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Fesik Lab

Publications

  1. Fesik, S.W. Isotope-edited NMR spectroscopy.  Nature. 332, 865-866 (1988).
  2. Fesik, S.W. and E.R.P. Zuiderweg. Heteronuclear three-dimensional NMR spectroscopy.  A strategy for the simplification of homonuclear two-dimensional NMR spectra.  J. Magn. Reson. 78, 588-593 (1988).
  3. Fesik, S.W., H.L. Eaton, E.T. Olejniczak, E.R.P. Zuiderweg, L.P. McIntosh, and F.W. Dahlquist. 2D and 3D NMR Spectroscopy employing 13C-13C magnetization transfer by isotropic mixing.  Spin system identification in large proteins.  J. Am. Chem. Soc. 112, 886-888 (1990).
  4. Fesik, S.W., R.T. Gampe, Jr., T.F. Holzman, D.A. Egan, R. Edalji, J.R. Luly, R. Simmer, and R. Helfrich. Isotope-edited NMR of cyclosporin A bound to cyclophilin: Evidence for a trans 9,10 amide bond. Science. 250, 1406-1409 (1990).
  5. Theriault, Y., T.M. Logan, R. Meadows, L. Yu, E. T. Olejniczak, T.F. Holzman, R.L. Simmer, and S.W. Fesik. Solution structure of the cyclosporin A/cyclophilin complex by NMR.  Nature. 361, 88-91 (1993).
  6. Yoon, H.S., P.J. Hajduk, A.M. Petros, E.T. Olejniczak, R.P. Meadows, and S.W. Fesik. Solution structure of a pleckstrin homology domain. Nature. 369, 672-675 (1994).
  7. Harlan, J.E., P.J. Hajduk, H.S. Yoon, and S.W. Fesik. Pleckstrin homology domains bind to phosphatidylinositol 4,5-bisphosphate. Nature. 371, 167-170 (1994).
  8. Zhou, M.-M., K.S. Ravichandran, E.T. Olejniczak, A.M. Petros, R.P. Meadows, M. Sattler, J.E. Harlan, W.S. Wade, S.J. Burakoff, and S.W. Fesik. Structure and ligand recognition of the phosphotyrosine binding domain of Shc.  Nature. 378, 584-592 (1995).
  9. Muchmore, S.W., M. Sattler, H. Liang, R.P. Meadows, J.E. Harlan, H.S. Yoon, D. Nettesheim, B.S. Chang, C.B. Thompson, S.-L. Wang, S.-C. Ng, and S.W. Fesik. X-ray and NMR structure of human Bcl-XL, an inhibitor of programmed cell death.  Nature. 381, 335-341 (1996).
  10. Shuker, S.B., P.J. Hajduk, R.P. Meadows, and S.W. Fesik.  Discovering high-affinity ligands for proteins:  SAR by NMR.  Science. 274, 1531-1534 (1996).
  11. Huang, B., M. Eberstadt, E.T. Olejniczak, R.P. Meadows, and S.W. Fesik. NMR structure and mutagenesis of the Fas (APO-1/CD95) death domain.  Nature. 384, 638-641 (1996).
  12. Minn, A. J., P. Velez, S. L. Schendel, H. Liang, S. W. Muchmore, S. W. Fesik, M. Fill, and C. B. Thompson. Bcl-xL forms an ion channel in synthetic lipid membranes.  Nature. 385, 353-357 (1997).
  13. Sattler, M., H. Liang, D. Nettesheim, R.P. Meadows, J.E. Harlan, M. Eberstadt, H. Yoon, S.B. Shuker, B. Chang, A.J. Minn, C.B. Thompson, and S.W. Fesik. Structure of Bcl-xL/Bak peptide complex: Recognition between regulators of apoptosis.  Science. 275, 983-986 (1997).
  14. Hajduk, P. J., G. Sheppard, D. G. Nettesheim, E. T. Olejniczak, S. B. Shuker, R. P. Meadows, D. H. Steinman, G. M. Carrera, Jr., P. A. Marcotte, J. Severin, K. Walter, H. Smith, E. Gubbins, T. F. Holzman, D. W. Morgan, S. K. Davidsen, J. B. Summers, and S. W. Fesik. Discovery of potent nonpeptide inhibitors of stromelysin using SAR by NMR.  J. Am. Chem. Soc. 119, 5818-5827 (1997).
