Tools
Wednesday, 19th June, 2013
Structure-Based Drug Design conference
BIO-IT, 19-21 June 2013, Cambridge, Massachusetts, USA.
Speaker: Fabritiis De, G
Monday, 3rd June, 2013
Conference of the Russian Biophysical society
3-7 June 2013, Moscow, Russia.
Speaker: Fabritiis De, G
Monday, 8th April, 2013
Conference of the american chemical society
8-11 April 2013 New Orleans,USA.
Speaker: Fabritiis De, G
Monday, 25th March, 2013
Biomolecular Simulation 2013
25-27 March 2013, Nottingham, UK.
Speaker: Fabritiis De, G
Friday, 15th March, 2013, 12.00-13.00
Using docking and molecular dynamics to design drugs
We have discovered by high-throughput fragment-based docking several novel chemotypes of potent (single-digit nanomolar) and selective tyrosine kinase inhibitors [1-4]. Explicit solvent molecular dynamics has played an important role for the in silico validation of binding modes and the selection of compounds for testing in vitro. Definitive validation of the binding mode has been obtained by X-ray crystallography in our group [1,2]. The most advanced of our tyrosine kinase inhibitors are active on a subset of the NCI 60 cancer cell lines. Furthermore, some of our inhibitors have shown good pharmacokinetic properties in mice (including oral bioavailability) and are being currently selected for testing in tumor xenograft models. [1] K. Lafleur et al. Structure-based Optimization of Inhibitors of the Tyrosine Kinase EphB4. Part 2: Cellular Potency Improvement and Binding Mode Validation by X-ray Crystallography. J. Med. Chem. 56, 84, 2013. [2] H. Zhao, J. Dong, K. Lafleur, C. Nevado, and A. Caflisch. Discovery of a novel chemotype of tyrosine kinase inhibitors by fragment-based docking and molecular dynamics. ACS Med. Chem. Lett. 3, 834, 2012. [3] H. Zhao, D. Huang, and A. Caflisch. Discovery of tyrosine kinase inhibitors by docking into an inactive kinase conformation generated by molecular dynamics. ChemMedChem 7, 1983, 2012. [4] K. Lafleur et al. Structure-based optimization of potent and selective inhibitors of the tyrosine kinase erythropoietin producing human hepatocellular carcinoma receptor B4 (EphB4). J. Med. Chem. 52, 6433, 2009.
Speaker: Amedeo Caflisch, Computational Structural Biology, University of Zurich, Switzerland.
Room Seminar room 473.10
Monday, 4th February, 2013
Fragment based drug discovery by simulation
CDDD - Computationally Driven Drug Discovery, Istituto Italiano di Tecnologia (IIT), Geneve (Italy) 4-6 February 2013
Speaker: Fabritiis De, G
Friday, 25th January, 2013, 12.00
Structural Bioinformatics applied to Bio-Nanotechnology
Speaker: Fernando Danilo González Nilo, Center for Bioinformatics and Integrative Biology (CBIB), Santiago de Chile, Chile.
Room Marie Curie
Wednesday, 26th September, 2012
Fragment based drug discovery by simulation
Drug Design 2012, Oxford, UK, 26-28 September, 2012
Speaker: Fabritiis De, G
Friday, 13th July, 2012, 11:00-12:00
Multitarget strategies in the search of novel drug candidates for the treatment of Alzheimer’s disease
Alzheimer’s disease (AD) is a disruptive brain disorder characterized by a massive neuronal loss leading to a progressive decline of cognitive function. The cause of AD is poorly understood. Several hypotheses have been proposed over the years to explain the disease and to identify relevant drug targets. It has been shown that AD is always associated with the formation of plaques (amyloid hypothesis) as well as with the deposition of neurofibrillary tangles (tau hypothesis). There are few currently approved drugs, and these offer just a small benefit for a relatively short period of time. Nowadays, AD represents the largest unmet medical need in neurology. Our approach to drug discovery in AD has been based on a radical change of the classical ‘one-drug one-target’ paradigm into a multitarget drug discovery approach. In this seminar, two different series of molecules discovered following the multitarget strategy will be presented. The initial steps of our drug discovery strategy will be discussed, from structure-based drug design, carried out by means of computational tools, to chemical syntheses, and in vitro and in vivo characterization.
Speaker: Dr. Andrea Cavalli, Italian Institute of Technology (IIT), Genova, Italy
Room Xipre (seminar 173.06-183.01)
Tuesday, 5th June, 2012
Molecular recognition by simulations
2nd Aegean Conference on Molecular Recognition, Rodos Palace Conference Center, Ixia, Rhodes, Greece, 5-10 June 2012.
Speaker: Fabritiis De, G
