Roush, William - The Scripps Research Institute

个人简介

Professor Roush received his bachelor's degree in chemistry, summa cum laude, from the University of California Los Angeles in 1974, where he performed undergraduate work with Scripps Research Professor Julius Rebek, Jr. He received his Ph.D. degree in chemistry from Harvard University in 1977 and after an additional year as a postdoctoral associate at Harvard, he joined the faculty of the Massachusetts Institute of Technology as an assistant professor. He moved to Indiana University in 1987 and was promoted to professor in 1989 and distinguished professor in 1995. Two years later, he went to the University of Michigan in Ann Arbor as the Warner Lambert/Parke Davis Professor of Chemistry. He served as chair of the University of Michigan's Department of Chemistry from 2002-2004. In 2004 Professor Roush relocated with his group to the Jupiter, Florida campus of the Scripps Research Institute where he currently serves as Professor of Chemistry, Associate Dean of the TSRI graduate program and Executive Director of Medicinal Chemistry.

研究领域

Over many years the major focus of our research effort has focused on the synthesis of stereochemically complex, biologically active natural products and the development of new synthetic methodology. Significant emphasis is placed on the discovery, development, and/or illustration of new reactions and synthetic methods in this research. Some of these synthesis projects have involved intramolecular cycloaddition reactions. Others make use of acyclic diastereoselective or enantioselective stereochemical techniques. We are increasingly pursuing research programs in bioorganic chemistry, chemical biology and medicinal chemistry, including the design and synthesis of inhibitors of cysteine proteases isolated from tropical parasites. Additional projects focus on the develop potent, selective inhibitors of several kinases and proteases, inhibitors of certain epigenetic targets, inhibitors (inverse agonists) or activators of nuclear receptors, the design and synthesis of selective CYP51 inhibitors, and small molecule inhibotors of carboxylic acid transporters as potential therapeutic agents, among others. Studies focusing on the development of new technology for synthesis of antibody-crug conjugates are also in progress.

