5MPJ

1-(2-chloro-[1,1'-biphenyl]-4-yl)-N-methylethanamine

5MPJ の概要

• エントリーDOI: 10.2210/pdb5mpj/pdb
• 分子名称: Casein kinase II subunit alpha, ADENOSINE-5'-DIPHOSPHATE, INOSITOL HEXAKISPHOSPHATE, ... (5 entities in total)
• 機能のキーワード: ck2alpha, ck2a, fragment based drug discovery, high concentration screening, selective atp competitive inhibitors, surface entrophy reduction, transferase
• 由来する生物種: Homo sapiens (Human)
• タンパク質・核酸の鎖数: 2
• 化学式量合計: 84269.58

構造登録者

Brear, P.,De Fusco, C.,Georgiou, K.,Iegre, J.,Sore, H.,Hyvonen, M.,Spring, D. (登録日: 2016-12-16, 公開日: 2017-05-24, 最終更新日: 2024-01-17)

主引用文献

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

実験手法

X-RAY DIFFRACTION (2.14 Å)