1276687-26-3Relevant articles and documents
Benzimidazole inhibitors induce a DFG-out conformation of never in mitosis gene a-related kinase 2 (Nek2) without binding to the back pocket and reveal a nonlinear structure-activity relationship
Solanki, Savade,Innocenti, Paolo,Mas-Droux, Corine,Boxall, Kathy,Barillari, Caterina,Van Montfort, Rob L. M.,Aherne, G. Wynne,Bayliss, Richard,Hoelder, Swen
supporting information; experimental part, p. 1626 - 1639 (2011/06/17)
We describe herein the structure-activity relationship (SAR) and cocrystal structures of a series of Nek2 inhibitors derived from the published polo-like kinase 1 (Plk1) inhibitor (R)-1. Our studies reveal a nonlinear SAR for Nek2 and our cocrystal structures show that compounds in this series bind to a DFG-out conformation of Nek2 without extending into the enlarged back pocket commonly found in this conformation. These observations were further investigated, and structure-based design led to Nek2 inhibitors derived from (R)-1 with more than a hundred-fold selectivity against Plk1.
