Stephen Frye, PhD
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.
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 the 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 (in Phase III trials 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.
10 Most Recent Publications
- “Discovery of a chemical probe for the L3MBTL3 methyl-lysine reader domain”, James, L. I.; Barsyte-Lovejoy, D.; Zhong, N.; Krichevsky, L.; Korboukh, V. K.; Herold, J.; MacNevin, C. J.; Norris, J. L.; Sagum, C. C.; Tempel, W.; Marcon, E.; Guo, H.; Gao, C.; Huang, X-P.; Kireev, D. B.; Jin, J.; Greenblatt, J.; Janzen, W. P.; Brown, P. J.; Bedford, M. T.; *Arrowsmith, C. H.; *Frye, S. V. Nature Chem. Bio. advance online publication, DOI: 10.1038/nchembio.1157.
- “Orally Active Adenosine A1 Receptor Agonists with Antinociceptive Effects in Mice”, Korboukh, I.; Hull-Ryde, E. A.; Rittiner, J. E.; Randhawa, A. S.; Coleman, J.; Fitzpatrick, B. J.; Setola, V.; Janzen, W. P.; Frye, S. V.; *Zylka, M. J.; *Jin, J. Journal of Medicinal Chemistry 2012, 55, 6467-6477.
- “Dynamic Reprogramming of the Kinome In Response to Targeted MEK Inhibition In Triple Negative Breast Cancer”, Duncan, J. S.; Whittle, M. C.; Nakamura, K.; Abell, A. N.; Midland, A. A.; Zawistowski, J. S.; Johnson, N. L.; Granger, D. A.; Jordan, N. V.; Darr, D. B.; Usary, J.; Kuan, P.-F.; Smalley, D. M.; Major, B.; He, X.; Hoadley, K.; Sharpless, N. E.; Perou, C. M.; Gomez, S. M.; Chen, X.; Jin, J.; Frye, S. V.; Earp, H. S.; Graves, L. M.; Johnson, G. L.* Cell 2012, 149, 307-321.
- “AMP Is an Adenosine A1 Receptor Agonist”, Rittiner, J. E.; Korboukh, I.; Hull- Ryde, E.; Jin, J.; Janzen, W. P.; Frye, S. V.; *Zylka, M. J. J. Bio. Chem. 2012,
- Discovery of β-arrestin-biased dopamine D2 ligands for probing signal transduction pathways essential for antipsychotic efficacy. Allen JA, Yost JM, Setola V, Chen X, Sassano MF, Chen M, Peterson S, Yadav PN, Huang XP, Feng B, Jensen NH, Che X, Bai X, Frye SV, Wetsel WC, Caron MG, Javitch JA, Roth BL, Jin J. Proc Natl Acad Sci U S A. 2011 Nov 8;108(45):18488 93. Epub 2011 Oct 24. PMID: 22025698 [PubMed - indexed for MEDLINE]
- Drug discovery toward antagonists of methyl-lysine binding proteins. Herold JM, Ingerman LA, Gao C, Frye SV. Curr Chem Genomics. 2011;5:51-61. Epub 2011 Aug 22. PMID: 22145013
- The nucleotide AMP is an adenosine A1 receptor agonist. Rittiner JE, Korboukh I, Hull-Ryde EA, Jin J, Janzen WP, Frye SV, Zylka MJ. J Biol Chem. 2012 Jan 3. [Epub ahead of print] PMID: 22215671
- Optimization of Cellular Activity of G9a Inhibitors 7-Aminoalkoxy-quinazolines. Liu F, Barsyte-Lovejoy D, Allali-Hassani A, He Y, Herold JM, Chen X, Yates CM, Frye SV, Brown PJ, Huang J, Vedadi M, Arrowsmith CH, Jin J. J Med Chem. 2011 Sep 8;54(17):6139-50. Epub 2011 Aug 5. PMID: 21780790
- A chemical probe selectively inhibits G9a and GLP methyltransferase activity in cells. Vedadi M, Barsyte-Lovejoy D, Liu F, Rival-Gervier S, Allali-Hassani A, Labrie V, Wigle TJ, Dimaggio PA, Wasney GA, Siarheyeva A, Dong A, Tempel W, Wang SC, Chen X, Chau I, Mangano TJ, Huang XP, Simpson CD, Pattenden SG, Norris JL, Kireev DB, Tripathy A, Edwards A, Roth BL, Janzen WP, Garcia BA, Petronis A, Ellis J, Brown PJ, Frye SV, Arrowsmith CH, Jin J. Nat Chem Biol. 2011 Aug 17;7(9):648. doi: 10.1038/nchembio0911-648c. No abstract available. PMID: 21850000
- A chemical probe selectively inhibits G9a and GLP methyltransferase activity in cells. Vedadi M, Barsyte-Lovejoy D, Liu F, Rival-Gervier S, Allali-Hassani A, Labrie V, Wigle TJ, Dimaggio PA, Wasney GA, Siarheyeva A, Dong A, Tempel W, Wang SC, Chen X, Chau I, Mangano TJ, Huang XP, Simpson CD, Pattenden SG, Norris JL, Kireev DB, Tripathy A, Edwards A, Roth BL, Janzen WP, Garcia BA, Petronis A, Ellis J, Brown PJ, Frye SV, Arrowsmith CH, Jin J. Nat Chem Biol. 2011 Jul 10;7(8):566-74. doi: 10.1038/nchembio.599. PMID: 21743462