  15. Olejniczak, E. T., P. J. Hajduk, P. A. Marcotte, D. G. Nettesheim, R. P. Meadows, R. Edalji, T. F. Holzman, and S. W. Fesik. Stromelysin inhibitors designed from weakly bound fragments:  Effects of linking and cooperativity.  J. Am. Chem. Soc. 119, 5828-5832 (1997).
  16. Hajduk, P.J., R.P. Meadows, and S.W. Fesik. Discovering high-affinity ligands for proteins. Science. 278, 497-499 (1997).
  17. Eberstadt, M., B. Huang, Z. Chen, R. P. Meadows, S. Ng, L. Zheng, and S. W. Fesik. NMR structure and mutagenesis of the FADD (Mort1) death-effector domain.  Nature. 392, 941-945 (1998).
  18. Liu, X., H. Wang, M. Eberstadt, A. Schnuchel, E.T. Olejniczak, R.P. Meadows, J.M. Schkeryantz, D.A. Janowick, J.E. Harlan, E.A.S. Harris, D.E. Staunton, S.W. Fesik.  NMR     structure and mutagenesis of the N-terminal Dbl homology domain of the nucleotide exchange         factor Trio.  Cell. 95, 269-277 (1998).
  19. Sun, C., M. Cai, A. H. Gunasekera, R. P. Meadows, H. Wang, J. Chen, H. Zhang, W. Wu, N. Xu, S.-C. Ng, and S. W. Fesik.  NMR structure and mutagenesis of the inhibitor of apoptosis protein XIAP.  Nature. 401, 818-822 (1999).
  20. Fesik, S. W. Insights into Programmed Cell Death through Structural Biology. Cell. 103, 273-282 (2000).
  21. Fesik, S. W., and Y. Shi. Controlling the caspases.  Science. 294, 1477-1478 (2001).
  22. Riedl S. J., M. Renatus, R. Schwarzenbacher, Q. Zhou, C. Sun, S. W. Fesik, R. C. Liddington, and           G. S. Salvesen.  Structural basis for the inhibition of caspase-3 by XIAP.  Cell. 104, 791-800 (2001).
  23. Oltersdorf, T., S.W. Elmore, A.R. Shoemaker, R.C. Armstrong, D.J. Augeri, B.A. Belli, M. Bruncko, T.L. Deckwerth, J. Dinges, P.J. Hajduk, M.K. Joseph, S. Kitada, S.J. Korsmeyer, A.R. Kunzer, A. Letai, C. Li, M.J. Mitten, D.G. Nettesheim, S. Ng, P.M. Nimmer, J.M. O’Connor, A. Oleksijew, A.M. Petros, J.C. Reed, W. Shen, S.K. Tahir, C.B. Thompson, K.J. Tomaselli, B. Wang, M.D. Wendt, H. Zhang, S.W. Fesik and S.H. Rosenberg. An inhibitor of Bcl-2 family proteins induces regression of solid tumors. Nature. 435, 677-681 (2005).
  24. 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, 6140-6143 (2012).
  25. Friberg A, Vigil D, Zhao B, Daniels RN, Burke JP, Garcia-Barrantes P, Camper D, Chauder B, Lee T, Olejniczak ET, Fesik SW. Discovery of potent myeloid cell leukemia-1 (Mcl-1) inhibitors using fragment-based methods and structure-based design. J. Med. Chem. 56, 15-30 (2013).
  26. Frank A. O., Feldkamp M.D., Kennedy J. P., Waterson A. G., Pelz N. F., Patrone J. D., Vangamudi B., Camper D.V., Rossanese O. W., Chazin W. J., Fesik S.W. Discovery of a Potent Inhibitor of Replication Protein A Protein-Protein Interactions Using a Fragment Linking Approach. J. Med. Chem. 56, 9242-9250 (2013).
  27. Burns M.C., Sun Q., Daniels R.N., Camper D.V., Kennedy J. P., Phan, J., Olejniczak E. T., Lee T., Waterson A. G., Rossanese O. W., Fesik S.W. Approach for Targeting Ras with Small Molecules that Activate SOS-Mediated Nucleotide Exchange. Proceed. Natl. Acad. Sci. 111, 3401-3406 (2014).
