R. Kiplin Guy, PhD
R. Kiplin Guy, PhD

R. Kiplin Guy, PhD

Member, St. Jude Faculty

  • Chair, Chemical Biology & Therapeutics Department



PhD – The Scripps Research Institute, La Jolla, California (1996)

Research Interests

  • Orphan Diseases: malaria, sleeping sickness, retinoblastoma, ependymoma
  • Medicinal chemistry: parallel chemistry, peptidomimetics, hormone antagonists, protease inhibitors
  • Cellular biology: chemical target validation, lipid homeostasis, nuclear hormone receptors, protein interactions
  • High throughput screening: quantitative assays, data analysis methods

Selected Publications

Zhang Y, Clark JA, Connelly MC, Zhu F, Min J, Guiguemde WA, Pradhan A, Iyer L, Furimsky A, Gow J, Parman T, El Mazouni F, Phillips MA, Kyle DE, Mirsalis J, Guy RK. Lead optimization of 3-carboxyl-4(1H)-quinolones to deliver orally bioavailable antimalarials. J Med Chem 55(9): 4205-4219, 2012.

Lowes DJ, Guiguemde WA, Connelly MC, Zhu F, Sigal MS, Clark JA, Lemoff AS, Derisi JL, Wilson EB, Guy RK. Optimization of propafenone analogues as antimalarial leads. J Med Chem 54(21):7477-85, 2011.

Zhang F, Tagen M, Throm S, Mallari J, Miller L, Guy RK, Dyer MA, Williams RT, Roussel MF, Nemeth K, Zhu F, Zhang J, Lu M, Panetta JC, Boulos N, Stewart CF. Whole-body physiologically based pharmacokinetic model for nutlin-3a in mice after intravenous and oral administration Drug Metab Dispos 39(1):15-21, 2011.

Guiguemde WA, Shelat AA, Bouck D, Duffy S, Crowther GJ, Davis PH, Smithson DC, Connelly M, Clark J, Zhu F, Jimenez-Diaz MB, Martinez MS, Wilson EB, Tripathi AK, Gut J, Sharlow ER, Bathurst I, El Mazouni F, Fowble JW, Forquer I, McGinley PL, Castro S, Angulo-Barturen I, Ferrer S, Rosenthal PJ, Derisi JL, Sullivan DJ, Lazo JS, Roos DS, Riscoe MK, Phillips MA, Rathod PK, Van Voorhis WC, Avery VM, Guy RK. Chemical genetics of Plasmodium falciparum Nature 465(7296):311-315, 2010.

Reed D, Ying S, Shelat A, Mills N, Smithson D, Arnold A, Otieno S, Regni C, Zhu F, Kriwacki R, Schulman B, Guy RK, Dyer MA. "Identification and characterization of a small molecule inhibitor of MDMX," J Biol Chem 285(14):10786-10796, 2010.

Jones JO, Bolton EC, Huang Y, Feau C, Guy RK, Yamamoto KR, Hann B, Diamond MI. "Ligand independent androgen receptor inhibition in vitro and in vivo," Proc Natl Acad Sci USA. 106(17):7233-7238, 2009. PMCID: PMC2678452.  

Mallari, J. P.; Shelat, A. A.; O'Brien, T.; Caffrey, C. R.' Kosinski, A.; Connelly, M.; McKerrow, J. H.; Guy, R. K. "Development of Potent Purine-Derived Nitrile Inhibitors of the Trypanosomal Protease TbCatB," J. Med. Chem. 51(3): 545-552, 2008.  

Jouravel, N.; Sablin, E.; Arnold, L. A.; Guy, R. K.; Fletterick, R. J. "Interaction between the Androgen Receptor and a Segment of its Corepressor SHP," Acta Cryst. D63: 1198-1200, 2007.

Estebanez-Perpina, E.; Jouravel, N.; Arnold, A.; Togashi, M.; Blethrow, J.; Mar, E.; Nguyen, P.; Baxter, J. D.; Webb, P.; Guy, R. K.; Fletterick, R. J. "Structural Insight into the Mode of Action of a Direct Inhibitor of Thyroid Hormone Receptor Coregulator Binding," Mol. Endocrin. 21(12): 2919-2928, 2007.  

Estebanez-Perpina, E.; Arnold, A. Webb, P.; Nguyen, P.; Delgado-Rodrigues, E.; Mar, E.; Bateman, R.; Pallai, P.; Shokat, K. M.; Baxter, J. D.; Guy, R. K.; Fletterick, R. J.; "A surface on the androgen receptor that allosterically regulates coactivator binding.," Proc. Natl. Acad. Sci. USA 104(41): 16074-16079, 2007.  

