1414951-60-2Relevant academic research and scientific papers
Fragment-based Discovery of a Small-Molecule Protein Kinase C-iota Inhibitor Binding Post-kinase Domain Residues
Kwiatkowski, Jacek,Baburajendran, Nithya,Poulsen, Anders,Liu, Boping,Tee, Doris Hui Ying,Wong, Yun Xuan,Poh, Zhi Ying,Ong, Esther H.Q.,Dinie, Nurul,Cherian, Joseph,Jansson, Anna Elisabet,Hill, Jeffrey,Keller, Thomas H.,Hung, Alvin W.
, p. 318 - 323 (2019/03/19)
The atypical protein kinase C-iota (PKC-l) enzyme is implicated in various cancers and has been put forward as an attractive target for developing anticancer therapy. A high concentration biochemical screen identified pyridine fragment weakly inhibiting PKC-l with IC50 = 424 μM. Driven by structure-activity relationships and guided by docking hypothesis, the weakly bound fragment was eventually optimized into a potent inhibitor of PKC-l (IC50= 270 nM). Through the course of the optimization, an intermediate compound was crystallized with the protein, and careful analysis of the X-ray crystal structure revealed a unique binding mode involving the post-kinase domain (C-terminal tail) of PKC-l.
PYRIDINE-AND PYRAZINE DERIVATIVES
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Page/Page column 94; 99, (2012/12/13)
Compounds of the formula (I) in which R, R1 and X have the meanings indicated in Claim 1, are inhibitors of TBK1 and IKKε and can be employed, inter alia, for the treatment of cancer and inflammatory diseases