  28. Sun Q., Phan J., Friberg A.R., Camper D.V., Olejniczak E.T., Fesik S.W. A method for the second-site screening of K-Ras in the presence of a covalently attached first-site ligand. J. Biomol. NMR. 60, 11-14 (2014).
  29. Thomas LR, Wang Q, Grieb BC, Phan J, Foshage AM, Sun Q, Olejniczak ET, Clark T, Dey S, Lorey S, Alicie B, Howard GC, Cawthon B, Ess KC, Eischen CM, Zhao Z, Fesik SW, Tansey WP. Interaction with WDR5 Promotes Target Gene Recognition and Tumorigenesis by MYC. Mol Cell. 58, 440-452 (2015).
  30. Burke J.P., Bian Z., Shaw S., Zhao B., Goodwin C.M., Belmar J., Browning C.F., Vigil D., Friberg A., Camper D.V., Rossanese O.W., Lee T., Olejniczak E.T., Fesik S.W. Discovery of tricyclic indoles that potently inhibit Mcl-1 using fragment-based methods and structure-based design. J. Med. Chem. 58, 3794-3805 (2015).
  31. Pelz N.F., Bian Z., Zhao B., Shaw S., Tarr J.C., Belmar J., Gregg C., Camper D.V., Goodwin C.M., Arnold A.L., Sensintaffar J.L., Friberg A., Rossanese O.W., Lee T., Olejniczak E.T., Fesik S.W. Discovery of 2-Indole-acylsulfonamide Myeloid Cell Leukemia 1 (Mcl-1) Inhibitors Using Fragment-Based Methods. J. Med. Chem. 59, 2054-2066 (2016).
  32. Erlanson D.A., Fesik S.W., Hubbard R.E., Jahnke W., Jhoti H. Twenty years on: the impact of fragments on drug discovery. Nat. Rev. Drug Discov. 15, 605-619 (2016).
  33. Lee T., Bian Z., Zhao B., Hogdal L.J., Sensintaffar J.L., Goodwin C.M., Belmar J., Shaw S., Tarr J.C., Veerasamy N., Matulis S.M., Koss B., Fischer M.A., Arnold A.L., Camper D.V., Browning C.F., Rossanese O.W., Budhraja A., Opferman J., Boise L.H., Savona M.R., Letai A., Olejniczak E.T., Fesik S.W. Discovery and Biological Characterization of Potent Myeloid Cell Leukemia-1 (Mcl-1) Inhibitors. FEBS Lett. 591, 240-251 (2017).
  34. Shaw S.*, Bian Z.*, Zhao B., Tarr J.C., Veerasamy N., Jeon K.O., Belmar J., Arnold A.L., Fogarty S.A., Perry E., Sensintaffar J.L., Camper D.V., Rossanese O.W., Lee T., Olejniczak E.T., Fesik S.W. Optimization of Potent and Selective Tricyclic Indole Diazepinone Myeloid Cell Leukemia-1 Inhibitors Using Structure-Based Design. J. Med. Chem. 61, 2410-2421 (2018).
  35. Howes J.E., Akan D.T., Burns M.C., Rossanese O.W., Waterson A.G., Fesik S.W. Small molecule-mediated activation of RAS elicits biphasic modulation of phospho ERK levels that are regulated through negative feedback on SOS1. Molecular Cancer Therapeutics Mol Cancer Ther. 17, 1051-1060 (2018).
  36. Abbott JR, Hodges TR, Daniels RN, Patel PA, Kennedy JP, Howes JE, Akan DT, Burns MC, Sai J, Sobolik T, Beesetty Y, Lee T, Rossanese OW, Phan J, Waterson AG, Fesik SW. Discovery of Aminopiperidine Indoles That Activate the Guanine Nucleotide Exchange Factor SOS1 and Modulate RAS Signaling. J. Med. Chem. 61, 6002-6017 (2018).
