[Colloquium] Seminar Announcement: Multitargeted pharmaceuticals: from occasional findings to rational discoveries

[Ninfa Mayorga]

~Reminder~

Computation Institute Presentation 

Speaker: Vladimir Poroikov, Institute of Biomedical Chemistry of Rus. Acad. Med. Sci., Moscow, Russia
Host:  Andrey Rzhetsky
Date: May 9, 2012
Time: 1:00 PM - 2:00 PM
Location: University of Chicago, Searle 240A, 5735 S. Ellis Avenue

Multitargeted pharmaceuticals: from occasional findings to rational discoveries

ABSTRACT:
Many diseases have a complex etiology, which treatment often requires multiple actions on several pharmacological targets. On the contrary, the majority of current drugs were designed to interact with a single target, which sometimes leads to activation/blockade of other elements in the appropriate signal regulatory pathway. As a consequence of negative feedbacks, expected pharmacotherapeutic effect may be significantly decreased or even completely suppressed. Therefore, the multitargeted drugs, due to their additive, synergistic or antagonistic action, might have some advantages comparing to the monotargeted medicines. The purpose of our study was to develop computer-assisted methods for identification of the most promising targets; finding and rational design of multitargeted agents with the required biological activity profiles. 

The following computer-aided tools were used in this work. Net2Drug-software for simulation of behavior of signal regulatory pathways and identification of the most promising targets and their combinations. PASS (Prediction of Activity Spectra for Substances,http://pharmaexpert.ru/passonline/)-software, which predicts about 4000 kinds of biological activity on the basis of structural formula with mean accuracy about 95%. PharmaExpert-software for analysis of PASS predicted biological activity spectra and selection of compounds with the required biological activity profiles. 

Case study. We identified the promising targets for treatment of cancers by analysis of signal regulatory pathways. Based on computer prediction of biological activity for 24 mln chemical compounds, 64 probable multitargeted antineoplastic agents were selected for experimental testing. 11 samples were tested in cell culture assays. Antineoplastic activity was confirmed experimentally in two molecules (one was active against breast cancer and another-against melanoma cell lines). Therefore, computer-aided methods were shown to be quite useful in discovery of novel pharmacological targets and their ligands.

More applications will be presented and current trends for finding and rational design of new multitargeted pharmaceutical agents will be discussed.

Acknowledgements. This work was partially supported by European Commission FP6 grant LSHB-CT-2007-037590 (Net2Drug), FP7 grant 200787 (OpenTox), ISTC grants 3197 and 3777, RFBR grants 05-07-90123 and 06-03-08077.
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Prof. Vladimir Poroikov is currently the Head of Department for Bioinformatics and Laboratory for Structure-Function Based Drug Design at the Orekhovich Institute of Biomedical Chemistry of Russian Academy of Medical Sciences, and Professor of Medical & Biological Faculty at the Russian State Medical University (Moscow, Russia). After graduation of Physical Faculty of the Lomonosov Moscow State University in 1974-1995 he worked at the National Research Center for Biologically Active Compounds (NRC BAC), Staraya Kupavna (Moscow Region). In 1981 he completed his Ph.D. in Biophysics at the Engelhardt Institute of Molecular Biology under supervision of Prof. Vladimir Tumanyan. In 1995 he completed his Dr. Sci. in Pharmacology at the NRC BAC. His scientific interests include bioinformatics, chemoinformatics, (Q)SAR, molecular modelling and computer-aided drug design & discovery. Prof. Poroikov is a co-author of over 180 papers published in peer-reviewed journals and monographs, 11 computer programs and databases registered by Russian Patent Agency, and 12 non-open published reports in R&D of new pharmaceuticals. He is a Member of Editorial Board of a few scientific journals including Biomedical Chemistry, Pharmaceutical Chemistry Journal, SAR and QSAR in Environmental Research; reviewer of Bioorganic and Medicinal Chemistry, PNAS, Molecular Informatics, Journal of Proteomics, Journal of Bioinformatics and Computational Biology, Mini-reviews in Medicinal Chemistry, and others; Chairman of the Russian Section of the Cheminformatics and QSAR Society; Member of the American Chemical Society; Member of the Organizing Committees and/or invited speaker of more than 10 International conferences during the past 3 years. Prof. Poroikov is a winner of AstraZeneca 'Avangard of Knowledge - 2011' competition; he was awarded by Diploma and Medal of the Six Moscow International Congress 'Biotechnology: State of the Art and Prospects of Development' (2011), Gold Awar d of the International Foundation 'Scientific Partnership' (2010), Diploma of Cambridge Biographic Institute (Leading Scientist in Bioinformatics and Computer-Aided Drug Discovery, 2005), Diploma of Russian Academy of Medical Sciences (2004), Special Russian Academy of Sciences Grant for Outstanding Russian Scientists (2001-2003), Gold Medal 'For Scientific Partnerships' (2001), Medal "850 Years of Moscow' (1997). His works are widely cited in International scientific literature (898 citations, h-index=17).

More information is available at: http://scipeople.ru/users/5310286/

Vladimir Poroikov
Institute of Biomedical Chemistry of Russia Academy Medical Sciences, Moscow, Russia
E-mail: vladimir.poroikov at ibmc.msk.ru

Lunch will be provided


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