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2-Aminothiazole Derivatives as Selective Allosteric Modulators of the Protein Kinase CK2. 2. Structure-Based Optimization and Investigation of Effects Specific to the Allosteric Mode of Action.

Bestgen, Benoît; Kufareva, Irina; Seetoh, Weiguang; Abell, Chris; Hartmann, Rolf W; Abagyan, Ruben; Le Borgne, Marc; Filhol, Odile; Cochet, Claude; Lomberget, Thierry; et al. (American Chemical Society, 2019-02-28)

Protein CK2 has gained much interest as an anticancer drug target in the past decade. We had previously described the identification of a new allosteric site on the catalytic α-subunit, along with first small molecule ligands based on the 4-(4-phenylthiazol-2-ylamino)benzoic acid scaffold. In the present work, structure optimizations guided by a binding model led to the identification of the lead compound 2-hydroxy-4-((4-(naphthalen-2-yl)thiazol-2-yl)amino)benzoic acid (27), showing a submicromolar potency against purified CK2α (IC