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Stephen v. frye

Stephen V. Frye
CURRICULUM VITAE

PERSONAL


UNC Eshelman School of Pharmacy Office: 919 843-5486 The University of North Carolina at Mobile: 919 260 3118 Chapel Hill Genetic Medicine Building Campus Box 7363 Chapel Hill, NC 27599-7363 Born March 8, 1961 in Greensboro, North Carolina
Married for 29 years to Susan B. Frye
and have three children (Aaron 22,
Jeremy 21, Rachel 16).

EDUCATION

American University, Washington DC, Oct. 1997- Dec. 1998 Graduate certificate in Organizational Change-Leadership University of North Carolina at Chapel Hill, 1983 -1987 Major: Organic Chemistry Advisor: Prof. Ernest L. Eliel Ph.D. 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-September 1986 North Carolina State University, 1979-1983 Major: Chemistry Minor: Polymer/Textile Chemistry B.S. Summa Cum Laude with Honors, May 1983
PROFESSIONAL EXPERIENCE

University of North Carolina at Chapel Hill
Fred Eshelman Distinquished Professor, Division of Medicinal Chemistry, and Director, Center for Integrative Chemical Biology and Drug Discovery School of Pharmacy (June 2012 - present) Professor, Division of Medicinal Chemistry, and Director, Center for Integrative Chemical Biology and Drug Discovery School of Pharmacy (Nov. 2011 – May 2012) Research Professor, Division of Medicinal Chemistry, and Director, Center for Integrative Chemical Biology and Drug Discovery School of Pharmacy (2007- Nov. 2011) Member, Molecular Therapeutics, Lineberger Comprehensive Cancer Center Adjunct Professor, Department of Chemistry Key Responsibilities – Responsible for vision, creation and productivity of a new research center at UNC focussed on chemical biology and drug discovery.
Glaxo, Glaxo-Wellcome and GlaxoSmithKline
(1987-2007)
Key Drug Discovery Accomplishments while employed at GSK:
 Project leader and co-inventor of GSK's 5-reductase inhibitor (Avodart, dutasteride; FDA approved for treatment of benign prostatic hyperplasia; > $1 billion world-wide sales in 2010).  Created a global kinase chemistry team that discovered Tykerb (dual erbB2 and EGFR inhibitor, approved for the treatment of metastatic breast cancer) and Pazopanib (VEGF inhibitor approved for the treatment of renal carcinoma). Scientific, Management and Leadership Roles:

World Wide Vice President, High Throughput Chemistry & Discovery
Medicinal Chemistry
, Molecular Discovery Research, GSK (July 2000-
August 2007)
Key Responsibilities – lead staff of up to 200 internal chemists and >100 external chemists accountable for all hit to lead and prospective compound collection building chemistry globally in GSK. Budget responsibility for $50M operational and $3-5M capital per annum. Research Unit Head, Chemistry Division, Glaxo Wellcome R&D,
Stevenage, UK (overseas assignment, July 1999-July 2000)
Department Head, Medicinal Chemistry, Glaxo Wellcome Inc., RTP
(January 1998 – July 1999)
Principal Research Scientist, Glaxo Wellcome Inc., RTP (February 1997
– December 1997)
Department Head, Medicinal Chemistry, Glaxo Wellcome Inc., RTP (July
1995 - February 1997)
Senior Research Investigator II, Chairman of the Cancer Scientific
Forum, Glaxo Research Institute, Department of Medicinal Chemistry,
RTP (September 1994 - July 1995)
Senior Research Investigator and Project Leader, Glaxo Research
Institute, Department of Medicinal Chemistry, RTP (January 1991-
September 1994)
Senior Scientist, Glaxo Research Institute, Department of Medicinal
Chemistry, RTP (August 1987-January 1991)
Adjunct Assistant Professor, University of North Carolina at Chapel Hill,
Department of Chemistry (January 1990-January 1995)

