<?xml version="1.0" encoding="UTF-8"?><xml><records><record><source-app name="Biblio" version="7.x">Drupal-Biblio</source-app><ref-type>17</ref-type><contributors><authors><author><style face="normal" font="default" size="100%">Myrianthopoulos, V.a</style></author><author><style face="normal" font="default" size="100%">Kritsanida, M.a</style></author><author><style face="normal" font="default" size="100%">Gaboriaud-Kolar, N.a</style></author><author><style face="normal" font="default" size="100%">Magiatis, P.a</style></author><author><style face="normal" font="default" size="100%">Ferandin, Y.b</style></author><author><style face="normal" font="default" size="100%">Durieu, E.b</style></author><author><style face="normal" font="default" size="100%">Lozach, O.b</style></author><author><style face="normal" font="default" size="100%">Cappel, D.c</style></author><author><style face="normal" font="default" size="100%">Soundararajan, M.e</style></author><author><style face="normal" font="default" size="100%">Filippakopoulos, P.e</style></author><author><style face="normal" font="default" size="100%">Sherman, W.d</style></author><author><style face="normal" font="default" size="100%">Knapp, S.e</style></author><author><style face="normal" font="default" size="100%">Meijer, L.b f</style></author><author><style face="normal" font="default" size="100%">Mikros, E.a</style></author><author><style face="normal" font="default" size="100%">Skaltsounis, A.-L.a</style></author></authors></contributors><titles><title><style face="normal" font="default" size="100%">Novel inverse binding mode of indirubin derivatives yields improved selectivity for DYRK kinases</style></title><secondary-title><style face="normal" font="default" size="100%">ACS Medicinal Chemistry Letters</style></secondary-title></titles><keywords><keyword><style  face="normal" font="default" size="100%">article</style></keyword><keyword><style  face="normal" font="default" size="100%">binding affinity</style></keyword><keyword><style  face="normal" font="default" size="100%">binding site</style></keyword><keyword><style  face="normal" font="default" size="100%">bromine</style></keyword><keyword><style  face="normal" font="default" size="100%">carboxylic acid derivative</style></keyword><keyword><style  face="normal" font="default" size="100%">crystal structure</style></keyword><keyword><style  face="normal" font="default" size="100%">drug binding</style></keyword><keyword><style  face="normal" font="default" size="100%">drug design</style></keyword><keyword><style  face="normal" font="default" size="100%">drug screening</style></keyword><keyword><style  face="normal" font="default" size="100%">drug synthesis</style></keyword><keyword><style  face="normal" font="default" size="100%">dual specificity tyrosine phosphorylation regulated kinase</style></keyword><keyword><style  face="normal" font="default" size="100%">indirubin</style></keyword><keyword><style  face="normal" font="default" size="100%">indole derivative</style></keyword><keyword><style  face="normal" font="default" size="100%">molecular model</style></keyword><keyword><style  face="normal" font="default" size="100%">priority journal</style></keyword><keyword><style  face="normal" font="default" size="100%">protein kinase</style></keyword><keyword><style  face="normal" font="default" size="100%">structure activity relation</style></keyword><keyword><style  face="normal" font="default" size="100%">thermodynamics</style></keyword><keyword><style  face="normal" font="default" size="100%">unclassified drug</style></keyword></keywords><dates><year><style  face="normal" font="default" size="100%">2013</style></year></dates><urls><web-urls><url><style face="normal" font="default" size="100%">http://www.scopus.com/inward/record.url?eid=2-s2.0-84872355664&amp;partnerID=40&amp;md5=dbf5b380fe0fe884cb11e3f7a58d2555</style></url></web-urls></urls><number><style face="normal" font="default" size="100%">1</style></number><volume><style face="normal" font="default" size="100%">4</style></volume><pages><style face="normal" font="default" size="100%">22-26</style></pages><language><style face="normal" font="default" size="100%">eng</style></language><abstract><style face="normal" font="default" size="100%">DYRK kinases are involved in alternative pre-mRNA splicing as well as in neuropathological states such as Alzheimer’s disease and Down syndrome. In this study, we present the design, synthesis, and biological evaluation of indirubins as DYRK inhibitors with enhanced selectivity. Modifications of the bis-indole included polar or acidic functionalities at positions 5' and 6' and a bromine or a trifluoromethyl group at position 7, affording analogues that possess high activity and pronounced specificity. Compound 6i carrying a 5'-carboxylate moiety demonstrated the best inhibitory profile. A novel inverse binding mode, which forms the basis for the improved selectivity, was suggested by molecular modeling and confirmed by determining the crystal structure of DYRK2 in complex with 6i. Structure-activity relationships were further established, including a thermodynamic analysis of binding site water molecules, offering a structural explanation for the selective DYRK inhibition. © 2012 American Chemical Society.</style></abstract><notes><style face="normal" font="default" size="100%">cited By (since 1996)7</style></notes></record></records></xml>