个人简介

B.Sc. (McGill University, 1977) M.Sc. (McGill University, 1979) Ph.D. (McGill University, 1990) Postdoctoral Fellow (Brown University, 1991)

研究领域

Chemical Biology Synthesis/Catalysis

Our projects focus on the design and synthesis of small molecule ligands that can bind to mammalian or microbial targets modulating their function. Our main objective is to design chemical tools that can facilitate investigations into the biological role of proteins associated with a disease state. Currently, a number of our projects involve structure-based ligand design targeting the human enzyme farnesyl pyrophosphate synthase (hFPPS). A key objective of these projects is to synthesize novel active site or allosteric site inhibitors of hFPPS that could potentially serve as “leads” for the design of better therapeutic agents for the treatment of osteoporosis, cancer and viral infections. However, the ultimate goal of these studies is to provide greater insight into the biological significance of post-translational prenylation of proteins and elucidate the role of hFPPS in the innate immune response during viral infections.

近期论文

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Cyrus M. Lacbay, John Mancuso, Yih-Shyan Lin, Nicholas Bennett, Matthias Gotte and Youla S. Tsantrizos. Modular Assembly of Purine-Like Bisphosphonates as Inhibitors of HIV-1 Reverse Transcriptase. J. Med. Chem. 2014, ASAP Yongda Zhang , Bruce Z. Lu , Guisheng Li, Sonia Rodriguez , Jonathan Tan , Han-Xun Wei, Jianxiu Liu, Frank Roschangar, Fei Ding, Wenyi Zhao, Bo Qu, Diana Reeves, Nelu Grinberg, Heewon Lee, Golo Heckmann, Oliver Niemeier, Michael Brenner, Youla Tsantrizos, Pierre L. Beaulieu, Azad Hossain, Nathan Yee, Vittorio Farina , and Chris H. Senanayake A Highly Concise and Convergent Synthesis of HCV Polymerase Inhibitor Deleobuvir (BI 207127): Application of a One-Pot Borylation–Suzuki Coupling Reaction. Org. Lett. 2014, ASAP LeeD.Fader, RebekahCarson, Seb́astienMorin, Franco̧isBilodeau, CatherineChabot, TedHalmos, Murray D. Bailey, Stephen H. Kawai, René Coulombe, Steven Laplante, Kevork Mekhssian, Araz Jakalian, Michel Garneau, Jianmin Duan, Stephen W. Mason, Bruno Simoneau, Craig Fenwick, Youla Tsantrizos, and Christiane Yoakim. Minimizing the Contribution of Enterohepatic Recirculation to Clearance in Rat for the NCINI Class of Inhibitors of HIV ACS Med. Chem. Lett., 2014, 5, 711–716 LeeD.Fader,*EricMalenfant,MathieuParisien, RebekahCarson, Franco̧isBilodeau, SergeLandry, MarcPesant, ChristianBrochu, Seb́astienMorin, CatherineChabot, TedHalmos, YvesBousquet, Murray D. Bailey, Stephen H. Kawai, René Coulombe, Steven LaPlante, Araz Jakalian, Punit K. Bhardwaj, Dominik Wernic, Patricia Schroeder, Ma'an Amad, Paul Edwards, Michel Garneau, Jianmin Duan, Michael Cordingley, Richard Bethell, Stephen W. Mason, Michael Bös, Pierre Bonneau, Marc-André Poupart, Anne-Marie Faucher, Bruno Simoneau, Craig Fenwick, Christiane Yoakim, and Youla Tsantrizos.* Discovery of BI 224436, a Noncatalytic Site Integrase Inhibitor (NCINI) of HIV‐1 ACS Med. Chem. Lett. 2014, 5, 422−427 Craig Fenwick,* Máan Amad, Murray D. Bailey, Richard Bethell, Michael Bös,* Pierre Bonneau, Michael Cordingley, René Coulombe, Jianmin Duan, Paul Edwards, Lee D. Fader, Anne-Marie Faucher, Michel Garneau, Araz Jakalian, Stephen Kawai, Louie Lamorte, Steven LaPlante, Laibin Luo, Steve Mason,* Marc-André Poupart,* Nathalie Rioux, Patricia Schroeder, Bruno Simoneau, Sonia Tremblay, Youla Tsantrizos,* Myriam Witvrouw, Christiane Yoakim. Preclinical Profile of BI 224436, a Novel HIV-1 Non-Catalytic-Site Integrase Inhibitor Antimicrob. Agents Chemother. 2014, 58, 3233-3244 Jaeok Park, Alexios N. Matralis, Albert M. Berghuis and Youla S. Tsantrizo.s* Human isoprenoid synthase enzymes as therapeutic targets Front. Chem. 2014, 2, 5764−5776 Joris W. De Schutter, Jaeok Park, Chun Yuen Leung, Patrick Gormley, Yih-Shyan Lin, Zheping Hu, Albert M. Berghuis, Judes Poirier, and Youla S. Tsantrizos.