title: Structure-based design of imidazo[1,2-a]pyrazine derivatives as selective inhibitors of Aurora-A kinase in cells.
abstract: Co-crystallisation of the imidazo[1,2-a]pyrazine derivative 15 (3-chloro-N-(4-morpholinophenyl)-6-(pyridin-3-yl)imidazo[1,2-a]pyrazin-8-amine) with Aurora-A provided an insight into the interactions of this class of compound with Aurora kinases. This led to the design and synthesis of potent Aurora-A inhibitors demonstrating up to 70-fold selectivity in cell-based Aurora kinase pharmacodynamic biomarker assays.
authors.affiliation: Cancer Research UK Cancer Therapeutics Unit, The Institute of Cancer Research, Sutton, Surrey, United Kingdom.
authors.forename: Nathalie
authors.initials: N
authors.lastname: Bouloc
authors.forename: Jonathan M
authors.initials: JM
authors.lastname: Large
authors.forename: Magda
authors.initials: M
authors.lastname: Kosmopoulou
authors.forename: Chongbo
authors.initials: C
authors.lastname: Sun
authors.forename: Amir
authors.initials: A
authors.lastname: Faisal
authors.forename: Mizio
authors.initials: M
authors.lastname: Matteucci
authors.forename: Jóhannes
authors.initials: J
authors.lastname: Reynisson
authors.forename: Nathan
authors.initials: N
authors.lastname: Brown
authors.forename: Butrus
authors.initials: B
authors.lastname: Atrash
authors.forename: Julian
authors.initials: J
authors.lastname: Blagg
authors.forename: Edward
authors.initials: E
authors.lastname: McDonald
authors.forename: Spiros
authors.initials: S
authors.lastname: Linardopoulos
authors.forename: Richard
authors.initials: R
authors.lastname: Bayliss
authors.forename: Vassilios
authors.initials: V
authors.lastname: Bavetsias
mesh_terms: D000970:Antineoplastic Agents / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology*; D064127:Aurora Kinases; D045744:Cell Line, Tumor; D018360:Crystallography, X-Ray; D006801:Humans; D008958:Models, Molecular; D009369:Neoplasms / Q000188:drug therapy; D047428:Protein Kinase Inhibitors / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology*; D017346:Protein Serine-Threonine Kinases / Q000037:antagonists & inhibitors* / Q000737:chemistry / Q000378:metabolism; D011719:Pyrazines / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology*; D013329:Structure-Activity Relationship
chemical_list: D000970:Antineoplastic Agents; D047428:Protein Kinase Inhibitors; D011719:Pyrazines; D064127:Aurora Kinases; D017346:Protein Serine-Threonine Kinases