Summary for 9PSS
| Entry DOI | 10.2210/pdb9pss/pdb |
| Descriptor | Interleukin-1 receptor-associated kinase 4, (7P,8S)-7-{(5M)-5-[1-(oxan-4-yl)-1H-1,2,3-triazol-4-yl]-4-[(propan-2-yl)amino]pyridin-2-yl}pyrrolo[1,2-b]pyridazine-3-carbonitrile, SULFATE ION, ... (4 entities in total) |
| Functional Keywords | kinase, phosphorylated, signaling protein, inhibitor complex, immune system, transferase, transferase-transferase inhibitor complex, transferase/transferase inhibitor |
| Biological source | Homo sapiens (human) |
| Total number of polymer chains | 2 |
| Total formula weight | 69576.20 |
| Authors | |
| Primary citation | Ammann, S.E.,Brizgys, G.,Ferrao, R.D.,Wright, N.E.,Mukherjee, P.K.,Bacon, E.M.,Chin, E.,Chou, C.,Cottell, J.J.,Hammond, A.,Ndukwe, M.S.,Park, G.Y.,Shatskikh, M.E.,Suekawa-Pirrone, K.,Warr, M.R.,Yang, Z.Y.,Zipfel, S.M.,Taylor, J.G. Examination of Noncanonical Kinase Hinge Binders Leads to Thiadiazoles as Potent IRAK4 Inhibitors. Acs Med.Chem.Lett., 17:175-182, 2026 Cited by PubMed Abstract: A hallmark of most known small-molecule orthosteric kinase inhibitors is hydrogen-bonding to the hinge-region of the kinase to mimic the hinge interaction of adenine. Herein we report our studies on deviation from canonical hinge-binders in the context of IRAK4 inhibitors. Small-molecule inhibitors of IRAK4 have generated interest as potential treatments for inflammatory diseases. Notably, in our discovery efforts we identified pyridinyl-thiadiazoles as noncanonical hinge-binders. X-ray structural evidence supports that the thiadiazole moiety engages in a rare intermolecular noncovalent sulfur-oxygen interaction. This thiadiazole series, exemplified by compounds and , has shown promise for potent, selective, orally bioavailable IRAK4 inhibitors. PubMed: 41531974DOI: 10.1021/acsmedchemlett.5c00602 PDB entries with the same primary citation |
| Experimental method | X-RAY DIFFRACTION (1.93 Å) |
Structure validation
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