Honors, Fellowships & Awards

CEO's Award 1993, Glaxo Research Institute (Special award for leadership of the 5-reductase project that led to Avodart) American Chemical Society, Organic Division Fellowship 1986-87 University of North Carolina, Off Campus Graduate Fellowship 1986 University of North Carolina, Board of Governor's Fellowship in Science and Technology 1985-86 University of North Carolina, Department of Chemistry, Dobbins Fellowship 1984 University of North Carolina, Department of Chemistry, Reilley Fellowship 1983
Consulting Activities (2007-2011)
Astex Inc. Intellikine Inc. Kainos Medicine Inc. Integrated Oncology Solutions Inc. Proteostasis Therapeutics Inc. Sirga Advanced Biopharma Inc. Syndexa Inc. Novartis Option Fund New Leaf Ventures Inc. Sanofi-Aventis Eli Lilly BIBLIOGRAPHY

Publications
(*corresponding author)
Recent solicited contributions: 1) "Too many roads not taken", *Edwards, A.; Isserlin, R.; Bader, G.; Frye, S.; Willson, T.; Yu, F., Commentary Nature 2011, 470 (7333), p. 163-165.
2) "The art of the chemical probe", *Frye, S., Commentary, Nature Chem. Bio., 2010
6(3): p. 159-161, (Cited by Faculty of 1000).
3) "Epigenetics: tools and technologies", *Janzen, W., Wigle, T., Jin, J. & Frye, S., Drug Discovery Today: Technologies 2010 7, e59-e65.
4) "Inhibitors paradoxically prime kinases", *Frye, S.; Johnson, G., News and Views, Nature Chem. Bio., 2009 5(7): p. 448-449.
5) "Why Academic Drug Discovery?" *Frye, S.; Janzen, B., Editorial for Future Pharma, August 2009.
Peer reviewed publications/reviews:
Based on research in current role at UNC

