title: Design of potent and selective hybrid inhibitors of the mitotic kinase Nek2: structure-activity relationship, structural biology, and cellular activity.
abstract: We report herein a series of Nek2 inhibitors based on an aminopyridine scaffold. These compounds have been designed by combining key elements of two previously discovered chemical series. Structure based design led to aminopyridine (R)-21, a potent and selective inhibitor able to modulate Nek2 activity in cells.
authors.affiliation: Cancer Research UK Cancer Therapeutics Unit, Division of Cancer Therapeutics, The Institute of Cancer Research, 15 Cotswold Road, Sutton, Surrey SM2 5NG, United Kingdom.
authors.forename: Paolo
authors.initials: P
authors.lastname: Innocenti
authors.forename: Kwai-Ming J
authors.initials: KM
authors.lastname: Cheung
authors.forename: Savade
authors.initials: S
authors.lastname: Solanki
authors.forename: Corine
authors.initials: C
authors.lastname: Mas-Droux
authors.forename: Fiona
authors.initials: F
authors.lastname: Rowan
authors.forename: Sharon
authors.initials: S
authors.lastname: Yeoh
authors.forename: Kathy
authors.initials: K
authors.lastname: Boxall
authors.forename: Maura
authors.initials: M
authors.lastname: Westlake
authors.forename: Lisa
authors.initials: L
authors.lastname: Pickard
authors.forename: Tara
authors.initials: T
authors.lastname: Hardy
authors.forename: Joanne E
authors.initials: JE
authors.lastname: Baxter
authors.forename: G Wynne
authors.initials: GW
authors.lastname: Aherne
authors.forename: Richard
authors.initials: R
authors.lastname: Bayliss
authors.forename: Andrew M
authors.initials: AM
authors.lastname: Fry
authors.forename: Swen
authors.initials: S
authors.lastname: Hoelder
mesh_terms: D000475:Alkenes / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology; D000631:Aminopyridines / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D000970:Antineoplastic Agents / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D001549:Benzamides / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D001555:Benzene Derivatives / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology; D018360:Crystallography, X-Ray; D015195:Drug Design; D006801:Humans; D008938:Mitosis; D015394:Molecular Structure; D000072379:NIMA-Related Kinases; D010766:Phosphorylation; D017346:Protein Serine-Threonine Kinases / Q000037:antagonists & inhibitors* / Q000378:metabolism; D013237:Stereoisomerism; D013329:Structure-Activity Relationship; D013876:Thiophenes / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology
chemical_list: C574642:4-(2-amino-5-(4-((dimethylamino)methyl)thiophen-2-yl)pyridin-3-yl)-2-((5,5,5-trifluoropent-3-en-2-yl)oxy)benzamide; D000475:Alkenes; D000631:Aminopyridines; D000970:Antineoplastic Agents; D001549:Benzamides; D001555:Benzene Derivatives; D013876:Thiophenes; C089441:NEK2 protein, human; D000072379:NIMA-Related Kinases; D017346:Protein Serine-Threonine Kinases