Homepage » Research » Computer-aided drug design and computational chemistry on Nuclear Receptors and Kinases » Kinases


Kinase function is a collective biological determinant of normal cell life. The correlation between aberrant kinase activity and disease is now well established and abnormal kinase function is recognized as a milestone in the pathology of serious disease states like neurodegeneration, inflammatory responses, as well as various forms of cancer. As a result, kinases have emerged as highly attractive and well prioritized drug targets. R&D programs focusing on kinase inhibitors currently count up to the impressive 25% of total projects worldwide. To this end, efforts employing rational methods in the design of novel inhibitory compounds are undoubdfully favored in a generous fashion by SAR studies based on theoretical studies. Implemented methodologies fall into either of two categories, namely the structure-based approach involving sophisticated molecular simulations and dynamics and its corresponding ligand-based technique entailing both traditional QSAR as well as modern informatics tools and large-scale data analysis.
Our group is interested in the rationalization of the mechanisms underlying potency and selectivity of kinase inhibitors and their exploration for the discovery and targeted optimization of compounds as leads, chemical probes, or clinical candidate drugs targeting disease-relevant kinases. Current projects include the following targets:The dual-specificity DYRK family of kinases, relatively unexplored targets that are involved in apoptosis and development of the nervous system.
The Aurora family of mitotic kinases that constitute major pharmacological targets with respect to their involvement in cancer development.
The cancer-related enzyme Casein Kinase-1 as well as members -1, -2, and -9 of the family of CDKs.
The enzymes CDK5 and kinase GSK-3β that are recognized as key players in the pathology of neurodegenerative states like Alzheimer’s and Parkinson’s diseases.
In addition and in a collaborative manner, our group participates in projects focusing on the study of transmembrane proteins that belong either to the GPCR family of receptors or the MFS family of transporters.

Selected Publications

Myrianthopoulos, V., Kritsanida, M., Gaboriaud-Kolar, N., Magiatis, P., Ferandin, Y., Durieu, E., Lozach, O., Cappel, D., Soundararajan, M., Filippakopoulos, P., Sherman, W., Knapp, S., Meijer, L., Mikros, E., Skaltsounis, A.-L. Novel inverse binding mode of indirubin derivatives yields improved selectivity for DYRK kinases (2013) ACS Medicinal Chemistry Letters, 4 (1), pp. 22-26.
DOI: 10.1021/ml300207a

Xingi, E., Smirlis, D., Myrianthopoulos, V., Magiatis, P., Grant, K.M., Meijer, L., Mikros, E., Skaltsounis, A.-L., Soteriadou, K. 6-Br-5methylindirubin-3′oxime (5-Me-6-BIO) targeting the leishmanial glycogen synthase kinase-3 (GSK-3) short form affects cell-cycle progression and induces apoptosis-like death: Exploitation of GSK-3 for treating leishmaniasis (2009) International Journal for Parasitology, 39 (12), pp. 1289-1303.
DOI: 10.1016/j.ijpara.2009.04.005

Vougogiannopoulou, K., Ferandin, Y., Bettayeb, K., Myrianthopoulos, V., Lozach, O., Fan, Y., Johnson, C.H., Magiatis, P., Skaltsounis, A.-L., Mikros, E., Meijer, L. Soluble 3′,6-substituted indirubins with enhanced selectivity toward glycogen synthase kinase -3 alter circadian period (2008) Journal of Medicinal Chemistry, 51 (20), pp. 6421-6431.
DOI: 10.1021/jm800648y

Oumata, N., Bettayeb, K., Ferandin, Y., Demange, L., Lopez-Giral, A., Goddard, M.-L., Myrianthopoulos, V., Mikros, E., Flajolet, M., Greengard, P., Meijer, L., Galons, H. Roscovitine-derived, dual-specificity inhibitors of cyclin-dependent kinases and casein kinases 1 (2008) Journal of Medicinal Chemistry, 51 (17), pp. 5229-5242.
DOI: 10.1021/jm800109e

Myrianthopoulos, V., Magiatis, P., Ferandin, Y., Skaltsounis, A.-L., Meijer, L., Mikros, E. An integrated computational approach to the phenomenon of potent and selective inhibition of Aurora kinases B and C by a series of 7-substituted indirubins (2007) Journal of Medicinal Chemistry, 50 (17), pp. 4027-4037.
DOI: 10.1021/jm070077z

Polychronopoulos, P., Magiatis, P., Skaltsounis, A.-L., Myrianthopoulos, V., Mikros, E., Tarricone, A., Musacchio, A., Roe, S.M., Pearl, L., Leost, M., Greengard, P., Meijer, L. Structural Basis for the Synthesis of Indirubins as Potent and Selective Inhibitors of Glycogen Synthase Kinase-3 and Cyclin-Dependent Kinases (2004) Journal of Medicinal Chemistry, 47 (4), pp. 935-946.
DOI: 10.1021/jm031016d