6) "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.
7) "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,
287, 5301-5309.
8) "Discovery of Small Molecule Mer Kinase Inhibitors for the Treatment of Pediatric Acute Lymphoblastic Leukemia", Liu, J.; Yang, C.; Simpson, C.; DeRyckere, D.; Van Deusen, A.; Miley, M. J.; Kireev, D.; Norris-Drouin, J.; Sather, S.; Hunter, D.;
Korboukh, V. K.; Patel, H. S.; Janzen, W. P.; Machius, M.; Johnson, G. L.; Earp,
H. S.; Graham, D. K.; Frye, S. V.; *Wang, X. ACS Medicinal Chemistry Letters
2012, dx.doi.org/10.1021/ml200239k.
9) "Structure-Activity Relationships of Methyl-Lysine Reader Antagonists", Herold, J.; Ingerman James, L.; Korboukh, V.; Gao, C.; Coil, K.; Bua, D.; Norris, J.;
Brown, P.; Jin, J.; Janzen, W.; Gozani, O.; *Frye, S., Medicinal Chemistry
Communications
2012, 3, 45-51.
10) "Discovery of beta-Arrestin-Biased Dopamine D2 Ligands for Probing Signal Transduction Pathways Essential for Antipsychotic Efficacy", Allen, J. A.; Yost, J.
M.; Setola, V.; Chen, X.; Sassano, M. F.; Chen, M.; Peterson, S.; Yadav, P. N.;
Huang, X. P.; Feng, B.; Jensen, N. H.; Che, X.; Bai, X.; Frye, S. V.; Wetsel, W.
C.; Caron, M. G.; Javitch, J. A.; *Roth, B. L.; *Jin, J. Proc Natl Acad Sci U S A
2011, 108, 18488.
11) "Optimization of Cellular Activity of G9a Inhibitors 7-Aminoalkoxy-quinazolines", Liu, F.; Barsyte-Lovejoy, D.; Allali-Hassani, A.; He, Y.; Herold, J. M.; Chen, X.;
Yates, C. M.; Frye, S. V.; Brown, P. J.; Huang, J.; Vedadi, M.; *Arrowsmith, C. H.;
*Jin, J. J. Med. Chem. 2011, 54, 6139-50. PMID: 21780790.
12) "US Academic Drug Discovery", *Frye, S.; Crosby, M.; Edwards, T.; *Juliano, R., Nature Rev. Drug Disc. 2011, 10, 409-10.
13) "A Chemical Probe Selectively Inhibits G9a and GLP Methyltransferase Activity in Cells", Vedadi, M.; Barsyte-Lovejoy, D.; Liu, F.; Allali-Hassan, A.; Rival-
Gervier, S.; Wigle, T.; DiMaggio, P.; Wasney, G.; Siarheyeva, A.; Dong, A.;
Tempel, W.; Chen, X.; Chau, I.; Mangano, T.; Evans, J.; Simpson, C. D.;
Pattenden, S.; Norris, J.; Kireev, D.; Tripathy, A.; Edwards, A.; Roth, B.; Janzen,
W.; Garcia, B.; Ellis, J.; Brown, P.; Frye, S.; *Arrowsmith, C.; *Jin, J., Nature
Chem. Bio. 2011, 7, 566-74.
14) "Drug Discovery Toward Antagonists of Methyl-lysine Binding Proteins", Herold, J.; Ingerman, L.; Gao, C.; *Frye, S., Current Chem. Genomics 2011, 5, (suppl. 1-
M2) 51-61.
15) "Small Molecule Ligands of Methyl-Lysine Binding Proteins", Herold, J. M.; Wigle, T.; Norris, J.; Lam, R.; Korboukh, V.; Gao, C.; Ingerman, L.; Kireev, D.;
Senisterra, G.; Vedadi, M.; Tripathy, A.; Brown, P.; Arrowsmith, C.; Jin, J.;
Janzen, W.; *Frye, S., J. Med. Chem. 2011, 54, 2504–251.
16) "Biophysical probes reveal a ‘compromise' recognition of histone methylation states by MBT domains", Gao, C.; Herold, J.; *Kireev, D; Wigle, T.; Norris, J.;
Frye, S., J. Am. Chem. Soc., 2011, 133 (14), 5357-5362.
17) "Oncometabolite 2-Hydroxyglutarate Is a Competitive Inhibitor of -Ketoglutarate- Dependent Dioxygenases", Xu, W.; Yang, H.; Liu, Y.; Yang, Y.; Wang, P.; Kim,
S.-H.; Ito, S.; Yang, C.; Wang, P.; Xiao, M.-T.; Liu, L.-x.; Jiang, W.-q.; Liu, J.;
Zhang, J.-y.; Wang, B.; Frye, S.; Zhang, Y.; Xu, Y.-h.; Lei, Q.-y.; Guan, K.-L.;
Zhao, S.-m.; *Xiong, Y., Cancer Cell 2011, 19 (1), 17-30 (cover story).
18) "Identification of Non-Peptide Malignant Brain Tumor (MBT) Repeat Antagonists by Virtual Screening of Commercially Available Compounds", Kireev*, D.; Wigle,
