5T1S

Irak4 kinase - compound 1 co-structure

Summary for 5T1S

• Entry DOI: 10.2210/pdb5t1s/pdb
• Related: 5T1T
• Descriptor: Interleukin-1 receptor-associated kinase 4, 5-[3-(3,5-dimethylphenyl)-4-[4-(methylamino)butyl]quinolin-6-yl]pyridin-3-ol (3 entities in total)
• Functional Keywords: inase, phosphatase, transferase-transferase inhibitor complex, transferase/transferase inhibitor
• Biological source: Homo sapiens (Human)
• Cellular location: Cytoplasm : Q9NWZ3
• Total number of polymer chains: 4
• Total formula weight: 137470.94

Authors

Fischmann, T.O. (deposition date: 2016-08-22, release date: 2017-05-03, Last modification date: 2024-11-20)

Primary citation

Smith, G.F.,Altman, M.D.,Andresen, B.,Baker, J.,Brubaker, J.D.,Chen, H.,Chen, Y.,Childers, M.,Donofrio, A.,Ferguson, H.,Fischer, C.,Fischmann, T.O.,Gibeau, C.,Hicks, A.,Jin, S.,Kattar, S.,Kleinschek, M.A.,Leccese, E.,Lesburg, C.,Li, C.,Lim, J.,Liu, D.,Maclean, J.K.F.,Mansoor, F.,Moy, L.Y.,Mulrooney, E.F.,Necheva, A.S.,Presland, J.,Rakhilina, L.,Yang, R.,Torres, L.,Zhang-Hoover, J.,Northrup, A.
Identification of quinazoline based inhibitors of IRAK4 for the treatment of inflammation.
Bioorg. Med. Chem. Lett., 27:2721-2726, 2017

PubMed Abstract: Interleukin-1 receptor associated kinase 4 (IRAK4) has been implicated in IL-1R and TLR based signaling. Therefore selective inhibition of the kinase activity of this protein represents an attractive target for the treatment of inflammatory diseases. Medicinal chemistry optimization of high throughput screening (HTS) hits with the help of structure based drug design led to the identification of orally-bioavailable quinazoline based IRAK4 inhibitors with excellent pharmacokinetic profile and kinase selectivity. These highly selective IRAK4 compounds show activity in vivo via oral dosing in a TLR7 driven model of inflammation.

PubMed: 28501511
DOI: 10.1016/j.bmcl.2017.04.050

Experimental method

X-RAY DIFFRACTION (2.3 Å)