The focus of our lab is on cancer drug discovery using fragment-based approaches and structure-based design. To accomplish this goal, we have assembled a multidisciplinary team that includes structural biologists, medicinal chemists, and cell biologists. Among them are five research professors and several research assistants, postdoctoral fellows, and graduate students. In our lab, we clone, express, and purify proteins, conduct fragment-based screens, determine the three-dimensional structures of protein/ligand complexes using NMR and/or X-ray crystallography, design and synthesize compounds, and test compounds in primary and secondary biological assays. The cancer drug targets that we are pursuing are highly validated but technically challenging such as K-Ras and c-Myc.


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

Featured publications are shown below:

  1. Drugging the undruggable RAS: Mission possible? Cox AD, Fesik SW, Kimmelman AC, Luo J, Der CJ (2014) Nat Rev Drug Discov 13(11): 828-51
    › Primary publication · 25323927 (PubMed) · PMC4355017 (PubMed Central)
  2. Fragment-based screening of the bromodomain of ATAD2. Harner MJ, Chauder BA, Phan J, Fesik SW (2014) J Med Chem 57(22): 9687-92
    › Primary publication · 25314628 (PubMed) · PMC4255743 (PubMed Central)
  3. Small molecule Mcl-1 inhibitors for the treatment of cancer. Belmar J, Fesik SW (2015) Pharmacol Ther : 76-84
    › Primary publication · 25172548 (PubMed) · PMC4340597 (PubMed Central)
  4. A method for the second-site screening of K-Ras in the presence of a covalently attached first-site ligand. Sun Q, Phan J, Friberg AR, Camper DV, Olejniczak ET, Fesik SW (2014) J Biomol NMR 60(1): 11-4
    › Primary publication · 25087006 (PubMed) · PMC4358732 (PubMed Central)
  5. 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)
  6. 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)
  7. 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)
  8. 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)
  9. 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)
  10. Fragment-based drug discovery using NMR spectroscopy. Harner MJ, Frank AO, Fesik SW (2013) J Biomol NMR 56(2): 65-75
    › Primary publication · 23686385 (PubMed) · PMC3699969 (PubMed Central)
  11. Discovery of potent myeloid cell leukemia 1 (Mcl-1) inhibitors using fragment-based methods and structure-based design. Friberg A, Vigil D, Zhao B, Daniels RN, Burke JP, Garcia-Barrantes PM, Camper D, Chauder BA, Lee T, Olejniczak ET, Fesik SW (2013) J Med Chem 56(1): 15-30
    › Primary publication · 23244564 (PubMed) · PMC3646517 (PubMed Central)
  12. 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)
  13. A high-throughput fluorescence polarization anisotropy assay for the 70N domain of replication protein A. Souza-Fagundes EM, Frank AO, Feldkamp MD, Dorset DC, Chazin WJ, Rossanese OW, Olejniczak ET, Fesik SW (2012) Anal Biochem 421(2): 742-9
    › Primary publication · 22197419 (PubMed) · PMC3274598 (PubMed Central)