5W85

CRYSTAL STRUCTURE OF IRAK-4 WITH A 4,6-DIAMINONICOTINAMIDE INHIBITOR (COMPOUND NUMBER 9)

Summary for 5W85

• Entry DOI: 10.2210/pdb5w85/pdb
• Related: 5w84 5w86
• Descriptor: Interleukin-1 receptor-associated kinase 4, 6-[(1,3-benzothiazol-6-yl)amino]-4-{[(2S)-1-hydroxy-3-phenylpropan-2-yl]amino}-N-methylpyridine-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: 69412.18

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 (2.25 Å)