  37. Wang F, Jeon KO, Salovich JM, Macdonald JD, Alvarado J, Gogliotti RD, Phan J, Olejniczak ET, Sun Q, Wang S, Camper D, Yuh JP, Shaw JG, Sai J, Rossanese OW, Tansey WP, Stauffer SR, Fesik SW. Discovery of Potent 2Aryl-6,7-dihydro5Hpyrrolo[1,2a]imidazoles as WDR5-WIN-Site Inhibitors Using Fragment-Based Methods and Structure-Based Design. J. Med. Chem. 61, 5623−5642 (2018).
  38. Zhao B, Arnold AL, Coronel MA, Lee JH, Lee T, Olejniczak ET, Fesik SW. Understanding the Species Selectivity of Myeloid Cell Leukemia-1 (Mcl-1) Inhibitors. Biochemistry. 57, 4952-4958 (2018).
  39. Hodges TR, Abbott JR, Little AJ, Sarkar D, Salovich JM, Howes J, Akan DT, Sai J, Arnold AL, Browning C, Burns MC, Sobolik T, Sun Q, Beesetty Y, Coker J, Scharn D, Stadtmueller H, Rossanese OW, Phan J, Waterson AG, McConnell DB, Fesik SW. Discovery and Structure-Based Optimization of Benzimidazole-Derived Activators of SOS1-Mediated Nucleotide Exchange on RAS. J Med Chem. 61, 8875-8894 (2018).
  40. Abbott JR, Patel PA, Howes JE, Akan DT, Kennedy JP, Burns MC, Browning CF, Sun Q, Rossanese OW, Phan J, Waterson AG, Fesik SW. Discovery of Quinazolines That Activate SOS1-Mediated Nucleotide Exchange on RAS. ACS Med Chem Lett. 9, 941-946 (2018).
  41. Perry E, Mills JJ, Zhao B, Wang F, Sun Q, Christov PP, Tarr JC, Rietz TA, Olejniczak ET, Lee T, Fesik S. Fragment-based screening of programmed death ligand 1 (PD-L1). Bioorg Med Chem Lett. 29, 786-790 (2019).
  42. Akan DT, Howes JE, Sai J, Arnold AL, Beesetty Y, Phan J, Olejniczak ET, Waterson AG, Fesik SW. Small Molecule SOS1 Agonists Modulate MAPK and PI3K Signaling via Independent Cellular Responses. ACS Chem. Biol. 14, 325-331 (2019).
  43. Aho ER, Wang J, Gogliotti RD, Howard GC, Phan J, Acharya P, Macdonald JD, Cheng K, Lorey SL, Lu B, Wenzel S, Foshage AM, Alvarado J, Wang F, Shaw JG, Zhao B, Weissmiller AM, Thomas LR, Vakoc CR, Hall MD, Hiebert SW, Liu Q, Stauffer SR, Fesik SW, Tansey WP. Displacement of WDR5 from Chromatin by a WIN Site Inhibitor with Picomolar Affinity. Cell Rep. 26, 2916-2928 (2019).
  44. Lee T, Christov PP, Shaw S, Tarr JC, Zhao B, Veerasamy N, Jeon KO, Mills JJ, Bian Z, Sensintaffar JL, Arnold AL, Fogarty SA, Perry E, Ramsey HE, Cook RS, Hollingshead M, Davis Millin M, Lee KM, Koss B, Budhraja A, Opferman JT, Kim K, Arteaga CL, Moore WJ, Olejniczak ET, Savona MR, Fesik SW. Discovery of Potent Myeloid Cell Leukemia-1 (Mcl-1) Inhibitors That Demonstrate in Vivo Activity in Mouse Xenograft Models of Human Cancer. J. Med. Chem. 62, 3971-3988 (2019).
  45. Kessler D, Gmachl M., Mantoulidis A, Martin LJ, Zoephel A, Mayer M, Gollner A, Covini D, Fischer S, Gerstberger T, Gmaschitz T, Goodwin C, Greb P, Haering D, W, Hoffmann J, Karolyi-Oezguer J, P, Kornigg S, Koegl M, Kousek R, Lamarre L, Moser F, Munico-Martinez S, Peinsipp C, Phan J, Rinnenthal J, Sai J, Salamon C, Scherbantin Y, Schipany K, Schnitzer R, Schrenk A, Sharps B, Siszler G, Sun Q, Waterson AG, Wolkerstorfer B, Zeeb M, Pearson M, Fesik SW, McConnell DB. Drugging an “undruggable” pocket on KRAS. Proc. Natl. Acad. Sci. 116, 15823-15829 (2019).
