, we identify and characterize a novel small-molecule protein kinase inhibitor isolated from FWGE, designated F10V6W0. Through preparative high-performance liquid chromatography and structural elucidation via X-ray crystallography, this compound was revealed to be a unique benzothiazole. Kinase profiling demonstrated its 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. We determined the cocrystal structure of CSH-4044 bound to PIM1, revealing ATP-competitive binding and critical hydrophobic and hydrogen-bonding interactions. Functionally, CSH-4044 suppressed PIM3-driven BAD phosphorylation in pancreatic cancer cells and reduced DYRK1A-mediated Tau phosphorylation in neuronal cells. Our findings position CSH-4044 as a promising lead for targeting PIM and DYRK kinase families and highlight FWGE as a potential therapeutic compounds.
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