Ontario Institute for Cancer Research, Drug Discovery Program ... Research Scientist and Manager, Computational Chemistry and Cheminformatics at.
Meet Our Editorial Board Member
Current Drug Discovery Technologies, 2015, Vol. 12, No. 4
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Meet Our Editorial Board Member Prof. Dr. Gennady Poda
Ontario Institute for Cancer Research, Drug Discovery Program 661 University Avenue, Suite 510 Toronto, Ontario, Canada Dr. Gennady Poda, an expert in computational drug discovery, is Principal Research Scientist and Manager, Computational Chemistry and Cheminformatics at the Ontario Institute for Cancer Research and an Assistant Professor (status only) at the Leslie Dan Faculty of Pharmacy, University of Toronto. Poda is a native of Ukraine and obtained a Master of Science degree in Molecular and Chemical Physics at the renowned Moscow Institute of Physics and Technology (MIPT). He then earned a PhD in Bioorganic Chemistry from the Institute for Bioorganic and Gennady Poda Petrochemistry, National Academy of Sciences in Kyiv, Ukraine. His specialities include computer-aided drug design covering all aspects of modern computational drug discovery: structure-, ligandand fragment-based drug discovery, cheminformatics, data mining and analysis, physical and ADMET (absorption, distribution, metabolism, excretion and toxicity) property prediction. Poda has used his strong background in physics, mathematics and computing to model protein-ligand interactions with mathematical precision. Some of his earliest work was in the area of opioid research. Poda built three-dimensional models of the three major subtypes of opioid receptors that were used to design more potent opioid analgesics. The models helped to provide an understanding of the molecular mechanisms of action for drugs such as cocaine, morphine and other opioids. The models developed through his collaboration with Prof. Philip Portoghese’s group provided evidence led to the successful design of an opioid agonist of unprecedented potency. Poda has pioneered an ensemble machine learning approach and its use in artificial neural networks (ANN) emphasizing the necessity of randomized initial weights to overcome local minima during the training stage. While he was Senior Principal Scientist at Pfizer’s St. Louis Research Laboratories, Poda made major contributions to late-stage pre-clinical discovery of drug leads in multiple therapeutic areas including disease-modifying antirheumatic drugs (DMARDs), antithrombotics, CNS analgesic, inhaled chronic obstructive pulmonary disease (COPD) drug candidates and anti-cancer agents. One of his projects led to the development of a pre-clinical drug candidate for the treatment of rheumatoid arthritis, a highly potent MK2 inhibitor with unprecedented selectivity against protein kinases involved in the cell cycle. This resulted in four patents, one publication in the Journal of Medicinal Chemistry and two in Bioorganic and Medicinal Chemistry Letters. Poda’s work in the structure-based design of TF/fVIIa led to development of another pre-clinical candidate for the treatment of deep vein thrombosis (DVT). This work was published in Bioorganic and Medicinal Chemistry Letters. His impactful work in collaboration with Dr. Igor Tetko in the prediction of physical properties of drug candidates, such as octanol-water partition coefficient, resulted in highly cited publications in the Journal of Medicinal Chemistry, Journal of Pharmaceutical Sciences and Drug Discovery Today, along with a book chapter. His work on structural alerts for toxic chemicals and compounds with potential adverse reactions led to development of the ToxAlerts web server and a publication in the Journal of Chemical Information and Modeling. Since joining OICR, Poda has been involved in a number of productive collaborations with scientists at the University of Toronto, the Structural Genomics Consortium and Industry. A collaboration with Prof. Andrei Yudin from the University of Toronto focussed on the molecular simulation of cyclization of oligoproline macrocycles led to a publication in Chemistry – A European Journal. Another effort initiated by Dr. Rima Al-awar, Director, Drug Discovery Program, OICR, with the SGC led to the discovery of several novel, potent, selective, drug-like inhibitors of key enzymes responsible for epigenetics reprogramming of genes that are responsible for aggressive acute mixed-lineage leukemia (MLL). This work was published in Biochemical Journal, Structure as well as ACS Medicinal Chemistry Letters. In addition, Poda designed a chemical probe called OICR-9429 that disrupts WDR5-MLL interactions.
