GSK-3 Allosteric Modulation Cavities:
Abstract
Glycogen synthase kinase 3 (GSK-3)
is an important drug target for human severe unmet diseases.
Discovery and/or design of allosteric kinase modulators are gaining importance in this field not only for the increased selectivity of this kind of compounds but also for the subtle modulation of the target.
This last point is of utmost importance for the GSK-3 inhibition as a therapeutic approach.
GSK-3 activity is completely necessary for life,
and only the aberrant overactivity found in the pathologies should be inhibited with its inhibitors treatment.
We performed here a search for the druggable sites on the enzyme using the fpocket algorithm with the aim to provide allosteric potential binding sites on it and new clues for further drug discoveries.
Moreover, our results allowed us to determine the binding sites of different GSK-3 ATP noncompetitive inhibitors,
such as manzamine A and the new small molecule VP 0.7, providing evidence for potential allosteric inhibition of GSK-3.
Citing Articles
View all 14 citing articlesCitation data is made available by participants in CrossRef's Cited-by Linking service. For a more comprehensive list of citations to this article, users are encouraged to perform a search in SciFinder.
This article has been cited by 6 ACS Journal articles (5 most recent appear below).
Crosstalk between Phosphodiesterase 7 and Glycogen Synthase Kinase-3: Two Relevant Therapeutic Targets for Neurological Disorders
Jose A. Morales-Garcia, Valle Palomo, Miriam Redondo, Sandra Alonso-Gil, Carmen Gil, Ana Martinez, and Ana Perez-CastilloACS Chemical Neuroscience2014 5 (3), 194-204Crosstalk between Phosphodiesterase 7 and Glycogen Synthase Kinase-3: Two Relevant Therapeutic Targets for Neurological Disorders
Jose A.Morales-Garcia, VallePalomo, MiriamRedondo, SandraAlonso-Gil, CarmenGil, AnaMartinez, and AnaPerez-CastilloACS Chemical Neuroscience2014 5 (3), 194-204Chronic neuroinflammation has been increasingly recognized as a primary mechanism underlying acute brain injury and neurodegenerative diseases. Enhanced expression of diverse pro-inflammatory agents in glial cells has been shown to contribute to the cell ...
Glycogen Synthase Kinase-3 Inhibitors as Potent Therapeutic Agents for the Treatment of Parkinson Disease.
J. A. Morales-García, C. Susín, S. Alonso-Gil, D. I. Pérez, V. Palomo, C. Pérez, S. Conde, A. Santos, C. Gil, A. Martínez, and A. Pérez-CastilloACS Chemical Neuroscience2013 4 (2), 350-360Glycogen Synthase Kinase-3 Inhibitors as Potent Therapeutic Agents for the Treatment of Parkinson Disease.
J. A.Morales-García, C.Susín, S.Alonso-Gil, D. I.Pérez, V.Palomo, C.Pérez, S.Conde, A.Santos, C.Gil, A.Martínez, and A.Pérez-CastilloACS Chemical Neuroscience2013 4 (2), 350-360Parkinson's disease (PD) is a devastating neurodegenerative disorder characterized by degeneration of the nigrostriatal dopaminergic pathway. Because the current therapies only lead to temporary, limited improvement and have severe side effects, new ...
Strategies for the Selective Regulation of Kinases with Allosteric Modulators: Exploiting Exclusive Structural Features
Zhizhou Fang, Christian Grütter, and Daniel RauhACS Chemical Biology2013 8 (1), 58-70Strategies for the Selective Regulation of Kinases with Allosteric Modulators: Exploiting Exclusive Structural Features
ZhizhouFang, ChristianGrütter, and DanielRauhACS Chemical Biology2013 8 (1), 58-70The modulation of kinase function has become an important goal in modern drug discovery and chemical biology research. In cancer-targeted therapies, kinase inhibitors have been experiencing an upsurge, which can be measured by the increasing number of ...
Glycogen Synthase Kinase 3 Inhibition Promotes Adult Hippocampal Neurogenesis in Vitro and in Vivo
Jose A. Morales-Garcia, Rosario Luna-Medina, Sandra Alonso-Gil, Marina Sanz-SanCristobal, Valle Palomo, Carmen Gil, Angel Santos, Ana Martinez, and Ana Perez-CastilloACS Chemical Neuroscience2012 3 (11), 963-971Glycogen Synthase Kinase 3 Inhibition Promotes Adult Hippocampal Neurogenesis in Vitro and in Vivo
Jose A.Morales-Garcia, RosarioLuna-Medina, SandraAlonso-Gil, MarinaSanz-SanCristobal, VallePalomo, CarmenGil, AngelSantos, AnaMartinez, and AnaPerez-CastilloACS Chemical Neuroscience2012 3 (11), 963-971Glycogen synthase kinase-3 (GSK-3) is a serine/threonine kinase originally identified as a regulator of glycogen metabolism but it also plays a pivotal role in numerous cellular functions, including differentiation, cell cycle regulation, and ...
Targeting GSK3 from Ustilago maydis: Type-II Kinase Inhibitors as Potential Antifungals
Christian Grütter, Jeffrey R. Simard, Svenja C. Mayer-Wrangowski, Peter H. Schreier, José Pérez-Martín, André Richters, Matthäus Getlik, Oliver Gutbrod, Christoph A. Braun, Michael E. Beck, and Daniel RauhACS Chemical Biology2012 7 (7), 1257-1267
0 件のコメント:
コメントを投稿