5CU0

Crystal structure of CK2alpha with 2-hydroxy-5-methylbenzoic acid and N-(3-(3-chloro-4-(phenyl)benzylamino)propyl)acetamide bound

Summary for 5CU0

• Entry DOI: 10.2210/pdb5cu0/pdb
• Descriptor: Casein kinase II subunit alpha, N-(3-{[(2-chlorobiphenyl-4-yl)methyl]amino}propyl)acetamide, 2-hydroxy-5-methylbenzoic acid, ... (5 entities in total)
• Functional Keywords: ck2alpha, ck2a, fragment based drug discovery, high concentration screening, selective atp competitive inhibitors, surface entrophy reduction, transferase
• Biological source: Homo sapiens (Human)
• Cellular location: Nucleus : P68400
• Total number of polymer chains: 2
• Total formula weight: 84566.22

Authors

Brear, P.,De Fusco, C.,Georgiou, K.H.,Spring, D.,Hyvonen, M. (deposition date: 2015-07-24, release date: 2016-11-30, Last modification date: 2024-01-10)

Primary citation

De Fusco, C.,Brear, P.,Iegre, J.,Georgiou, K.H.,Sore, H.F.,Hyvonen, M.,Spring, D.R.
A fragment-based approach leading to the discovery of a novel binding site and the selective CK2 inhibitor CAM4066.
Bioorg. Med. Chem., 25:3471-3482, 2017

PubMed Abstract: Recently we reported the discovery of a potent and selective CK2α inhibitor CAM4066. This compound inhibits CK2 activity by exploiting a pocket located outside the ATP binding site (αD pocket). Here we describe in detail the journey that led to the discovery of CAM4066 using the challenging fragment linking strategy. Specifically, we aimed to develop inhibitors by linking a high-affinity fragment anchored in the αD site to a weakly binding warhead fragment occupying the ATP site. Moreover, we describe the remarkable impact that molecular modelling had on the development of this novel chemical tool. The work described herein shows potential for the development of a novel class of CK2 inhibitors.

PubMed: 28495381
DOI: 10.1016/j.bmc.2017.04.037

Experimental method

X-RAY DIFFRACTION (2.18 Å)