Selectivity, Cocrystal Structures, and Neuroprotective Properties of Leucettines, a Family of Protein Kinase Inhibitors Derived from the Marine Sponge Alkaloid Leucettamine B.
作者： Tania Tahtouh , Jonathan M. Elkins , Panagis Filippakopoulos , Meera Soundararajan , Guillaume Burgy
DOI: 10.1021/JM301034U
关键词: Protein kinase A 、 CLK1 、 Biochemistry 、 DYRK1A 、 Kinase 、 DYRK1B 、 Protein-Serine-Threonine Kinases 、 Cyclin-dependent kinase 2 、 Chemistry 、 Tyrosine phosphorylation
摘要: DYRKs (dual specificity, tyrosine phosphorylation regulated kinases) and CLKs (cdc2-like are implicated in the onset development of Alzheimer’s disease Down syndrome. The marine sponge alkaloid leucettamine B was recently identified as an inhibitor DYRKs/CLKs. Synthesis analogues (leucettines) led to optimized product, leucettine L41. Leucettines were cocrystallized with DYRK1A, DYRK2, CLK3, PIM1, GSK-3β. selectivity L41 studied by activity interaction assays recombinant kinases affinity chromatography competition assays. These approaches revealed unexpected potential secondary targets such CK2, SLK, lipid kinase PIKfyve/Vac14/Fig4. displayed neuroprotective effects on glutamate-induced HT22 cell death. also reduced amyloid precursor protein-induced death cultured rat brain slices. unusual multitarget leucettines may account for their effects. This family inhibitors dese...
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Mansour Debdab, François Carreaux, Steven Renault, Meera Soundararajan, Oleg Fedorov, Panagis Filippakopoulos, Olivier Lozach, Lucie Babault, Tania Tahtouh, Blandine Baratte, Yasushi Ogawa, Masatoshi Hagiwara, Andreas Eisenreich, Ursula Rauch, Stefan Knapp, Laurent Meijer, Jean-Pierre Bazureau, Leucettines, a Class of Potent Inhibitors of cdc2-Like Kinases and Dual Specificity, Tyrosine Phosphorylation Regulated Kinases Derived from the Marine Sponge Leucettamine B: Modulation of Alternative Pre-RNA Splicing Journal of Medicinal Chemistry. ,vol. 54, pp. 4172- 4186 ,(2011) , 10.1021/JM200274D
A. Khoshnan, Activation of the I B Kinase Complex and Nuclear Factor- B Contributes to Mutant Huntingtin Neurotoxicity The Journal of Neuroscience. ,vol. 24, pp. 7999- 8008 ,(2004) , 10.1523/JNEUROSCI.2675-04.2004
George W. Chan, Seymour Mong, Mark E. Hemling, Alan J. Freyer, Priscilla H. Offen, Charles W. DeBrosse, Henry M. Sarau, John W. Westley, New leukotriene B4 receptor antagonist : leucettamine A and related imidazole alkaloids from the marine sponge Leucetta microraphis Journal of Natural Products. ,vol. 56, pp. 116- 121 ,(1993) , 10.1021/NP50091A016
Juan Manuel Domínguez, Ana Fuertes, Leyre Orozco, María del Monte-Millán, Elena Delgado, Miguel Medina, Evidence for Irreversible Inhibition of Glycogen Synthase Kinase-3β by Tideglusib Journal of Biological Chemistry. ,vol. 287, pp. 893- 904 ,(2012) , 10.1074/JBC.M111.306472
Daniela C Glatz, Dan Rujescu, Yesheng Tang, Frank J Berendt, Annette M Hartmann, Frank Faltraco, Carlyn Rosenberg, Christine Hulette, Kurt Jellinger, Harald Hampel, Peter Riederer, Hans‐J Möller, Athena Andreadis, Kerstin Henkel, Stefan Stamm, The alternative splicing of tau exon 10 and its regulatory proteins CLK2 and TRA2‐BETA1 changes in sporadic Alzheimer's disease Journal of Neurochemistry. ,vol. 96, pp. 635- 644 ,(2006) , 10.1111/J.1471-4159.2005.03552.X
Judit Ribas, Jacint Boix, Cell differentiation, caspase inhibition, and macromolecular synthesis blockage, but not BCL-2 or BCL-XL proteins, protect SH-SY5Y cells from apoptosis triggered by two CDK inhibitory drugs Experimental Cell Research. ,vol. 295, pp. 9- 24 ,(2004) , 10.1016/J.YEXCR.2003.12.019
Pedro Molina, Pedro Almendros, Pilar M. Fresneda, An iminophosphorane-mediated efficient synthesis of the alkaloid eudistomin U of marine origin Tetrahedron Letters. ,vol. 35, pp. 2235- 2236 ,(1994) , 10.1016/S0040-4039(00)76806-7
Marie Knockaert, Karen Wieking, Sophie Schmitt, Maryse Leost, Karen M. Grant, Jeremy C. Mottram, Conrad Kunick, Laurent Meijer, Intracellular Targets of Paullones. Identification following affinity purification on immobilized inhibitor. Journal of Biological Chemistry. ,vol. 277, pp. 25493- 25501 ,(2002) , 10.1074/JBC.M202651200
Isidro Ferrer, Marta Barrachina, Berta Puig, M. Martínez de Lagrán, Eulalia Martí, Jesús Avila, Mara Dierssen, Constitutive Dyrk1A is abnormally expressed in Alzheimer disease, Down syndrome, Pick disease, and related transgenic models. Neurobiology of Disease. ,vol. 20, pp. 392- 400 ,(2005) , 10.1016/J.NBD.2005.03.020
Richard M. Eglen, Terry Reisine, The Current Status of Drug Discovery Against the Human Kinome Assay and Drug Development Technologies. ,vol. 7, pp. 22- 43 ,(2009) , 10.1089/ADT.2008.164