Alex Waterson
Faculty Member
Last active: 3/21/2014


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.


The following timeline graph is generated from all co-authored publications.

Featured publications are shown below:

  1. Approach for targeting Ras with small molecules that activate SOS-mediated nucleotide exchange. Burns MC, Sun Q, Daniels RN, Camper D, Kennedy JP, Phan J, Olejniczak ET, Lee T, Waterson AG, Rossanese OW, Fesik SW (2014) Proc Natl Acad Sci U S A 111(9): 3401-6
    › Primary publication · 24550516 (PubMed) · PMC3948241 (PubMed Central)
  2. Discovery of a potent stapled helix peptide that binds to the 70N domain of replication protein A. Frank AO, Vangamudi B, Feldkamp MD, Souza-Fagundes EM, Luzwick JW, Cortez D, Olejniczak ET, Waterson AG, Rossanese OW, Chazin WJ, Fesik SW (2014) J Med Chem 57(6): 2455-61
    › Primary publication · 24491171 (PubMed) · PMC3969094 (PubMed Central)
  3. Discovery of a potent inhibitor of replication protein a protein-protein interactions using a fragment-linking approach. Frank AO, Feldkamp MD, Kennedy JP, Waterson AG, Pelz NF, Patrone JD, Vangamudi B, Camper DV, Rossanese OW, Chazin WJ, Fesik SW (2013) J Med Chem 56(22): 9242-50
    › Primary publication · 24147804 (PubMed) · PMC3932990 (PubMed Central)
  4. Surface reengineering of RPA70N enables cocrystallization with an inhibitor of the replication protein A interaction motif of ATR interacting protein. Feldkamp MD, Frank AO, Kennedy JP, Patrone JD, Vangamudi B, Waterson AG, Fesik SW, Chazin WJ (2013) Biochemistry 52(37): 6515-24
    › Primary publication · 23962067 (PubMed) · PMC3804075 (PubMed Central)
  5. Discovery of Protein-Protein Interaction Inhibitors of Replication Protein A. Patrone JD, Kennedy JP, Frank AO, Feldkamp MD, Vangamudi B, Pelz NF, Rossanese OW, Waterson AG, Chazin WJ, Fesik SW (2013) ACS Med Chem Lett 4(7): 601-605
    › Primary publication · 23914285 (PubMed) · PMC3728914 (PubMed Central)
  6. Structure-activity relationship of a broad-spectrum insect odorant receptor agonist. Taylor RW, Romaine IM, Liu C, Murthi P, Jones PL, Waterson AG, Sulikowski GA, Zwiebel LJ (2012) ACS Chem Biol 7(10): 1647-52
    › Primary publication · 22924767 (PubMed)
  7. Further optimization of the K-Cl cotransporter KCC2 antagonist ML077: development of a highly selective and more potent in vitro probe. Delpire E, Baranczak A, Waterson AG, Kim K, Kett N, Morrison RD, Daniels JS, Weaver CD, Lindsley CW (2012) Bioorg Med Chem Lett 22(14): 4532-5
    › Primary publication · 22727639 (PubMed) · PMC3389279 (PubMed Central)
  8. Discovery of small molecules that bind to K-Ras and inhibit Sos-mediated activation. Sun Q, Burke JP, Phan J, Burns MC, Olejniczak ET, Waterson AG, Lee T, Rossanese OW, Fesik SW (2012) Angew Chem Int Ed Engl 51(25): 6140-3
    › Primary publication · 22566140 (PubMed) · PMC3620661 (PubMed Central)
  9. Allosteric antagonism of insect odorant receptor ion channels. Jones PL, Pask GM, Romaine IM, Taylor RW, Reid PR, Waterson AG, Sulikowski GA, Zwiebel LJ (2012) PLoS One 7(1): e30304
    › Primary publication · 22272331 (PubMed) · PMC3260273 (PubMed Central)
  10. Development of potent B-RafV600E inhibitors containing an arylsulfonamide headgroup. 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 (2011) Bioorg Med Chem Lett 21(15): 4436-40
    › Primary publication · 21733693 (PubMed)
  11. Identification and optimization of small molecules that restore E-cadherin expression and reduce invasion in colorectal carcinoma cells. Stoops SL, Pearson AS, Weaver C, Waterson AG, Days E, Farmer C, Brady S, Weaver CD, Beauchamp RD, Lindsley CW (2011) ACS Chem Biol 6(5): 452-65
    › Primary publication · 21241068 (PubMed) · PMC3401128 (PubMed Central)
  12. Small-molecule inhibition of Wnt signaling through activation of casein kinase 1α. 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 (2010) Nat Chem Biol 6(11): 829-36
    › Primary publication · 20890287 (PubMed) · PMC3681608 (PubMed Central)
  13. Room-temperature Pd-catalyzed amidation of aryl bromides using tert-butyl carbamate. Bhagwanth S, Waterson AG, Adjabeng GM, Hornberger KR (2009) J Org Chem 74(12): 4634-7
    › Primary publication · 19518153 (PubMed)
  14. Synthesis and evaluation of aniline headgroups for alkynyl thienopyrimidine dual EGFR/ErbB-2 kinase inhibitors. 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 (2009) Bioorg Med Chem Lett 19(5): 1332-6
    › Primary publication · 19208477 (PubMed)
  15. Synthesis and stereochemical effects of pyrrolidinyl-acetylenic thieno[3,2-d]pyrimidines as EGFR and ErbB-2 inhibitors. 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 (2009) Bioorg Med Chem Lett 19(1): 21-6
    › Primary publication · 19028424 (PubMed)
  16. Dual EGFR/ErbB-2 inhibitors from novel pyrrolidinyl-acetylenic thieno[3,2-d]pyrimidines. Hubbard RD, Dickerson SH, Emerson HK, Griffin RJ, Reno MJ, Hornberger KR, Rusnak DW, Wood ER, Uehling DE, Waterson AG (2008) Bioorg Med Chem Lett 18(21): 5738-40
    › Primary publication · 18842405 (PubMed)
  17. 6-Ethynylthieno[3,2-d]- and 6-ethynylthieno[2,3-d]pyrimidin-4-anilines as tunable covalent modifiers of ErbB kinases. 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 (2008) Proc Natl Acad Sci U S A 105(8): 2773-8
    › Primary publication · 18287036 (PubMed) · PMC2268535 (PubMed Central)
  18. Alkynyl pyrimidines as dual EGFR/ErbB2 kinase inhibitors. 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 (2006) Bioorg Med Chem Lett 16(9): 2419-22
    › Primary publication · 16483772 (PubMed)
  19. Bicyclic lactams as chiral homoenolate equivalents: synthesis of (-)-penienone. Waterson AG, Meyers AI (2000) J Org Chem 65(21): 7240-3
    › Primary publication · 11031061 (PubMed)
  20. Studies dealing with thionium ion promoted mannich cyclization reactions. Padwa A, Waterson AG (2000) J Org Chem 65(1): 235-44
    › Primary publication · 10813921 (PubMed)