  46. Aho ER, Weissmiller AM, Fesik SW, Tansey WP. Targeting WDR5: A WINning Anti-Cancer Strategy? Epigenet Insights. 12, 1-5 (2019).
  47. Macdonald J, Chacon Simon S, Han C, Wang F, Shaw JG, Howes J, Sai J, Yuh J, Camper D, Alicie B, Alvarado J, Nikhar S, Payne W, Aho ER, Bauer J, Zhao B, Phan J, Thomas L, Rossanese OW, Tansey WP, Waterson AG, Stauffer S, Fesik SW. Discovery and Optimization of Salicylic Acid-Derived Sulfonamide Inhibitors of the WD Repeat-Containing Protein 5 (WDR5)–MYC Protein–Protein Interaction (2019). J Med Chem. 62, 11232-11259 (2019).
  48. Thomas LR, Adams CM, Wang J, Weissmiller AM, Creighton J, Lorey SL, Liu Q, Fesik SW, Eischen CM, and Tansey WP. Interaction of the oncoprotein transcription factor MYC with its chromatin cofactor WDR5 is essential for tumor maintenance. Proc Natl. Acad. Sci. 116, 25260-25268 (2019).
  49. Tian J, Teuscher KB, Aho ER, Alvarado JR, Mills JJ, Meyers KM, Gogliotti RD, Han C, Macdonald JD, Sai J, Shaw JG, Sensintaffar JL, Zhao B, Rietz TA, Thomas LR, Payne WG, Moore WJ, Stott GM, Kondo J, Inoue M, Coffey RJ, Tansey WP, Stauffer SR, Lee T, Fesik SW. Discovery and Structure-Based Optimization of Potent and Selective WD Repeat Domain 5 (WDR5) Inhibitors Containing a Dihydroisoquinolinone Bicyclic Core. J. Med. Chem. 63, 656-675 (2020).
  50. Thomas LR, Adams CM, Fesik SW, Eischen CM, Tansey WP. Targeting MYC through WDR5. Mol Cell Oncol. 7. (2020).
  51. Kessler D, Gollner A, Gmachl M, Mantoulidis A, Martin LJ, Zoephel A, Mayer M, Covini D, Fischer S, Gerstberger T, Gmaschitz T, Goodwin C, Greb P, Häring D, Hela W, Hoffmann J, Karolyi-Oezguer J, Knesl P, Kornigg S, Koegl M, Kousek R, Lamarre L, Moser F, Munico-Martinez S, Peinsipp C, Phan J, Rinnenthal J, Sai J, Salamon C, Scherbantin Y, Schipany K, Schnitzer R, Schrenk A, Sharps B, Siszler G, Sun Q, Waterson A, Wolkerstorfer B, Zeeb M, Pearson M, Fesik SW, McConnell DB. Reply to Tran et al.: Dimeric KRAS protein-protein interaction stabilizers. Proc. Natl. Acad. Sci. 117, 3365-3367 (2020).
  52. Bryan AF, Wang J, Howard GC, Guarnaccia AD, Woodley CM, Aho ER, Rellinger EJ, Matlock BK, Flaherty DK, Lorey SL, Chung DH, Fesik SW, Liu Q, Weissmiller AM, Tansey WP. WDR5 is a conserved regulator of protein synthesis gene expression. Nucleic Acids Res. 48, 2924-2941 (2020).
  53. Chacón Simon S, Wang F, Thomas LR, Phan J, Zhao B, Olejniczak ET, Macdonald JD, Shaw JG, Schlund C, Payne W, Creighton J, Stauffer SR, Waterson AG, Tansey WP, Fesik SW. Discovery of WD Repeat-Containing Protein 5 (WDR5)-MYC Inhibitors Using Fragment-Based Methods and Structure-Based Design. J. Med. Chem. 63, 4315-4333 (2020).