近期论文

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H. Ghalei, F. X. Schaub, J. R. Doherty, Y. Noguchi, W. R. Roush, J. L. Cleveland, M. E. Stroupe, and K. Karbstein, “CK1d-directed release of Ltv1 from pre-40S ribosomes is necessary for risobome assembly and cellular growth,” Molecular Cell 2014, in press. Y. Wang, R. L. Stowe, C. E. Pinello, G. Tian, F. Madoux, D. Li, L. Y. Zhao, J.-L. Li, K. R. Geary, H. Ma, P. Hodder, W. R. Roush, and D. Liao, “Identification of novel small-molecule HDAC inhibitors that selectively inhibit class I HDACs and kill cancer cells through HDAC inhibition,” Chemistry & Biology, 2014, in press. C. Corzo, Y. Mari, M. R. Chang, D. Kuruvilla, P. Nuhant, N. Kumar, G. M. West, D. Duckett, W. R. Roush, and P. R. Griffin, “Anti-proliferation activity of a small molecule repressor of LRH1,” Mol. Pharmacol. 2014, in press. D. F. Vieira, J. Y. Choi, C. M. Calvet, J. L. Siqueira-Neto, J. B. Johnston, D. Kellar, J. Gut, M. D. Cameron, J. H. McKerrow, W. R. Roush and L. M. Podust, “Binding mode and potency of N-indolyl-oxopyridinyl-4-aminopropanyl-based inhibitors targeting Trypanosoma cruzi CYP51,” J. Med. Chem. 2014, 57,10162. 10.1021/jm501568b T. P. Spicer, J. Jiang, A. B. Taylor, P. J. Hart, W. R. Roush, G. B. Fields, Peter S. Hodder, and D. Minond, “Characterization of Selective Exosite-Binding Inhibitors of Matrix Metalloproteinase 13 That Prevent Articular Cartilage Degradation In Vitro”, J. Med. Chem. 2014, 57, 9598. 10.1021/jm501284e C. Penas, J. K. Mishra, S. D. Wood, S. C. Schurer, W. R. Roush and N. G. Ayad, “GSK3 Inhibitors Stabilize Wee1 and Reduce Cerebellar Granule Cell Progenitor Proliferation,” Cell Cycle, 2015, 14, 417. 10.4161/15384101.2014.974439 J. Y. Choi, L. Podust, and W. R. Roush, “Drug Strategies Targeting CYP51 in Neglected Tropical Diseases,” Chem. Rev. 2014, 114, 11242. 10.1021/cr5003134 C.M Calvet, D.F. Vieira, J.Y. Choi, D. Kellar, M.D. Cameron, J.L. Siqueira-Neto, J. Gut, J.B. Johnson, L. Lin, S. Khan, J.H. McKerrow, W.R. Roush, L.M. Podust, "4-Aminopyridyl-Based CYP51 Inhibitors as Anti-Trypanosoma cruzi Drug Leads with Improved Pharmacokinetic Profile and in Vivo Potency," J. Med. Chem. 2014, 6989-7005. 10.1021/jm500448u H. Wang, C. Yang, J. R. Doherty, W. R. Roush, J. L. Cleveland, T. D. Bannister, “Synthesis and Structure Activity Relationships of Pteridine Dione and Trione Monocarboxylate Transporter 1 Inhibitors,” J. Med. Chem. 2014, 57, 7317. 10.1021/jm500640x C. Penas, V. Ramachandran, S. Simanski, C. Lee, F. Madoux, R. J. Rahaim, R. Chauhan, O. Barnaby, S. Schurer, P. Hodder, J. Steen, W. R. Roush, and N. G. Ayad, “Casein Kinase 1d Dependent Wee1 Degradation,” J. Biol. Chem. 2014, 289, 18893. 10.1074/jbc.M114.547661 D. F. Vieira, J. Y. Choi, W. R. Roush,] and L. M. Podust, "Expanding the Binding Envelope of CYP51 Inhibitors Targeting Trypanosoma cruzi with 4-Aminopyridyl-Based Sulfonamide Derivatives," ChemBioChem, 2014, 1111. 10.1002/cbic.201402027 J. Y. Choi, C. M. Calvet, D. F. Vieira, S. S. Gunatilleke, M. D. Cameron, J. H. McKerrow, L. M. Podust, and W. R. Roush, "R-Configuration of 4-Aminopyridyl-Based Inhibitors of CYP51 Confers Superior Efficacy Against Trypanosoma cruzi," Med. Chem. Lett. 2014, 434. 10.1021/ml500010m J. R. Doherty, C. Yang, K. E. N. Scott, M. D. Cameron, M. Fallahi, W. Li, M. A. Hall, A. L. Amelio, J. K. Mishra, F. Li, M. Tortosa, H. M. Genau, R. J. Rounbehler, Y. Lu, C. V. Dang, K. G. Kumar, A. A. Butler, T. D. Bannister, A. Hooper, K. Unsal-Kacmaz, W. R. Roush and J. L. Cleveland, “Blocking lactate export by inhibiting the Myc target Mct1 Disables Glycolysis and Glutathione Metabolism,” Cancer Res. 2014, 74, 908-920. 10.1158/0008-5472.CAN-13-2034 J. Kister, D. S. Ess, and W. R. Roush, "Enantio- and Diastereoselective Synthesis of syn-β-Hydroxy-α-Vinyl Carboxylic Esters via Reductive Aldol Reactions of Ethyl Allenecarboxylate with 10-TMS-9-Borabicyclo[3.3.2]decane and DFT Analysis of the Hydroboration Pathway,"Org. Lett. 2013, 15, 5436. 10.1021/ol4025277 C. Allais, A. S. Tsai, P. Nuhant, and W. R. Roush, "Highly Diastereo- and Enantioselective Aldol Reactions of Stereodefined Tetrasubstituted Enolborinates Generated By 1,4- Hydroboration of α,β-Unsaturated Morpholine Carboxamides with (Diisopinocampheyl)borane," Angew. Chem. Int. Ed. 2013, 52, 12888–12891. 10.1002/anie.201307302 J. Y. Choi, C. M. Calvet, S. S. Gunatilleke, C. Ruiz, M. D. Cameron, J. H. McKerrow, L. M. Podust, and W. R. Roush, "Rational development of 4-aminopyridyl-based inhibitors targeting 22 Trypanosoma cruzi CYP51 as anti-Chagas agents," J. Med. Chem., 2013, 56, 7651. 10.1021/jm401067s C. Allais, P. Nuhant, and W. R. Roush, "(Diisopinocampheyl)borane-Mediated ReductiveAldol Reactions of Acrylate Esters: Enantioselective Synthesis of Anti-Aldols," Org. Lett. 2013, 15, 3922. 10.1021/ol401679g M. Chen and W. R. Roush, "Enantioselective Synthesis of (Z)-2-Methyl-1,5-anti- and (E)-2- Methyl-1,5-anti-Pentenediols Via an Allene Hydroboration-Double Allylboration Reaction Sequence," J. Am. Chem. Soc. 2013, 135, 9512. 10.1021/ja4033633 P. Nuhant, C. Allais and W. R. Roush, "(Diisopinocampheyl)borane-Mediated Reductive Aldol Reactions: Highly Enantio- and Diastereoselective Synthesis of Syn-Aldols from NAcryloylmorpholine," Angew. Chem. Int. Ed. 2013, 52, 8703. 10.1002/anie.201302535 M. Bibian, R. J. Rahaim, J. Y. Choi, Y. Noguchi, S. Schürer, W. Chen, S. Nakanishi, K. Licht, L. H. Rosenberg, L. Li, Y. Feng, M. D. Cameron, D. R. Duckett, J. L. Cleveland and W. R. Roush, "Development of Highly Selective Casein Kinase 1δ/1ε (CK1δ/ε) Inhibitors with Potent Antiproliferatve Properties," Bioorg. Med. Chem. Lett. 2013, 23, 4374. 10.1016/j.bmcl.2013.05.075