T.; Norris-Drouin, J.; Herold, J.; Janzen, W.; Frye, S., J. Med. Chem. 2010, 53,
7625-7631.
19) "Targeting Methyl-Lysine", Frye*, S.; Heightman, T.; Jin, J., Annual Reports in Med. Chemistry 2010, 45, 329-343.
20) "Accessing Protein Methyltransferase and Demethylase Enzymology Using Microfluidic Capillary Electrophoresis", Wigle, T.; Provencher, L.; Norris, J.; Jin,
J.; Brown, P.; Frye, S.; *Janzen, W., Chemistry and Biology 2010, 17, 695-704
(cover story).
21) "Protein Lysine Methyltransferase G9a Inhibitors: Design, Synthesis, and Structure Activity Relationships of 2,4-Diamino-7-aminoalkoxy-quinazolines", Liu,
F.; Chen, X.; Allali-Hassani, A.; Quinn, M.; Wigle, T.; Wasney, G.; Dong, A.;
Senisterra, G.; Chau, I.; Siarheyeva, A.; Norris, J.; Kireev, D.; Jadhav, A.; Herold,
J.; Janzen, W.; Arrowsmith, S.; Frye, S.; Brown, P.; Simeonov, A.; Vedadi, M.;
*Jin, J., J. Med. Chem., 2010, 53, 5844-5857.
22) "Screening for Inhibitors of Low Affinity Epigenetic Peptide-Protein Interactions: An AlphaScreen™-Based Assay for Antagonists of Methyl-Lysine Binding
Proteins", Wigle, T.; Herold, J. M.; Kireev, D.; Frye, S.; *Janzen, W., J.
Biomolecular Screening
2010, 15, 62-71 (cover story).
23) "Discovery of a 2,4-Diamino-7-aminoalkoxyquinazoline as a Potent and Selective Inhibitor of Histone Lysine Methyltransferase G9a", Feng, L.; Chen, X.; Allali-
Hassani, A.; Quinn, A.; Wasney, G.; Dong, A.; Barsyte, D.; Kozieradzki, I.;
Senisterra, G.; Chau, I.; Siarheyeva, A.; Kireev, D.; Jadhav, A.; Herold, J. M.;
Frye, S.; Arrowsmith, C.; Brown, P.; Simeonov, A.; Vedadi, M.; *Jin, J., J. Med.
Chem.,
2009, 52(24): p. 7950-3.
Based on research at GSK 24) "Photochemical Rearrangement of a 6-Azasteroid Oxaziridine to a Novel 17- Carbomethoxy-A-homo-B-seco-6-aza-3, 5-androstanedione", *Frye, S., J.
Mexican Chemical Society (special commemorative issue in honor of Ernest
Eliel)
2009, 53(3): p. 131-133.
25) "Discovery and Development of Dutasteride, a Potent Dual 5-Reductase Inhibitor", *Frye, S., Current Topics in Medicinal Chemistry 2006, 6, 405-421.
26) "A prodrug approach to the design of cRaf1 kinase inhibitors with improved cellular activity", Wood, E.; Crosby, R.; Dickerson, S.; Frye, S.; Griffin, R.;
Hunter, R.; Jung, D.; McDonald, O. B.; McNutt, R.; Mahony, W.; Peel, M.; Ray,
J.; *Lackey, K., Anti-Cancer Drug Design 2001, 16(1), 1-6.
27) "Oxindole-Based Inhibitors of Cyclin-Dependent Kinase 2 (CDK2): Design, Synthesis, Enzymatic Activities, and X-ray Crystallographic Analysis",
Bramson, H. N.; Corona, J.; Davis, S.; Dickerson, S.; Edelstein, M.; Frye, S.;
Gampe, Jr., R.; Harris, P.; Hassell, A.; Holmes, W.; Hunter, R.; Lackey, K.;
Lovejoy, B.; Luzzio, M.; Montana, V.; Rocque, W.; Rusnak, D.; Shewchuk, L.;
Veal, J.; Walker, D.; *Kuyper, L., J. Med. Chem., 2001, 44(25), 4339-4358.
28) "The discovery of potent cRaf1 kinase inhibitors", *Lackey, K.; Cory, M.; Davis, R.; Frye, S.; Harris, P.; Hunter, R.; Jung, D.; McDonald, O. B.; McNutt, R.; Peel, M.;
Rutkowske, R.; Veal, J.; Wood, E., Bioorg. Med. Chem. Lett. 2000, 10(3), 223-226.
29) "Structure-Activity Relationship Homology (SARAH): A Conceptual Framework for Drug Discovery in the Genomic Era", *Frye, S., Chemistry & Biology, 1999, 6,
R3-R7.
30) "TNFconverting enzyme", *Moss, M.; *Becherer, J. D.; Milla, M.; Pahel, G.; Lambert, M.; Andrews, R.; Frye, S.; Haffner, C.; Cowan, D.; Maloney, P.; Dixon, E.;
Jansen, M.; Vitek, M.; Mitchell, J.; Leesnitzer, T.; Warner, J.; Conway, J.; Bickett, D.