  54. Sarkar D, Olejniczak ET, Phan J, Coker JA, Sai J, Arnold AL, Beesetty Y, Waterson AG, Fesik SW. Discovery of Sulfonamide-Derived Agonists of SOS1-Mediated Nucleotide Exchange on RAS Using Fragment-Based Methods. J. Med. Chem. 63, 8325-8337 (2020).
  55. Guarnaccia AD, Rose KL, Wang J, Zhao B, Popay TM, Wang CE, Guerrazzi K, Hill S, Woodley CM, Hansen TJ, Lorey SL, Shaw JG, Payne WG, Weissmiller AM, Olejniczak ET, Fesik SW, Liu Q, Tansey WP. Impact of WIN site inhibitor on the WDR5 interactome. Cell Rep. 34, 1-50 (2021).
  56. Rietz TA, Teuscher KB, Mills JJ, Gogliotti RD, Lepovitz LT, Scaggs WR, Yoshida K, Luong K, Lee T, Fesik SW. Fragment-Based Discovery of Small Molecules Bound to T-Cell Immunoglobulin and Mucin Domain-Containing Molecule 3 (TIM-3). J. Med. Chem. 64, 14757-14772 (2021).
  57. Siladi AJ, Wang J, Florian AC, Thomas LR, Creighton JH, Matlock BK, Flaherty DK, Lorey SL, Howard GC, Fesik SW, Weissmiller AM, Liu Q, Tansey WP. WIN site inhibition disrupts a subset of WDR5 function. Sci. Rep. 12, 1848 (2022).
  58. Teuscher KB, Meyers KM, Wei Q, Mills JJ, Tian J, Alvarado J, Sai J, Van Meveren M, South TM, Rietz TA, Zhao B, Moore WJ, Stott GM, Tansey WP, Lee T, Fesik SW. Discovery of Potent Orally Bioavailable WD Repeat Domain 5 (WDR5) Inhibitors Using a Pharmacophore-Based Optimization. J. Med. Chem. 65, 6287-6312 (2022).
  59. Joachim Bröker*, Alex G. Waterson*, Chris Smethurst, Dirk Kessler, Jark Böttcher, Moriz Mayer, Gerhard Gmaschitz, Jason Phan, Andrew Little, Jason R. Abbott, Qi Sun, Michael Gmachl, Dorothea Rudolph, Heribert Arnhof, Klaus Rumpel, Fabio Savarese, Thomas Gerstberger, Nikolai Mischerikow, Matthias Treu, Lorenz Herdeis, Tobias Wunberg, Andreas Gollner, Harald Weinstabl, Andreas Mantoulidis, Oliver Krämer, Darryl B. McConnell, and Stephen W. Fesik. Fragment Optimization of Reversible Binding to the Switch II Pocket on KRAS Leads to a Potent, In Vivo Active KRASG12C Inhibitor. J. Med. Chem. 65, 14614-14629 (2022).
  60. Kevin B. Teuscher, Somenath Chowdhury, Kenneth M. Meyers, Jianhua Tian, Jiqing Sai, Mayme Van Meveren, Taylor M. South, John L. Sensintaffar, Tyson A. Rietz, Soumita Goswami, Jing Wang, Brian C. Grieb, Shelly L. Lorey, Gregory C. Howard, Qi Liu, William J. Moore, Gordon M. Stott, William P. Tansey, Taekyu Lee, and Stephen W. Fesik. Structure-Based Discovery of Potent WD Repeat Domain 5 Inhibitors that Demonstrate Efficacy and Safety in Preclinical Animal Models. Proceed. Natl. Acad. Sci. 120, (2023).
  61. 62. Teuscher K., Mills J., Chango Han J.T., Meyers K., Sai J., South, T., Crow M., Van Meveren M., Sensintaffar J., Zhao B., Amporndanai K., Moore W., Stott G., Tansey W., Lee T., Fesik S. .  Structure-Based Discovery of Potent Orally Bioavailable Benzoxazepinone-Based WD Repeat Domain 5 Inhibitors. J. Med. Chem. (2024).
  62. Weissmiller A.W., Fesik S.W., Tansey W.P. WD Repeat Domain 5 Inhibitors for Cancer: Not What You Think. J. Clin. Med. 13, 274 (2024)