Department of Pharmacology


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Alex G Waterson, Ph.D.

Research Associate Professor of Pharmacology
Research Associate Professor in Chemistry
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Nashville, TN 37232-6600


postdoctoral, Colorado State University
PhD, Emory University
BS, Mississippi State University

Research Keywords

Medicinal chemistry Drug discovery

Research Description

My interests lie in the application of synthetic organic chemistry to questions of biological importance. I been engaged for the last decade in medicinal chemistry toward primarily oncology related drug discovery efforts. Previous experience with the pharmaceutical industry included a key role in the discovery of dabrafenib, currently in Phase III clinical trials for the treatment of B-Raf positive metastatic melanoma.

Currently, I lead the medicinal chemistry team of the Fesik cancer drug discovery group. We employ fragment based drug discovery techniques to discover inhibitors of "undruggable" protein-protein interactions that are important for the future discovery of cancer therapeutics. The team evaluates and optimizes hits from NMR-based fragment screens as well as HTS campaigns toward such proteins. Using concepts of structure-based drug design, we seek to grow these fragments hits and/or link them together to synthesize optimized inhibitor molecules. These molecules may become the basis for cancer drugs in the future.


Sun, Q, Burke, JP, Phan, J, Burns, MC, Olejniczak, ET, Waterson, AG, Lee, T, Rossanese, OW, Fesik, SW. Discovery of small molecules that bind to K-Ras and inhibit Sos-mediated activation. Angew Chem Int Ed Engl, 51(25), 6140-3, 2012

Delpire, E, Baranczak, A, Waterson, AG, Kim, K, Kett, N, Morrison, RD, Daniels, JS, Weaver, CD, Lindsley, CW. Further optimization of the K-Cl cotransporter KCC2 antagonist ML077: development of a highly selective and more potent in vitro probe. Bioorg Med Chem Lett, 22(14), 4532-5, 2012

Taylor, RW, Romaine, IM, Liu, C, Murthi, P, Jones, PL, Waterson, AG, Sulikowski, GA, Zwiebel, LJ. Structure-Activity Relationship of a Broad-Spectrum Insect Odorant Receptor Agonist. ACS Chem Biol, 2012

Jones, PL, Pask, GM, Romaine, IM, Taylor, RW, Reid, PR, Waterson, AG, Sulikowski, GA, Zwiebel, LJ. Allosteric antagonism of insect odorant receptor ion channels. PLoS One, 7(1), e30304, 2012

Vangamudi, B.; Ayres, A. E.; Burke, J. P.; Waterson, A. G.; Rossanese, O. W.; Fesik, S. W.. Evaluation of TBK1 as a novel cancer target in the K-Ras pathway. . Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research. , Chicago, IL, Mar 31-Apr4, 2012

Stoops, SL, Pearson, AS, Weaver, C, Waterson, AG, Days, E, Farmer, C, Brady, S, Weaver, CD, Beauchamp, RD, Lindsley, CW. Identification and optimization of small molecules that restore E-cadherin expression and reduce invasion in colorectal carcinoma cells. ACS Chem Biol, 6(5), 452-65, 2011

Stellwagen, JC, Adjabeng, GM, Arnone, MR, Dickerson, SH, Han, C, Hornberger, KR, King, AJ, Mook, RA, Petrov, KG, Rheault, TR, Rominger, CM, Rossanese, OW, Smitheman, KN, Waterson, AG, Uehling, DE. Development of potent B-RafV600E inhibitors containing an arylsulfonamide headgroup. Bioorg Med Chem Lett, 21(15), 4436-40, 2011

Thorne, CA, Hanson, AJ, Schneider, J, Tahinci, E, Orton, D, Cselenyi, CS, Jernigan, KK, Meyers, KC, Hang, BI, Waterson, AG, Kim, K, Melancon, B, Ghidu, VP, Sulikowski, GA, LaFleur, B, Salic, A, Lee, LA, Miller, DM, Lee, E. Small-molecule inhibition of Wnt signaling through activation of casein kinase 1I?. Nat Chem Biol, 6(11), 829-36, 2010

Stevens, KL, Alligood, KJ, Alberti, JG, Caferro, TR, Chamberlain, SD, Dickerson, SH, Dickson, HD, Emerson, HK, Griffin, RJ, Hubbard, RD, Keith, BR, Mullin, RJ, Petrov, KG, Gerding, RM, Reno, MJ, Rheault, TR, Rusnak, DW, Sammond, DM, Smith, SC, Uehling, DE, Waterson, AG, Wood, ER. Synthesis and stereochemical effects of pyrrolidinyl-acetylenic thieno[3,2-d]pyrimidines as EGFR and ErbB-2 inhibitors. Bioorg Med Chem Lett, 19(1), 21-6, 2009

