Professor of Chemistry, Executive Director of Medicinal Chemistry, and Associate Dean, Kellogg School of Science and Technology The Scripps Research Institute
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William R. Roush joined the faculty of the Scripps Research Institute, Florida, in 2005 as Professor of Chemistry, Executive Director of Medicinal Chemistry, and Associate Dean of the Kellogg School of Science and Technology. He previously held faculty positions at the Massachusetts Institute of Technology (1978-86), Indiana University (1987-1996) and the University of Michigan (1996-2004), and was Chairman of the Department of Chemistry, University of Michigan, from 2002-2004. He is well known for research in organic synthetic methodology, natural products synthesis, and medicinal chemistry. He has had a long-term collaboration with Dr. James McKerrow of UCSF on the design and synthesis of inhibitors of cysteine proteases targeting parasitic diseases including Trypanosoma cruzi. More recently, he has collaborated with Dr. Larissa Podust of UCSF on the design and synthesis of inhibitors of Cyp51, a newly validated target for treatment of T. cruzi infections. He also has an ongoing collaboration with Dr. Sharon Reed of UCSD and Dr. McKerrow on the development of a treatment of Entamoeba histolytica infections based on the novel cysteine protease inhibitor, WRR-483, that was developed in his laboratory. Significantly, WRR-483 has also provided an experimental cure for T. cruzi infections in mice. In the past several years at Scripps Florida, he has initiated new research projects involving the development of small molecule modulators of nuclear receptors as well as inhibitors of kinases, protein arginine methyl transferases and carboxylate transporters, among others.
Synthesis and Evaluation of Oxyguanidine Analogues of the Cysteine Protease Inhibitor WRR-483 against Cruzain. ACS Med Chem Lett. 2016 Jan 14;7(1):77-82. doi: 10.1021/acsmedchemlett.5b00336. Jones BD, Tochowicz A, Tang Y, Cameron MD, McCall LI, Hirata K, Siqueira-Neto JL, Reed SL, McKerrow JH, Roush WR.
Targeting Ergosterol biosynthesis in Leishmania donovani: essentiality of sterol 14 alpha-demethylase. PLoS Negl Trop Dis. 2015 Mar;9(3):e0003588. doi: 10.1371/journal.pntd.0003588. McCall LI, El Aroussi A, Choi JY, Vieira DF, De Muylder G, Johnston JB, Chen S, Kellar D, Siqueira-Neto JL, Roush WR, Podust LM, McKerrow JH.
Binding mode and potency of N-indolyloxopyridinyl-4-aminopropanyl-based inhibitors targeting Trypanosoma cruzi CYP51. J Med Chem. 2014 Dec 11;57(23):10162-75. doi: 10.1021/jm501568b. Epub 2014 Nov 25. Vieira DF, Choi JY, Calvet CM, Siqueira-Neto JL, Johnston JB, Kellar D, Gut J, Cameron MD, McKerrow JH, Roush WR, Podust LM.
Drug strategies targeting CYP51 in neglected tropical diseases. Chem Rev. 2014 Oct 22. [Epub ahead of print] No abstract available. Choi JY, Podust LM, Roush WR.
4-Aminopyridyl-based CYP51 inhibitors as anti-Trypanosoma cruzi drug leads with improved pharmacokinetic profile and in vivo potency. J Med Chem. 2014 Aug 28;57(16):6989-7005. doi: 10.1021/jm500448u. Epub 2014 Aug 19. Calvet CM, Vieira DF, Choi JY, Kellar D, Cameron MD, Siqueira-Neto JL, Gut J, Johnston JB, Lin L, Khan S, McKerrow JH, Roush WR, Podust LM.
R-Configuration of 4-aminopyridyl-based inhibitors of CYP51 confers superior efficacy against Trypanosoma cruzi. ACS Med Chem Lett. 2014 Apr 10;5(4):434-9. doi: 10.1021/ml500010m. Choi JY, Calvet CM, Vieira DF, Gunatilleke SS, Cameron MD, McKerrow JH, Podust LM, Roush WR.
