4ZTL

Irak4-inhibitor co-structure

Summary for 4ZTL

• Entry DOI: 10.2210/pdb4ztl/pdb
• Related: 4ZTM 4ZTN
• Descriptor: Interleukin-1 receptor-associated kinase 4, (1R,2S,3R,5R)-3-{[5-(1,3-benzothiazol-2-yl)-2-(propylamino)pyrimidin-4-yl]amino}-5-(hydroxymethyl)cyclopentane-1,2-diol (3 entities in total)
• Functional Keywords: kinase, 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: 137486.82

Authors

Fischmann, T.O. (deposition date: 2015-05-14, release date: 2015-09-02, Last modification date: 2024-11-06)

Primary citation

Seganish, W.M.,Fischmann, T.O.,Sherborne, B.,Matasi, J.,Lavey, B.,McElroy, W.T.,Tulshian, D.,Tata, J.,Sondey, C.,Garlisi, C.G.,Devito, K.,Fossetta, J.,Lundell, D.,Niu, X.
Discovery and Structure Enabled Synthesis of 2,6-Diaminopyrimidin-4-one IRAK4 Inhibitors.
Acs Med.Chem.Lett., 6:942-947, 2015

PubMed Abstract: We report the identification and synthesis of a series of aminopyrimidin-4-one IRAK4 inhibitors. Through high throughput screening, an aminopyrimidine hit was identified and modified via structure enabled design to generate a new, potent, and kinase selective pyrimidin-4-one chemotype. This chemotype is exemplified by compound 16, which has potent IRAK4 inhibition activity (IC50 = 27 nM) and excellent kinase selectivity (>100-fold against 99% of 111 tested kinases), and compound 31, which displays potent IRAK4 activity (IC50 = 93 nM) and good rat bioavailability (F = 42%).

PubMed: 26288698
DOI: 10.1021/acsmedchemlett.5b00279

Experimental method

X-RAY DIFFRACTION (2.39 Å)