Fragment-Based Drug Discovery of Potent Protein Kinase C Iota Inhibitors.

Autor: Kwiatkowski J; Experimental Therapeutics Centre , Agency for Science, Technology and Research (A*STAR) , 11 Biopolis Way, Helios #03-10/11 , Singapore 138667 , Singapore., Liu B; Experimental Therapeutics Centre , Agency for Science, Technology and Research (A*STAR) , 11 Biopolis Way, Helios #03-10/11 , Singapore 138667 , Singapore., Tee DHY; Experimental Therapeutics Centre , Agency for Science, Technology and Research (A*STAR) , 11 Biopolis Way, Helios #03-10/11 , Singapore 138667 , Singapore., Chen G; Experimental Therapeutics Centre , Agency for Science, Technology and Research (A*STAR) , 11 Biopolis Way, Helios #03-10/11 , Singapore 138667 , Singapore., Ahmad NHB; Experimental Therapeutics Centre , Agency for Science, Technology and Research (A*STAR) , 11 Biopolis Way, Helios #03-10/11 , Singapore 138667 , Singapore., Wong YX; Experimental Therapeutics Centre , Agency for Science, Technology and Research (A*STAR) , 11 Biopolis Way, Helios #03-10/11 , Singapore 138667 , Singapore., Poh ZY; Experimental Therapeutics Centre , Agency for Science, Technology and Research (A*STAR) , 11 Biopolis Way, Helios #03-10/11 , Singapore 138667 , Singapore., Ang SH; Experimental Therapeutics Centre , Agency for Science, Technology and Research (A*STAR) , 11 Biopolis Way, Helios #03-10/11 , Singapore 138667 , Singapore., Tan ESW; Experimental Therapeutics Centre , Agency for Science, Technology and Research (A*STAR) , 11 Biopolis Way, Helios #03-10/11 , Singapore 138667 , Singapore., Ong EH; Experimental Therapeutics Centre , Agency for Science, Technology and Research (A*STAR) , 11 Biopolis Way, Helios #03-10/11 , Singapore 138667 , Singapore., Nurul Dinie; Experimental Therapeutics Centre , Agency for Science, Technology and Research (A*STAR) , 11 Biopolis Way, Helios #03-10/11 , Singapore 138667 , Singapore., Poulsen A; Experimental Therapeutics Centre , Agency for Science, Technology and Research (A*STAR) , 11 Biopolis Way, Helios #03-10/11 , Singapore 138667 , Singapore., Pendharkar V; Experimental Therapeutics Centre , Agency for Science, Technology and Research (A*STAR) , 11 Biopolis Way, Helios #03-10/11 , Singapore 138667 , Singapore., Sangthongpitag K; Experimental Therapeutics Centre , Agency for Science, Technology and Research (A*STAR) , 11 Biopolis Way, Helios #03-10/11 , Singapore 138667 , Singapore., Lee MA; Experimental Therapeutics Centre , Agency for Science, Technology and Research (A*STAR) , 11 Biopolis Way, Helios #03-10/11 , Singapore 138667 , Singapore., Sepramaniam S; Experimental Therapeutics Centre , Agency for Science, Technology and Research (A*STAR) , 11 Biopolis Way, Helios #03-10/11 , Singapore 138667 , Singapore., Ho SY; Experimental Therapeutics Centre , Agency for Science, Technology and Research (A*STAR) , 11 Biopolis Way, Helios #03-10/11 , Singapore 138667 , Singapore., Cherian J; Experimental Therapeutics Centre , Agency for Science, Technology and Research (A*STAR) , 11 Biopolis Way, Helios #03-10/11 , Singapore 138667 , Singapore., Hill J; Experimental Therapeutics Centre , Agency for Science, Technology and Research (A*STAR) , 11 Biopolis Way, Helios #03-10/11 , Singapore 138667 , Singapore., Keller TH; Experimental Therapeutics Centre , Agency for Science, Technology and Research (A*STAR) , 11 Biopolis Way, Helios #03-10/11 , Singapore 138667 , Singapore., Hung AW; Experimental Therapeutics Centre , Agency for Science, Technology and Research (A*STAR) , 11 Biopolis Way, Helios #03-10/11 , Singapore 138667 , Singapore.
Jazyk: angličtina
Zdroj: Journal of medicinal chemistry [J Med Chem] 2018 May 24; Vol. 61 (10), pp. 4386-4396. Date of Electronic Publication: 2018 May 04.
DOI: 10.1021/acs.jmedchem.8b00060
Abstrakt: Protein kinase C iota (PKC-ι) is an atypical kinase implicated in the promotion of different cancer types. A biochemical screen of a fragment library has identified several hits from which an azaindole-based scaffold was chosen for optimization. Driven by a structure-activity relationship and supported by molecular modeling, a weakly bound fragment was systematically grown into a potent and selective inhibitor against PKC-ι.
Databáze: MEDLINE
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