Stephen Frye, PhD

Director Fred Eshelman Distinguished Professor

Stephen Frye is a professor and director of the Center for Integrative Chemical Biology and Drug Discovery at the University of North Carolina in Chapel Hill. Frye is also the lead principal investigator for the North Carolina Comprehensive Chemical Biology Center, a UNC-based, NCI designated center that engages in oncology drug discovery. His research focuses on chemical biology of chromatin regulation and drug discovery.

After obtaining a BS in chemistry at North Carolina State University in 1983, Frye joined the laboratory of Professor Ernest Eliel at UNC-Chapel Hill. Frye’s research at UNC focused on asymmetric synthesis and included an off-campus research fellowship in Lausanne, Switzerland, to investigate mechanisms of stereoselective organometallic reactions via NMR kinetics.

Upon completing his PhD in 1987, Frye began his professional career as a medicinal chemist at the newly initiated US research site for Glaxo, located at that time in temporary facilities in Venable Hall on the UNC campus. He subsequently led the project that resulted in Avodart, GlaxoSmithKline’s dual 5a-reductase inhibitor for treatment of benign prostatic hyperplasia. The drug is currently under investigation for the prevention of prostate cancer.

Shortly after Glaxo merged with Wellcome in 1995, Frye established a new chemistry department in Research Triangle Park based upon kinase target class science and GSK’s kinase inhibitors. Tykerb (a dual erbB2/EGFR inhibitor approved for the treatment of metastatic breast cancer) and Pazopanib (approved for renal carcinoma) were discovered within this department. In 1999 he began a secondment at GW’s Stevenage site in the United Kingdom leading a research unit in medicinal chemistry. Following the merger with GSK in the spring of 2000, he was selected to lead GSK’s High Throughput Chemistry Group that evolved into Discovery Medicinal Chemistry (DMC).

Over the seven years Frye led DMC, the group grew to more than 200 chemists and developed global target-class chemical science and a compound collection strategy that enhanced both the productivity and quality of GSK’s hit and lead generation across all therapeutic areas. Stephen joined the UNC School of Pharmacy in October 2007 to create the CICBDD in cooperation with the Lineberger Comprehensive Cancer Center, the School of Medicine, and the Department of Chemistry.

Research

The Center for Integrative Chemical Biology and Drug Discovery was created with the mission of bringing dedicated medicinal chemistry expertise to bear on biological targets of therapeutic relevance under investigation by UNC faculty. Synthetic chemists, assay development and compound profiling scientists will work in the Center and create dedicated, multidisciplinary project teams with other groups on campus in order to progress targets through the drug discovery and development process.

Education, Certification and Licensure

American University, Washington, D.C., October 1997 to December 1998
Graduate certificate in Organizational Change-Leadership

University of North Carolina at Chapel Hill, 1983 to 1987
Major: Organic Chemistry, Adviser: Professor Ernest L. Eliel
PhD, May 1987, Dissertation: “Stereoselective Syntheses Based on Chiral 1,3-Oxathianes: Synthesis of Mevalolactone and Citramalic Acid and Investigation of the Mechanism of Diastereoselection”

Off-Campus Graduate Fellow, Institut de Chemie Organique, de Université de Lausanne, Switzerland, March to September 1986

North Carolina State University, 1979-1983
Major: Chemistry, Minor: Polymer/Textile Chemistry
BS, Summa Cum Laude with Honors, May 1983