Waterson, AG, Petrov, KG, Hornberger, KR, Hubbard, RD, Sammond, DM, Smith, SC, Dickson, HD, Caferro, TR, Hinkle, KW, Stevens, KL, Dickerson, SH, Rusnak, DW, Spehar, GM, Wood, ER, Griffin, RJ, Uehling, DE. Synthesis and evaluation of aniline headgroups for alkynyl thienopyrimidine dual EGFR/ErbB-2 kinase inhibitors. Bioorg Med Chem Lett, 19(5), 1332-6, 2009

Bhagwanth, S, Waterson, AG, Adjabeng, GM, Hornberger, KR. Room-temperature Pd-catalyzed amidation of aryl bromides using tert-butyl carbamate. J Org Chem, 74(12), 4634-7, 2009

Adjabeng, G. M.; Bifulco, N.; Davis-Ward, R. G.; Dickerson, S. H.; Hornberger, K. H.; Petrov, K.; Rheault, T. R.; Uehling, D. E.; Waterson, A. G.. Preparation of thiazole and oxazole kinase inhibitors for cancer treatment. PCT Int. Appl. , WO2009076140 A1, 2009

Laquere, S.; Arnone, M.; Moss, K.; Yang, J.; Fisher, K.; Kane-Carson, L.; Smitheman, K.; Ward, J.; Heidrich, B.; Rheault, T.; Adjebeng, G.; Hornberger, K.; Stellwagen, J.; Waterson, A.; Han, C.; Mook, Jr. R. A.; Uehling, D.; King, A. J. . A selective Raf kinase inhibitor induces cell death and tumor regression of human cancer cell lines encoding R-Raf V600E mutation. AACR-NCI-EORTC International Conference on Molecular Targets and Cancer Therapeutics, poster abstract B88, 2009

Schaaf, G. M.; Mukherjee, S.; Waterson, A. G. . Conjugate addition of sodium methanesulfinate to vinyl pyridines and diazines for the synthesis of aliphatic sulfones. Tetrahedron Lett. , 50, 1928-1933, 2009

Waterson, A. G. Delpire, E.; Days, E.; Lewis, M.; Kim, K.; Lindsley, C. W.; Weaver, C. D. . Small molecule inhibitors of the KCC2 neuronal co-transporter. Gordon Research Conference on Natural Products, poster session, 2009

Adams, J. L.; Dickerson, S. H.; Johnson, N. W.; Kuntz, K.; Petrov, K.; Ralph, J. M.; Rheault, T. R.; Schaaf, G.; Stellwagen, J.; Tian, X.; Uehling, D. E.; Waterson, A. G.; Wilson, B. Benzene sufonamide thiazole and oxazole compounds. PCT Int. Appl. (WO 2009137391 A2), 2009

Adjabeng, G. M.; Bifulco, N.; Davis-Ward, R. G.; Dickerson, S. H.; Donaldson, K. H.; Petrov, K.; Rheault, T. R.; Schaaf,. G. M.; Stellwagen, J. C.; Uehling, D. E.; Waterson, A. G.. Thiazole and oxazole kinase inhibitors. PCT Int. Appl. (WO2009032667 A1), 2009

Wood, ER, Shewchuk, LM, Ellis, B, Brignola, P, Brashear, RL, Caferro, TR, Dickerson, SH, Dickson, HD, Donaldson, KH, Gaul, M, Griffin, RJ, Hassell, AM, Keith, B, Mullin, R, Petrov, KG, Reno, MJ, Rusnak, DW, Tadepalli, SM, Ulrich, JC, Wagner, CD, Vanderwall, DE, Waterson, AG, Williams, JD, White, WL, Uehling, DE. 6-Ethynylthieno[3,2-d]- and 6-ethynylthieno[2,3-d]pyrimidin-4-anilines as tunable covalent modifiers of ErbB kinases. Proc Natl Acad Sci U S A, 105(8), 2773-8, 2008

Hubbard, RD, Dickerson, SH, Emerson, HK, Griffin, RJ, Reno, MJ, Hornberger, KR, Rusnak, DW, Wood, ER, Uehling, DE, Waterson, AG. Dual EGFR/ErbB-2 inhibitors from novel pyrrolidinyl-acetylenic thieno[3,2-d]pyrimidines. Bioorg Med Chem Lett, 18(21), 5738-40, 2008

