Downfalls of chemical probes acting at the kinase ATP-site: CK2 as a case study was written by Atkinson, Eleanor L.;Iegre, Jessica;Brear, Paul D.;Zhabina, Elizabeth A.;Hyvonen, Marko;Spring, David R.. And the article was included in Molecules in 2021.Formula: C19H12ClN3O2 This article mentions the following:
Protein kinases are a large class of enzymes with numerous biol. roles and many have been implicated in a vast array of diseases, including cancer and the novel coronavirus infection COVID-19. Thus, the development of chem. probes to selectively target each kinase is of great interest. Inhibition of protein kinases with ATP-competitive inhibitors has historically been the most widely used method. However, due to the highly conserved structures of ATP-sites, the identification of truly selective chem. probes is challenging. We use the Ser/Thr kinase CK2 as an example to highlight the historical challenges in effective and selective chem. probe development, alongside recent advances in the field and alternative strategies aiming to overcome these problems. The methods utilized for CK2 can be applied to an array of protein kinases to aid in the discovery of chem. probes to further understand each kinase’s biol., with wide-reaching implications for drug development. In the experiment, the researchers used many compounds, for example, 5-((3-Chlorophenyl)amino)benzo[c][2,6]naphthyridine-8-carboxylic acid (cas: 1009820-21-6Formula: C19H12ClN3O2).
5-((3-Chlorophenyl)amino)benzo[c][2,6]naphthyridine-8-carboxylic acid (cas: 1009820-21-6) belongs to naphthyridine derivatives. The naphthyridines have 10 delocalized π-electrons located in five molecular orbitals, each of which is distorted by the presence of the nitrogen atoms causing an electron drift in that direction. Halogen atoms attached to the naphthyridine moiety can be easily replaced by other nucleophiles such as alkoxides and amines.Formula: C19H12ClN3O2
Referemce:
1,8-Naphthyridine – Wikipedia,
1,8-Naphthyridine | C8H6N2 – PubChem