Expanding the binding envelope of CYP51 inhibitors targeting Trypanosoma cruzi with 4-aminopyridyl-based sulfonamide derivatives. Chembiochem. 2014 May 26;15(8):1111-20. doi: 10.1002/cbic.201402027. Epub 2014 Apr 25. Vieira DF, Choi JY, Roush WR, Podust LM.
Rational development of 4-aminopyridyl-based inhibitors targeting Trypanosoma cruzi CYP51 as anti-chagas agents. J Med Chem. 2013 Oct 10;56(19):7651-68. doi: 10.1021/jm401067s. Epub 2013 Sep 30. Choi JY, Calvet CM, Gunatilleke SS, Ruiz C, Cameron MD, McKerrow JH, Podust LM, Roush WR.
In vitro and in vivo studies of the trypanocidal properties of WRR-483 against Trypanosoma cruzi. PLoS Negl Trop Dis. 2010 Sep 14;4(9). doi:pii: e825. 10.1371/journal.pntd.0000825. Chen YT, Brinen LS, Kerr ID, Hansell E, Doyle PS, McKerrow JH, Roush WR.
A novel Entamoeba histolytica cysteine proteinase, EhCP4, is key for invasive amebiasis and a therapeutic target. J Biol Chem. 2010 Jun 11;285(24):18516-27. doi: 10.1074/jbc.M109.086181. Epub 2010 Apr 8. He C, Nora GP, Schneider EL, Kerr ID, Hansell E, Hirata K, Gonzalez D, Sajid M, Boyd SE, Hruz P, Cobo ER, Le C, Liu WT, Eckmann L, Dorrestein PC, Houpt ER, Brinen LS, Craik CS, Roush WR, McKerrow J, Reed SL.
Synthesis of macrocyclic trypanosomal cysteine protease inhibitors. Bioorg Med Chem Lett. 2008 Nov 15;18(22):5860-3. doi: 10.1016/j.bmcl.2008.06.012. Epub 2008 Jun 10. Chen YT, Lira R, Hansell E, McKerrow JH, Roush WR.
Use of recombinant Entamoeba histolytica cysteine proteinase 1 to identify a potent inhibitor of amebic invasion in a human colonic model. Eukaryot Cell. 2007 Jul;6(7):1130-6. Epub 2007 May 18. Meléndez-López SG, Herdman S, Hirata K, Choi MH, Choe Y, Craik C, Caffrey CR, Hansell E, Chávez-Munguía B, Chen YT, Roush WR, McKerrow J, Eckmann L, Guo J, Stanley SL Jr, Reed SL.
Active site mapping, biochemical properties and subcellular localization of rhodesain, the major cysteine protease of Trypanosoma brucei rhodesiense. Mol Biochem Parasitol. 2001 Nov;118(1):61-73. Caffrey CR, Hansell E, Lucas KD, Brinen LS, Alvarez Hernandez A, Cheng J, Gwaltney SL 2nd, Roush WR, Stierhof YD, Bogyo M, Steverding D, McKerrow JH.
Potent second generation vinyl sulfonamide inhibitors of the trypanosomal cysteine protease cruzain. Bioorg Med Chem Lett. 2001 Oct 22;11(20):2759-62. Roush WR, Cheng J, Knapp-Reed B, Alvarez-Hernandez A, McKerrow JH, Hansell E, Engel JC.
A target within the target: probing cruzain's P1' site to define structural determinants for the Chagas' disease protease. Structure. 2000 Aug 15;8(8):831-40. Brinen LS, Hansell E, Cheng J, Roush WR, McKerrow JH, Fletterick RJ.
Structure-based design, synthesis and evaluation of conformationally constrained cysteine protease inhibitors. Bioorg Med Chem. 1998 Dec;6(12):2477-94. Scheidt KA, Roush WR, McKerrow JH, Selzer PM, Hansell E, Rosenthal PJ.
Design and synthesis of dipeptidyl alpha',beta'-epoxy ketones, potent irreversible inhibitors of the cysteine protease cruzain. Bioorg Med Chem Lett. 1998 Oct 6;8(19):2809-12. Roush WR, González FV, McKerrow JH, Hansell E.