Kuntz, K.; Uehling, D. E.; Waterson, A. G.; Emmitte, K. A.; Stevens, K.; Shotwell, J. B.; Smith, S. C.; Nailor, K. E.; Salovich, J. M.; Wilson, B. J.; Cheung, M.; Mook, R. A.; Baum, E. W.; Moorthy, G.. Imidazopyridine kinase inhibitors. U.S. Pat. Appl. Publ. (US2008300242 A1), 2008

Uehling, D. E.; Hubbard, R. D.; Waterson, A. G.; Petrov, K.; Bifulco, N. , Jr.; Wilson, J. W.; Badiang, J. G.; Cheung, M.; Yamabe, M.. Preparation of 3-(pyrimidin-4-yl)pyrazolo[1,5-a]pyridines as ErbB kinase inhibitors for treating neoplasm. PCT Int. Appl. (WO2007067506), 2007

Waterson, AG, Stevens, KL, Reno, MJ, Zhang, YM, Boros, EE, Bouvier, F, Rastagar, A, Uehling, DE, Dickerson, SH, Reep, B, McDonald, OB, Wood, ER, Rusnak, DW, Alligood, KJ, Rudolph, SK. Alkynyl pyrimidines as dual EGFR/ErbB2 kinase inhibitors. Bioorg Med Chem Lett, 16(9), 2419-22, 2006

Uehling, D. E.; Stevens, K. L.; Dickerson, S. H.; Waterson, A. G.; Harris, P. A.; Sammond, D. M.; Hubbard, R. D.; Emerson, H. K.; Wilson, J. W. . Preparation of 2-pyrimidinyl pyrazolopyridines as ErbB kinase inhibitors for treating neoplasm. PCT Int. Appl(WO2006068826), 2006

Dickerson, S. H.; Emerson, H. K.; Hinkle, K. W.; Hornberger, K. R.; Sammond, D. M.; Smith, S.; Stevens, K. L.; Hubbard, R. D.; Petrov, K. G.; Reno, M. J.; Uehling, D. E.; Waterson, A. G. . Preparation of thienopyrimidine derivatives as ErbB kinase inhibitors. PCT Int. Appl. (WO2005007083), 2005

Reno, M. J.; Stevens, K. L.; Waterson, A. G.; Zhang, Y.. Preparation of pyrimidine derivatives as ErbB kinase inhibitors. PCT Int. Appl(WO2005016914), 2005

Badiang, J. G.; Dickerson, S. H.; Donaldson, K. H.; Hinkle, K. W.; Hornberger, K. R.; Petrov, K. G.; Reno, M. J.; Stevens, K. L.; Uehling, D. E.; Waterson, A. G.. Preparation of thienopyrimidines as inhibitors of ErbB kinases. PCT Int. Appl. (WO2004112714), 2004

Padwa, A.; Waterson, A. G.. A novel synthesis of polysubstituted phenols using the SnAr reaction of 2,5-dinitrofuran.a?? . ARKIVOC, 4, 29-42, 2001

Waterson, A. G.; Meyers, A. I. . Studies directed toward the synthesis of Viridenomycin. Route 2: a second-generation approach. Tetrahedron Lett. , 42, 4305-4308, 2001

Padwa, A.; Waterson, A. G. . Synthesis of nitrogen heterocycles using the intramolecular Pummerer reaction. Curr. Org. Chem, 4, 175-203, 2000

Waterson, AG, Meyers, AI. Bicyclic lactams as chiral homoenolate equivalents: synthesis of (-)-penienone. J Org Chem, 65(21), 7240-3, 2000

Padwa, A, Waterson, AG. Studies dealing with thionium ion promoted mannich cyclization reactions. J Org Chem, 65(1), 235-44, 2000

Padwa, A.; Waterson, A. G. . The thionium/N-acyliminium ion cyclization cascade as a strategy for the synthesis of azapolycyclic ring systems . Tetrahedron(56), 10159-10173, 2000

Padwa, A.; Waterson, A.G. . Synthesis of the perhydroindolizine nucleus by a Pummerer/Mannich induced cyclization cascade. Tetrahedron Lett. , 39, 3986-3997, 1998

Padwa, A.; Dimitroff, M.; Waterson, A. G.; Wu, T. . IMDAF cycloaddition as a method for the preparation of pyrrolophenanthridine alkaloids. J. Org. Chem. , 63, 8585-8588, 1998

Padwa, A.; Dimitroff, M.; Waterson, A. G.; Wu, T. . Diels-Alder reaction of 2-amino-substituted furans as a method for preparing substituted anilines. J. Org. Chem. , 62, 4088-4096, 1997