Figure 3.

(A) Evolution from compound 1 to compound 3, a Nek2 selective irreversible inhibitor. (B) (1) Design strategy of a selective Nek2 covalent inhibitor and (2) compound 3 computationally modeled in the Nek2 kinase. The alkyne moiety is in proximity to Cys22 for covalent modification of Nek2. The imidazole moiety provides Nek2 selectivity. Computational binding experiments were completed using AutoDock Vina,⁵⁸ and the Nek2 crystal structure was obtained from Innocenti et al.⁵⁵