M.; Bird, M.; Priest, R.; Reinhard, J.; Lin, P., In Metalloproteinases Targets Anti-
Inflammatory Drugs;
Kevin M. K. Bottomley, David Bradshaw; John S. Nixon, Eds.;
Birkhaeuser Verlag, Basel, Switz 1999, 187-203.
31) "Discovery and Development of GG745, a Potent Inhibitor of Both Isozymes of -Reductase", *Frye, S.; Bramson, H. N.; Hermann, D.; Lee, F.; Sinhababu, A.;
Tian, G., In Integration of Pharmaceutical Discovery and Development: Case
Histories
; R.T. Borchardt, R.M. Freidinger, T. Sawyer and P. Smith, Eds.; Plenum
Press;1998, 11, 393-422.
32) "The Unique Preclinical Characteristics of GG745, A Potent Dual Inhibitor of 5- Reductase", *Bramson, H. N.; Hermann, D.; Batchelor, K.; Lee, F.; James, M.;
Frye, S., J. Pharm. Exp. Ther., 1997, 282, 1496-1502.
33) "Inhibition of Human Steroid 5-Reductases type I and II by 6-Aza-Steroids: Structural Determinants of One-Step vs Two-Step Mechanism", *Moss, M.;
Kuzmic, P.; Stuart, J. D.; Tian, G.; Peranteau, A.; Frye, S.; Kadwell, S.; Kost, T.;
Overton, L.; Patel, I., Biochemistry, 1996, 35, 3457-3464.
34) "Inhibitors of 5-Reductase", *Frye, S., Current Pharmaceutical Design, 1996, 2,
35) "Mechanism of Time -Dependent Inhibition of 5-Reductases by 1-4- Azasteroids: Toward Perfection of Rates of Time-Dependent Inhibition by Using
Ligand Binding Energies", *Tian, G.; Mook, Jr., R.; Moss, M.; Frye, S.,
Biochemistry, 1995, 34, 13453-13459.
36) "Structure-Activity Relationships for Inhibition of Type 1 and 2 Human 5 - Reductase and Human Adrenal 3-Hydroxy-5-steroid Dehydrogenase/3-Keto-
5-steroid Isomerase by 6-Azaandrost-4-en-3-ones: Optimization of the C17
Substituent", *Frye, S.; Haffner, C.; Maloney, P.; Hiner, R.; Dorsey, Jr., G.; Noe,
R.; Unwalla, R.; Batchelor, K.; Bramson, H. N.; Stuart, J. D.; Schweiker, S.;
Arnold, J.v-.; Bickett, D. M.; Moss, M.; Tian, G.; Lee, F.; Tippin, T.; James, M.;
Grizzle, M.; Long, J.; Croom, D.,J. Med.Chem. 1995, 38, 2621-2627.
37) "6-Azasteroids: Structure-Activity Relationships for Inhibition of Type 1 and 2 Human 5-Reductase and Human Adrenal 3-Hydroxy-5-steroid
Dehydrogenase/3-Keto-5-steroid Isomerase", *Frye, S.; Haffner, C.; Maloney,
P.; Mook, Jr., R.; Dorsey, Jr., G.; Hiner, R.; Cribbs, C.; Wheeler, T.; Ray, J.;
Andrews, R.; Batchelor, K.; Bramson, H. N.; Stuart, J. D.; Schwiker, S.; Arnold,
J.v-; Croom, S.; Bickett, D. M.; Moss, M.; Tian, G.; Unwalla, R.; Lee, F.; Tippin,
T.; James, M.; Grizzle, M.; Long, J.; Schuster, S., J. Med.Chem. 1994, 37, 2352-
2360.
38) "17-(N-tert-Butylcarbamoyl)-4-aza-5-adrostan-1-en-3-one Is an Active Site- Directed Slow Time-Dependent Inhibitor of Human Steroid 5-Reductase 1", *Tian, G.; Stuart, J. D.; Moss, M.; Dominico, P.; Bramson, H. N.; Patel, I.;
Kadwell, S.; Overton, L.; Kost, T.; Mook, Jr., R.; Frye, S.; Batchelor, K.;
Wiseman, J., Biochemistry, 1994, 33, 2291-2296.
39) "6-Azasteroids: Potent Dual Inhibitors of Human Type 1 and 2 Steroid 5Reductase", *Frye, S.; Haffner, C.; Maloney, P.; Mook, Jr., R.; Dorsey, Jr., G.;
Hiner, R.; Batchelor, K.; Bramson, H. N.; Stuart, J. D.; Schweiker, S.; Arnold, J.v-;
Bickett, D. M.; Moss, M.; Tian, G.; Unwalla, R.; Lee, F.; Tippin, T.; James, M.;
Grizzle, M.; Long, J.; Schuster, S., J. Med. Chem. 1993, 36, 4313-4315.
40) "Synthesis of 2-Aminobenzophenones via Rapid Halogen-Lithium Exchange in the Presence of a 2-Amino-N-methoxy-N-methylbenzamide", *Frye, S.; Johnson, M.;
Valvano, N., J. Org. Chem. 1991, 56, 3750-3752.

