5W86
CRYSTAL STRUCTURE OF JAK3 KINASE DOMAIN WITH A 4,6-DIAMINONICOTINAMIDE INHIBITOR (COMPOUND NUMBER 7)
Summary for 5W86
| Entry DOI | 10.2210/pdb5w86/pdb |
| Related | 5w84 5w85 |
| Descriptor | Tyrosine-protein kinase JAK3, 4-(benzylamino)-6-({4-[(1-methylpiperidin-4-yl)carbamoyl]phenyl}amino)pyridine-3-carboxamide (3 entities in total) |
| Functional Keywords | serine/threonine protein kinase, transferase, transferase-transferase inhibitor complex, transferase/transferase inhibitor |
| Biological source | Homo sapiens (Human) |
| Cellular location | Endomembrane system ; Peripheral membrane protein : P52333 |
| Total number of polymer chains | 4 |
| Total formula weight | 133267.94 |
| Authors | Sack, J.S. (deposition date: 2017-06-21, release date: 2017-10-11, Last modification date: 2017-10-25) |
| Primary citation | Bhide, R.S.,Keon, A.,Weigelt, C.,Sack, J.S.,Schmidt, R.J.,Lin, S.,Xiao, H.Y.,Spergel, S.H.,Kempson, J.,Pitts, W.J.,Carman, J.,Poss, M.A. Discovery and structure-based design of 4,6-diaminonicotinamides as potent and selective IRAK4 inhibitors. Bioorg. Med. Chem. Lett., 27:4908-4913, 2017 Cited by PubMed Abstract: The identification of small molecule inhibitors of IRAK4 for the treatment of autoimmune diseases has been an area of intense research. We discovered novel 4,6-diaminonicotinamides which potently inhibit IRAK4. Optimization efforts were aided by X-ray crystal structures of inhibitors bound to IRAK4. Structure activity relationship (SAR) studies led to the identification of compound 29 which exhibited sub-micromolar potency in a LTA stimulated cellular assay. PubMed: 28947151DOI: 10.1016/j.bmcl.2017.09.029 PDB entries with the same primary citation |
| Experimental method | X-RAY DIFFRACTION (2.61 Å) |
Structure validation
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