Publications

  • “Identification of a Fragment-like Small Molecule Ligand for the Methyl-lysine Binding Protein, 53BP1”, Perfetti, M. T.; Baughman, B. M.; Dickson, B. M.; Mu, Y.; Cui, G.; Mader, P.; Dong, A.; Norris, J. L.; Rothbart, S. B.; Strahl, B. D.; Brown, P. J.; Janzen, W. P.; Arrowsmith, C. H.; Mer, G.; McBride, K. M.; *James, L. I.; *Frye, S. V. ACS Chem Biol 2015 DOI: 10.1021/cb500956g.
  • “Tumor endothelial cells with distinct patterns of TGFβ-driven endothelial-to-mesenchymal transition”, Xiao, L.; Kim, D. J.; Davis, C. L.; McCann, J. V.; Dunleavey, J. M.; Vanderlinden, A.; Xu, N.; Pattenden, S. G.; Frye, S. V.; Xu, X.; Onaitis, M.; Monaghan-Benson, E.; Burridge, K.; Dudley, A. C. Cancer Research 2015 DOI: 10.1158/0008-5472.can-14-1616.
  • “Selective inhibition of EZH2 and EZH1 enzymatic activity by a small molecule suppresses MLL-rearranged leukemia”, Xu, B.; On, D. M.; Ma, A.; Parton, T.; Konze, K. D.; Pattenden, S. G.; Allison, D. F.; Cai, L.; Rockowitz, S.; Liu, S.; Liu, Y.; Li, F.; Vedadi, M.; Frye, S. V.; Garcia, B. A.; Zheng, D.; Jin, J.; Wang, G. G. Blood 2015, 125, 346-357.
  • “Mer Receptor Tyrosine Kinase: Therapeutic Opportunities in Oncology, Virology, and Cardiovascular Indications”, Wang, X.; Frye*, S. Annual Reports in Med. Chemistry 2014, 49, 301-314.
  • “UNC2025, a Potent and Orally Bioavailable MER/FLT3 Dual Inhibitor”, Zhang, W.; DeRyckere, D.; Hunter, D.; Liu, J.; Stashko, M. A.; Minson, K. A.; Cummings, C. T.; Lee, M.; Glaros, T. G.; Newton, D. L.; Sather, S.; Zhang, D.; Kireev, D.; Janzen, W. P.; Earp, H. S.; Graham, D. K.; *Frye, S. V.; *Wang, X. J Med Chem 2014, 57, 7031. PMID: 25068800. PMCID: PMC4148167.
  • “Discovery of a Selective, Substrate-Competitive Inhibitor of the Lysine Methyltransferase SETD8”, Ma, A.; Yu, W.; Li, F.; Bleich, R. M.; Herold, J. M.; Butler, K. V.; Norris, J. L.; Korboukh, V.; Tripathy, A.; Janzen, W. P.; Arrowsmith, C. H.; Frye, S. V.; Vedadi, M.; Brown, P. J.; *Jin, J. J of Med Chem 2014, 57, 6822-6833.
  • “The Lipid Kinase PIP5K1C Regulates Pain Signaling and Sensitization”, Wright, B. D.; Loo, L.; Street, S. E.; Ma, A.; Taylor-Blake, B.; Stashko, M. A.; Jin, J.; Janzen, W. P.; Frye, S. V.; Zylka*, M. J. Neuron 2014, 82, 836-47. PMID: 24853942. PMCID: PMC4074510.
  • “Pseudo-Cyclization through Intramolecular Hydrogen Bond Enables Discovery of Pyridine Substituted Pyrimidines as New Mer Kinase Inhibitors”, Zhang, W.; Zhang, D.; Stashko, M. A.; Deryckere, D.; Hunter, D.; Kireev, D.; Miley, M. J.; Cummings, C.; Lee, M.; Norris-Drouin, J.; Stewart, W. M.; Sather, S.; Zhou, Y.; Kirkpatrick, G.; Machius, M.; Janzen, W. P.; Earp, H. S.; Graham, D. K.; Frye, S. V.; Wang, X.*, J Med Chem 2013. DOI. 10.1021/jm401387j. PMID: 24195762.
  • “Discovery of Mer Specific Tyrosine Kinase Inhibitors for the Treatment and Prevention of Thrombosis”, Zhang, W.; McIver, A. L.; Stashko, M. A.; Deryckere, D.; Branchford, B. R.; Hunter, D.; Kireev, D.; Miley, M. J.; Norris-Drouin, J.; Stewart, W. M.; Lee, M.; Sather, S.; Zhou, Y.; Di Paola, J. A.; Machius, M.; Janzen, W. P.; Earp, H. S.; Graham, D. K.; Frye, S. V.; Wang, X.* J Med Chem 2013. DOI.10.1021/jm4013888. PMID: 24219778.
  • “UNC569, a Novel Small-Molecule Mer Inhibitor with Efficacy against Acute Lymphoblastic Leukemia In Vitro and In Vivo”, Christoph, S.; DeRyckere, D.; Schlegel, J.; Frazer, J. K.; Batchelor, L. A.; Trakhimets, A. Y.; Sather, S.; Hunter, D. M.; Cummings, C. T.; Liu, J.; Yang, C.; Kireev, D.; Simpson, C.; Norris-Drouin, J.; Hull-Ryde, E. A.; Janzen, W. P.; Johnson, G. L.; Wang, X.; Frye, S. V.; Earp III, H. S.; Graham, D. K., Mol. Cancer Therap. 2013, 12 (11), 2367-2377. PMID: 23997116.