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Publication Abstract from PubMed

Herein we reveal a simple method for the identification of novel Aurora kinase A inhibitors through substructure searching of an in-house compound library to select compounds for testing. A hydrazone fragment conferring Aurora kinase activity and heterocyclic rings most frequently reported in kinase inhibitors were used as substructure queries to filter the in-house compound library collection prior to testing. Five new series of Aurora kinase inhibitors were identified through this strategy, with IC(50) values ranging from approximately 300 nM to approximately 15 microM, by testing only 133 compounds from a database of approximately 125,000 compounds. Structure-activity relationship studies and X-ray co-crystallographic analysis of the most potent compound, a furanopyrimidine derivative with an IC(50) value of 309 nM toward Aurora kinase A, were carried out. The knowledge gained through these studies could help in the future design of potent Aurora kinase inhibitors.

Identification, SAR studies, and X-ray co-crystallographic analysis of a novel furanopyrimidine aurora kinase A inhibitor.,Coumar MS, Tsai MT, Chu CY, Uang BJ, Lin WH, Chang CY, Chang TY, Leou JS, Teng CH, Wu JS, Fang MY, Chen CH, Hsu JT, Wu SY, Chao YS, Hsieh HP ChemMedChem. 2010 Feb 1;5(2):255-67. PMID:20039358^[1]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.