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Summary:
Protein kinases are
targets for treatment of a number of diseases. Kinase structures have informed drug design and
have illuminatedP Pthe mechanism of inhibition. In fact, they have
providedP Pinsights
into targeting the inactive or active form of the kinase,P Pfor
targeting the global constellation of residues at the ATPP Psite
or less conserved additional pockets or single residues,P Pand
into targeting noncatalytic domains. Our laboratory works applying both direct structure-based
drug design (SBDD) and indirect quantitative structure-activity relationship (QSAR)
approaches to discover and optimize new potent and selective kinase inhibitors. Novel
strategies for developing human Aurora A, casein
kinase 1 (CK1) and 2 (CK2), and MEK inhibitors such as virtual libraries design, high throughput docking,
synthesis of parallel focused libraries and their biological screening are carrying out in our laboratories.
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Selected References:
Pagano MA, Poletto G, Di
Maira G, Cozza G, Ruzzene M, Sarno S, Bain J, Elliott M, Moro S, Zagotto G, Meggio F, Pinna LA. “Tetrabromocinnamic Acid
(TBCA) and Related Compounds Represent a New Class of Specific Protein Kinase
CK2 Inhibitors.” Chembiochem. 8, 129-139 (2006)
G. Cozza, P. Bonvini, E. Zorzi, G. Poletto, M.A. Pagano, S. Sarno, A. Donella-Deana, G. Zagotto, A. Rosolen, L.A. Pinna, F. Meggio, S. Moro “Identification of ellagic acid as potent inhibitor of protein kinase CK2: a successful example of a virtual screening application.” J. Med. Chem. 49, 2363-2366 (2006)
S. Moro, F. Varano, G. Cozza, M. A. Pagano, G. Zagotto, A. Chilin, A. Guiotto, D. Catarzi, V. Calotta, L. A. Pinna, F. Meggio “Pyrazoloquinazoline tricyclic system as novel scaffold to design new kinase CK2 inhibitors”. Letter in Drug Design & Discov. 3, 281-284 (2006)
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