Exploring the pivotal role of the CK2 hinge region sub-pocket in binding with tricyclic quinolone analogues by computational analysis was written by Zhou, Yue;Zhang, Na;Tang, Shan;Qi, Xiaoqian;Zhao, Lijiao;Zhong, Rugang;Peng, Yongzhen. And the article was included in Molecules in 2017.Product Details of 1009820-21-6 This article mentions the following:
Protein kinase CK2 has been considered as an attractive therapeutic target of cancer therapy. The tricyclic quinoline compound CX-4945 is the first representative of CK2 inhibitors used in human clin. trials. The binding of non-2,6-naphtyridine substituted compounds 27e (IC50 > 500 nM) and 27h (IC50 > 1000 nM) to CK2 is abolished. However, the unbinding mechanisms due to the key pharmacophore group replacement of compounds 27e and 27h are unveiled. In the present work, combined computational anal. was performed to investigate the underlying structural basis of the low-affinity of two systems. As indicated in the results, the loss of hydrogen bonds between the non-2,6-naphtyridine and the hinge region destroyed the proper recognition of the two complexes. Besides, the allosteric mechanisms between the deviated ligands and the changed regions (G-loop, C-loop and β4/β5 loop) are proposed. Furthermore, energetic anal. was evaluated by detailed energy calculation and residue-based energy decomposition More importantly, the summary of known polar pharmacophore groups elucidates the pivotal roles of hinge region sub-pocket in the binding of CK2 inhibitors. These results provide rational clues to the fragment-based design of more potent CK2 inhibitors. In the experiment, the researchers used many compounds, for example, 5-((3-Chlorophenyl)amino)benzo[c][2,6]naphthyridine-8-carboxylic acid (cas: 1009820-21-6Product Details of 1009820-21-6).
5-((3-Chlorophenyl)amino)benzo[c][2,6]naphthyridine-8-carboxylic acid (cas: 1009820-21-6) belongs to naphthyridine derivatives. Functionalized naphthyridines and their benzo/heterofused analogs are present in numerous marine products and reported to possess wide-ranging activities such as antiproliferative, antiaggressive, and HIV-1 integrase inhibition in addition to their use as anti-HCV agents. 1,6-Naphthyridine and some of its derivatives have been reported to have medicinal, electronic, and catalytic properties. But none of these investigations has yet resulted in any practical applications. Very few metal complexes of naphthyridines other than 1,8-naphthyridine have been described.Product Details of 1009820-21-6
Referemce:
1,8-Naphthyridine – Wikipedia,
1,8-Naphthyridine | C8H6N2 – PubChem