* Multistage Screening Reveals Chameleon Ligands of the Human Farnesyl Pyrophosphate Synthase: Implications to Drug Discovery for Neurodegenerative Diseases J. Med. Chem. 2014, 57, 5764−5776 Steven R. LaPlante,* Michael Bos, Christian Brochu, Catherine Chabot, Rene Coulombe, James R. Gillard, Araz Jakalian, Martin Poirier, Jean Rancourt, Timothy Stammers, Bounkham Thavonekham, Pierre L. Beaulieu, George Kukolj, Youla S. Tsantrizos* Conformation-Based Restrictions and Scaffold Replacements in the Design of HCV Polymerase Inhibitors: Discovery of Deleobuvir (BI 207127) J. Med. Chem. 2013, Ahead of Print; Manuscript ID: jm-2013-011862 Chun Yuen Leung, Jaeok Park, Joris W. De Schutter, Michael Sebag, Albert M. Berghuis, Youla S. Tsantrizos* Thienopyrimidine Bisphosphonate (ThPBP) Inhibitors of the Human Farnesyl Pyrophosphate Synthase – Optimization and Characterization of the Mode of Inhibition. J. Med. Chem. 2013, 56, 7939-7950 C.-Y. Leung, A. M. Langille, J. Mancuso, Y. S. Tsantrizos* Discovery of thienopyrimidine-based inhibitors of the human farnesyl pyrophosphate synthase – Parallel synthesis of analogs via a trimethylsilyl ylidene intermediate. Bioorg. Med. Chem. 2013, 21, 2229-2240 T.A. Stammers, * R. Coulombe, J. Rancourt, B. Thavonekham, G. Fazal, S. Goulet, A. Jakalian, D. Wernic, Y. S. Tsantrizos, M.-A. Poupart, M. Bös, G. McKercher, L. Thauvette, G. Kukolj, P.L. Beaulieu. Discovery of a novel series of non-nucleoside thumb pocket 2 NS5B polymerase inhibitors Bioorg. Med. Chem, Lett. 2013, 23, 2585-2589 J. Park, Y.-S. Lin, Y. S. Tsantrizos, A.M. Berghuis Ternary complex structures of human farnesyl pyrophosphate synthase bound with a Novel inhibitor and secondary ligands provide insights into the molecular details of the enzyme's active site closure BMC Structural Biology 2012, 12, 32. J. W. De Schutter, Joseph Shaw, Y.-S. Lin, Y. S. Tsantrizos Design of Potent Bisphosphonate Inhibitors of the Human Farnesyl Pyrophosphate Synthase via Targeted Interactions with the Active Site "Capping" Phenyls Bioorg. Med. Chem. 2012, 20, 5583-5591 Y.-S. Lin, J. Park, J. W. De Schutter, X. F. Huang, A. M. Berghuis, M. Sebag, Y. S. Tsantrizos Design and Synthesis of Active Site Inhibitors of the Human Farnesyl Pyrophosphate Synthase - Apoptosis and Inhibition of ERK Phosphorylation in Multiple Myeloma Cells J. Med. Chem. 2012, 55, 3201-3215 P.L. Beaulieu, M. Bös, M.G. Cordingley, C. Chabot, G. Fazal, M. Garneau, J.R. Gillard, Y.S. Tsantrizos, J. Duan G. Kukolj Discovery of the first Thumb Pocket 1 NS5B polymerase inhibitor (BILB 1941) with demonstrated antiviral in patients chronically infected with genotype 1 hepatitis C virus (HCV) J. Med. Chem. 2012, 55, 7650-7666 P.L. Beaulieu, C. Chabot, J. Duan, M. Garneau, J.R. Gillard, E. Jolicoeur, M. Poirier, M.-A. Poupart, T.A. Stammers, G. Kukolj, Y.S. Tsantrizos Indole 5-carboxamide Thumb Pocket I inhibitors of HCV NS5B polymerase with nanomolar potency in cell-based subgenomic replicons (part 2): central amino acid linker and right-hand-side SAR studies Bioorg. Med. Chem. Lett. 2011, 21, 3664 Joris W. De Schutter, Serge Zaretsky, Sarah Welbourn, Arnim Pause, Youla S.Tsantrizos "Novel Bisphosponate Inhibitors of the Human Farnesyl Pyrophosphate Synthase" Bioorg. Med. Chem. Lett 2010, 20, 5781-5786 S. R. LaPlante, A. Jakalian, N. Aubry, J.R. Gillard, R. Coulombe, C. Brochu, Y. Tsantrizos, M. Poirier, G. Kukolj, P.L. Beaulieu The Importance of Ligand Bioactive Conformation in the Discovery of Potent Indole-diamide Inhibitors of the Hepatitis C Virus NS5B. J. Am. Chem. Soc. 2010, 132, 15204-15212 Y. S. Tsantrizos TMC-435, a NS3/4A Protease Inhibitor for the Treatment of HCV Infections Current Opinion in Investigational Drugs 2009, 10, 871-881. Y. S. Tsantrizos Peptidomimetic Therapeutic Agents Targeting the Protease Enzyme for the Human Immunodeficiency Virus and Hepatitis C Virus. Acc. Chem. Res. 2008, 41, 1252-1263 Y. S. Tsantrizos, J.-M. Ferland, A. McClory, M. Poirier, V. Farina, N. K. Yee, X.-J. Wang, N. Haddad, X. Wei, J. Xu, L. Zhang Olefin ring-closing metathesis as a powerful tool in drug discovery and development-potent macrocyclic inhibitors of the hepatitis C virus NS3 protease. J. Organomet. Chem. 2006, 691, 5163-5171