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Human CK2 catalytic domain in complex with a benzopyridoindole derivative inhibitorHuman CK2 catalytic domain in complex with a benzopyridoindole derivative inhibitor
Structural highlights
Publication Abstract from PubMedThe alkyloid compound ellipticine derived from the berrywood tree is a topoisomerase II poison that is used in ovarian and breast cancer treatment. In this study, we report the identification of ellipticine derivatives and their tetracyclic angular benzopyridoindole analogues as novel ATP-competitive inhibitors of the protein kinase CK2. In vitro and in vivo assays showed that these compounds have a good pharmacologic profile, causing a marked inhibition of CK2 activity associated with cell cycle arrest and apoptosis in human cancer cells. Further, in vivo assays demonstrate antitumor activity in a mouse xenograft model of human glioblastoma. Finally, crystal structures of CK2-inhibitor complex provide structural insights on the molecular basis of CK2 inhibition. Our work lays the foundation for development of clinically useful CK2 inhibitors derived from a well-studied scaffold with suitable pharmacokinetics parameters. Cancer Res; 70(23); 9865-74. (c)2010 AACR. Antitumor Activity of Pyridocarbazole and Benzopyridoindole Derivatives that Inhibit Protein Kinase CK2.,Prudent R, Moucadel V, Nguyen CH, Barette C, Schmidt F, Florent JC, Lafanechere L, Sautel CF, Duchemin-Pelletier E, Spreux E, Filhol O, Reiser JB, Cochet C Cancer Res. 2010 Dec 1;70(23):9865-74. Epub 2010 Nov 30. PMID:21118972[1] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See AlsoReferences
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