5W84

CRYSTAL STRUCTURE OF IRAK-4 WITH A 4,6-DIAMINONICOTINAMIDE INHIBITOR (COMPOUND NUMBER 4)

Summary for 5W84

• Entry DOI: 10.2210/pdb5w84/pdb
• Related: 5w85 5w86
• Descriptor: Interleukin-1 receptor-associated kinase 4, 4-(benzylamino)-6-[(2-oxo-2,3-dihydro-1H-indol-5-yl)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: Cytoplasm : Q9NWZ3
• Total number of polymer chains: 2
• Total formula weight: 69291.95

Authors

Sack, J.S. (deposition date: 2017-06-21, release date: 2017-10-11, Last modification date: 2024-11-13)

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

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: 28947151
DOI: 10.1016/j.bmcl.2017.09.029

Experimental method

X-RAY DIFFRACTION (2.9 Å)