1219127-01-1Relevant articles and documents
From Synthetic Simplified Marine Metabolite Analogues to New Selective Allosteric Inhibitor of Aurora B Kinase
Juillet, Charlotte,Ermolenko, Ludmila,Boyarskaya, Dina,Baratte, Blandine,Josselin, Béatrice,Nedev, Hristo,Bach, Stéphane,Iorga, Bogdan I.,Bignon, Jér?me,Ruchaud, Sandrine,Al-Mourabit, Ali
, p. 1197 - 1219 (2021/02/05)
Significant inhibition of Aurora B was achieved by the synthesis of simplified fragments of benzosceptrins and oroidin belonging to the marine pyrrole-2-aminoimidazoles metabolites isolated from sponges. Evaluation of kinase inhibition enabled the discovery of a synthetically accessible rigid acetylenic structural analogue EL-228 (1), whose structure could be optimized into the potent CJ2-150 (37). Here we present the synthesis of new inhibitors of Aurora B kinase, which is an important target for cancer therapy through mitosis regulation. The biologically oriented synthesis yielded several nanomolar inhibitors. The optimized compound CJ2-150 (37) showed a non-ATP competitive allosteric mode of action in a mixed-type inhibition for Aurora B kinase. Molecular docking identified a probable binding mode in the allosteric site "F"and highlighted the key interactions with the protein. We describe the improvement of the inhibitory potency and specificity of the novel scaffold as well as the characterization of the mechanism of action.
New adenosine receptor ligands and uses thereof
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Page/Page column 72-73, (2010/08/07)
The present invention provides new compounds with high affinity for adenosine A2A receptors. It also provides antagonists of adenosine A2A receptors and their use as medicaments for the treatment and/or prophylaxis of diseases and di