192 Current Drug Discovery Technologies, 2015, Vol. 12, No. 4
Meet Our Editorial Board Member
Research by two external groups has shown this probe to be effective in stopping cancer cell growth in breast cancer cell lines and a specific subtype of leukemia cells (published in Nature Chemical Biology and Nature). Further collaborative projects within the Toronto Discovery District led to an understanding of the mechanism of action of the hydroxyl-aryl-aldehyde class of IRE1 endonuclease inhibitors (Nature Communications), and the therapeutic potential of human Kallikrein-related serine peptidases (Nature Reviews Drug Discovery). Poda also helped develop small molecule drug candidates for the treatment of haematological cancers that are being further developed through a partnership with OICR, the University Health Network, Novera Therapeutics and Johnson & Johnson Innovation (C$450 million agreement). Poda was recipient of the Pfizer Team Award from the President of PGRD and multiple Individual Performance Awards. A poster by Poda was recognized as a Top 10 poster at Pfizer Tech 2006 Conference. He is author and co-author of 52 publications in peer-reviewed journals, two book chapters and four patents. Dr. Poda was recently a recipient of the OICR Extra Mile Award and two Innovative Spirit Awards in recognition of his structure-based and cheminformatics support of several on-going projects within OICR’s Drug Discovery Program. SELECTED PUBLICATIONS [1]
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Grebien F, Vedadi M, Getlik M, Giambruno R, Grover A, Avellino R, Vittori S, Kuznetsova E, Smil D, BarsyteLoverjoy D, Li F, Poda G, Schapira M, Wu H, Dong A, Senistera G, Schonegger A, Bilban M, Bock C, Brown PJ, Zuber J, Bennett K, Al-awar R, Delwel R, Nerlov C, Arrowsmith CH, Superti-Furga G. C/EBPa N-Terminal Leukemia is Sensitive to Pharmacological Targeting of the WDR5-MLL Interaction. Nat Chem Biol 2015; 11(8): 571-8. Prassas I, Eissa A, Poda G, Diamandis EP. Unleashing the Therapeutic Potential of Human Kallikrein-Related Serine Peptidases. Nat Rev Drug Disc 2015; 14: 183-202. Sanches M, Duffy N, Talukdar M, Thevakumaran N, Chiovitti D, Canny M, Lee K, Kourinov I, Uehling D, Al-awar R, Poda G, Prakesch M, Wilson B, Tam V, Schweitzer C, Toro A, Lucas JL, Vuga D, Lehmann L, Durocher D, Zeng Q, Patterson JB, Sicheri F. Structure and Mechanism of Action of the Hydroxy-Aryl-Aldehyde Class of IRE1 Endonuclease Inhibitors. Nat Commun 2014; 5: 4202. Senisterra G, Wu H, Allali-Hassani A, Wasney GA, Barsyte-Lovejoy D, Dombrovsky L, Dong A, Nguyen KT, Smil D, Bolshan Y, Hajian T, He H, Seitova A, Chau I, Li F, Poda G, Couture JF, Brown PJ, Al-awar R, Schapira M, Arrowsmith CH, Vedadi M. Small Molecule Inhibition of MLL Activity by Distribution of Its Interaction with WDR5. Biochem J 2013; 449: 151-9. Scully CCG, Rai V, Poda G, Zaretsky S, Burns DC, Houliston SR, Lou T, Yudin A. Bending Rigid Molecular Rods: Formation and Properties of Oligoproline Marcocycles. Chemistry 2012; 18: 15612-7. Sushko I, Salmina E, Potemkin V, Poda G, Tetko IV. ToxAlerts: a Web Server of Structural Alerts for Toxic Chemicals and Compounds with Potential Adverse Reactions. J Chem Inf Mod 2012; 52(8): 2310-6. Siarheyeva A, Senisterra G, Allali-Hassani A, Dong A, Dobrovetsky E, Wasney GA, Chau I, Marcellus R, Hajian T, Liu F, Korboukh I, Smil D, Bolshan Y, Min J, Wu H, Zeng H, Loppnau P, Poda G, Griffin C, Aman A, Brown PJ, Jin Ji, Alawar R, Arrowsmith CH, Schapira M, Vedadi M. A Novel Allosteric Inhibitor of Arginine Methyltransferase PRMT3. Structure 2012; 20(8): 1425-35. Anderson DR, Meyers MJ, Kurumbail RG, Caspers N, Poda G, Long S, Pierce B, Mahoney MW, Mourey RJ. Benzothiophene Inhibitors of MK2: Part 1. Structure-Activity Relationships, Assessments of Selectivity and Cellular Potency. Bioorg Med Chem Lett 2009; 19(16): 4878-81. Anderson DR, Meyers MJ, Kurumbail RG, Caspers N, Poda G, Long S, Pierce B, Mahoney MW, Parikh M, Mourey RJ. Benzothiophene Inhibitors of MK2: Part 2. Improvements in Kinase Selectivity and Cell Potency. Bioorg Med Chem Lett 2009; 19(16): 4882-4. Mannhold R, Poda G, Ostermann C, Tetko IV. Calculation of molecular lipophilicity: State-of-the-art and comparison of Log P methods on more than 96,000 compounds. J Pharm Sci 2009; 98: 861-93. Anderson DR, Meyers MJ, Vernier WF, Mahoney MW, Kurumbail RG, Caspers N, Poda G, Schindler JF, Reitz DB, Mourey RL. Pyrrolopyridine Inhibitors of Mitogen-Activated Protein Kinase-Activated Protein Kinase 2 (MK-2). J Med Chem 2007; 50(11): 2647-54. Tetko IV, Bruneau P, Mewes HW, Rohrer DC, Poda G. Can we estimate the accuracy of ADME-Tox predictions? Drug Discov Today 2006; 11(15): 700-7. Schweitzer BA, Neumann WL, Rahman H, Kusturin CL, Sample KR, Poda G, Kurumbail RG, Stevens AM, Stegeman RA, Stallings WC, South MS. Structure-Based Design and Synthesis of Pyrazinones Containing Novel P1 ‘Side Pocket’ Moieties as Inhibitors of TF/VIIa. Bioorg Med Chem Lett 2005; 15(12): 3006-11. Tetko IV, Poda G. Application of ALOGPS 2.1 to predict log D distribution coefficient for Pfizer proprietary compounds. J Med Chem 2004; 47(23): 5601-4. Tetko IV, Luik AI, Poda G. Applications of Neural Networks in Structure-Activity Relationships of a Small Number of Molecules. J Med Chem 1993; 36(7): 811-4.
