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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.

SUBMITTER: Innocenti P

PROVIDER: S-EPMC3935458 | biostudies-literature | 2012 Apr

REPOSITORIES: biostudies-literature

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Design of potent and selective hybrid inhibitors of the mitotic kinase Nek2: structure-activity relationship, structural biology, and cellular activity.

Innocenti Paolo P Cheung Kwai-Ming J KM Solanki Savade S Mas-Droux Corine C Rowan Fiona F Yeoh Sharon S Boxall Kathy K Westlake Maura M Pickard Lisa L Hardy Tara T Baxter Joanne E JE Aherne G Wynne GW Bayliss Richard R Fry Andrew M AM Hoelder Swen S

Journal of medicinal chemistry 20120323 7

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. ...[more]

PMID: 22404346

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