Second-generation CK2α inhibitors targeting the αD pocket.

ABSTRACT: CK2 is a critical cell cycle regulator that also promotes various anti-apoptotic mechanisms. Development of ATP-non-competitive inhibitors of CK2 is a very attractive strategy considering that the ATP binding site is highly conserved among other kinases. We have previously utilised a pocket outside the active site to develop a novel CK2 inhibitor, CAM4066. Whilst CAM4066 bound to this new pocket it was also interacting with the ATP site: herein, we describe an example of a CK2α inhibitor that binds completely outside the active site. This second generation αD-site binding inhibitor, compound CAM4712 (IC₅₀ = 7 μM, GI₅₀ = 10.0 ± 3.6 μM), has numerous advantages over the previously reported CAM4066, including a reduction in the number of rotat

SUBMITTER: Iegre J 

PROVIDER: S-EPMC5916021 | biostudies-literature | 2018 Mar

REPOSITORIES: biostudies-literature