Hyatt, J. L.; Wadkins, R. M.; Tsurkan, L.; Hicks, L. D.; Hatfield, M. J.; Edwards, C. C.; Ross, C. R.; Cantalupo, S. A.; Crundwell, G.; Guy, R. K.; Potter, P. M. "Planarity and Constraint of the Carbonyl Groups in 1,2-diones are Determinants for Selective Inhibition of Human Carboxylesterase 1," J. Med. Chem. 50(23): 5727-5734, 2007.  

Guy, R. K. "Cures for Neglected Diseases: Alternative Strategies for Finding Drugs," Curr. Op. Chem. Biol. 11(4): 10-11, 2007.

Arnold, A.; Kosinski, A.; Estebanez-Perpina, E; Fletterick, R. J.; Guy, R. K.; "Inhibitors of the Interaction of Thyroid Hormone Receptor and Coactivators: Preliminary Structure Activity Relationships," J. Med. Chem. 50(22): 5269-5280, 2007.  

Mills, N. L.; Shelat, A. A.; Guy, R. K. "Assay Optimization and Screening of RNA:Protein Interactions by Alphascreen," J. Biomol. Screen. 12(7): 946-955, 2007.  

Shelat, A.; Guy, R. K. "The Role of Scaffolds in Defining Functional Diversity of Screening Collections in Biologically Relevant Space," Nat. Chem. Biol. 3(8): 442-446, 2007.  

Shelat, A.; Guy, R. K. "The Interdependence between Screening Methods and Screening Libraries," Curr. Op. Chem. Biol. 11(3): 244-251, 2007.

Inglese, J.; Shamu, C. E.; Guy, R. K. "Reporting Data from High Throughput Screening of Small Molecule Libraries," Nat. Chem. Biol. 3(8): 438-441, 2007.

Warhust, D. C.; Craig, J. C.; Adagu, I. S.; Guy, R. K.; Madrid, P. B.; Fivelman, Q. L. "Activity of Piperaquine and other 4-aminoquinoline Antiplasmodial Drugs against Chloroquine-sensitive and Resistant Blood-stages of Plasmodium Falciparum. Role of beta-haematin inhibition and drug concentration in vacuolar water- and liquid-phases," Biochem. Pharmacol. 73(12): 1910-1926, 2007.

Fujii, N.; You, L.; Xu, Z.; Uematsu, K.; Shan, J.; He, B.; Mikami, I.; Edmondson, L. R.; Neale, G.; Zheng, J.;  Guy, R. K.; Jablons, D. M. "An Antagonist of Dishevelled Protein-Protein Interaction Suppresses b-catenin Dependent Tumor Cell Growth," Cancer Research 67(2): 573-579, 2007.  

Laurie, N. A.; Donovan, S. L.; Shih, C.-S.; Zhang, J.; Mills, N.; Fuller, C.; Teunisse, A.; Lam, S.; Ramos, Y.; Mohan, A.; Johnson, D.; Wilson, M.; Rodriguez-Galindo, C.; Quarto, M.; Francoz, S.; Mendrysa, S. M.; Guy, R. K.; Marine, J.-C.; Jochemsen, A. G.; Dyer, M. A. "Inactivation of the p53 Pathway in Retinoblastoma," Nature, 444(7115): 66-69, 2006.  

Fujii, N.; Shelat, A.; Hall, R. A.; Guy, R. K. "Design of a Selective Chemical Probe for Class I PDZ Domains," Bioorg. Med. Chem. Lett. 17(2): 546-548, 2006.  

Fujii, N.; Haresco, J. J.; Novak, K. A. P.; Gage, R. M.; Pedemonte, N.; Stokoe, D., Kuntz; I. D.; Guy, R. K. "Rational Design of a Nonpeptide General Chemical Scaffold for Reversible Inhibition of PDZ Domain Interactions," Bioorg. Med. Chem. Lett. 17(2): 549-552, 2006.  

Anderson, M. O.; Yu, H.; Penaranda, C.; Maddux, B. A.; Goldfine, I. D.; Youngren, J. F.; Guy, R. K. "Parallel Synthesis of Diarylureas and their Evaluation as Inhibitors of Insulin-Like Growth Factor Receptor," J. Comb. Chem. 8(5): 784-90, 2006.  

Mayer, M.; Lang, P. T.; Gerber, S.; Madrid, P. B.; Gomez-Pinto, I.; Guy, R. K.; James, T. L. “Synthesis and Testing of a Focused Phenothiazine Library for Binding to HIV-1 TAR RNA,” Chem. Biol. 13(9): 993-1000, 2006.  

Arnold, A.; Guy, R. K. "Synthesis of highly substituted dibenzo[b,f]azocines and their evaluation as protein kinase inhibitors," Bioorg. Med. Chem. Lett. in press, 2006.  

Weisman, J. L.; Liou, A. P., Shelat, A. A.; Cohen, F. E.; Guy, R. K; DeRisi, J. L. "Searching for New Antimalarial Therapeutics amongst Known Drugs," Chem. Biol. Drug. Des. 67(5): 409-416, 2006.

Last update: June 2012