9YKI
Crystal structure of human PIM1 kinase bound with CSH-4044 inhibitor
This is a non-PDB format compatible entry.
Summary for 9YKI
| Entry DOI | 10.2210/pdb9yki/pdb |
| Descriptor | Serine/threonine-protein kinase pim-1, (2,5-dihydroxy-4-methoxyphenyl)(6-hydroxy-5-methoxy-1,3-benzothiazol-2-yl)methanone, GLYCEROL, ... (5 entities in total) |
| Functional Keywords | kinase, inhibitor, co-crystallization, transferase |
| Biological source | Homo sapiens (human) |
| Total number of polymer chains | 1 |
| Total formula weight | 36276.46 |
| Authors | |
| Primary citation | Bencze, G.,Venkataramani, P.,Elkayam, E.,Rivera, K.D.,Garg, A.,Szabadakai, I.,Orfi, L.,Joshua-Tor, L.,Pappin, D.J.,Tonks, N.K. Identification and Validation of an Inhibitor of the Protein Kinases PIM and DYRK. J.Med.Chem., 2026 Cited by PubMed 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. PubMed: 41849779DOI: 10.1021/acs.jmedchem.5c03226 PDB entries with the same primary citation |
| Experimental method | X-RAY DIFFRACTION (1.95 Å) |
Structure validation
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