Resulting from research as adjunct faculty at UNC

41) "Chelates as Intermediates in Nucleophilic Additions to Alkoxy Ketones According to Cram's Rule (Cyclic Model)", Chen, X.; Hortelano, E.; *Eliel, E.;
*Frye, S., J. Am. Chem. Soc. 1992,114, 1778-1784.
42) "Asymmetric Synthesis and Cram's (Chelate) Rule", *Eliel, E.; Frye, S.; Hortelano, E.; Chen, X.; Bai, X., Pure & Appl. Chem. 1991, 63, 1591-1598.
43) "Are Chelates Truly Intermediates in Cram's Chelate Rule?", Chen, X.; Hortelano, E.; *Eliel, E.; *Frye, S., J. Am. Chem. Soc. 1990,112, 6130-6131.
Resulting from PhD research
44) "Asymmetric Synthesis Based On 1,3-Oxathianes-4. Mechanism of Asymmetric Induction in the Reactions of Oxathianyl Ketones", Frye, S.; *Eliel, E., J. Am.
Chem. Soc.
1988,110, 484-489.
45) "Chiral 1,3-Oxathiane From (+)-Pulegone [Hexahydro-4,4,7-trimethyl-4H-1,3- benzoxathiin]", *Eliel, E.; Lynch, J.; Kume, F.; Frye, S., Org. Syntheses 1987, 65,
215-223.
46) "Rapid Injection Nuclear Magnetic Resonance Investigation of the Reactivity of - and -Alkoxyketones with Dimethylmagnesium. Kinetic Evidence for
Chelation", *Frye, S.; Eliel, E.; Cloux, R., J. Am. Chem. Soc. 1987,109, 1862-
1863.
47) "Prevention of Chelation by an Oxygen Function Through Protection with a Triisopropylsilyl Group", Frye, S.; *Eliel, E., Tetrahedron Lett. 1986, 27, 3223-
3226.
48) "Nonenzymatic Asymmetric Synthesis of (R)-(-)- and (S)-(+)-Mevalolactone in High Enantiomeric Purity", Frye, S.; *Eliel, E., J. Org. Chem. 1985, 50, 3402-
3404.
49) "Asymmetric Synthesis of (R)- and (S)-Citramalate in High Enantiomeric Purity", Frye, S.; *Eliel, E., Tetrahedron Lett. 1985, 26, 3907-3910.
Issued patents and recent filings

50) "Pyrazolopyrimidine Compounds for the Treatment of Cancer", Wang, X.; Liu, J.; Yang, C.; Kireev, D., Frye, S., PCT Int. Appl. 2011, WO 2011/146313.
51) "Functionally Selective Ligands of Dopamine D2 Receptors", Jin, J.; Roth, B.; Frye, S., US61/360,951, provisionally filed 7/2/2010. 52) "Compounds and Methods for Treating Pain and Other Conditions", Zylka, M.; Jin, J.; Frye, S., US61/277,136, provisionally filed 9/21/2009. 53) "Preparation of benzo[f]isoindoles as EP4 receptor ligands", Giblin, G.; Frye, S.; Roomans, S., PCT Int. Appl. 2002, 33 pp.
54) "Preparation of 4-azaandrostanones as 5-reductase inhibitors", Batchelor, K.; Frye, S., US 5998427. 55) "Preparation of azaandrostenones for the treatment of androgen responsive diseases", Batchelor, K.; Frye, S., US 5977126. 56) "Preparation of oxindoles as protein tyrosine kinase and protein serine/threonine kinase inhibitors", Davis, S.; Dickerson, S.; Frye, S.; Harris, P.; Hunter III, R.; Kuyper, L.; Lackey, K.; Luzzio, M.; Veal, J.; Walker, D., WO 98-EP5559 19980903. 57) "Inhibitors of 5-Alpha-Testosterone Reductase", Andrews, R.; Cribbs, C.; Frye, S.; Haffner, C.; Maloney, P., US 5543406. 58) "Androstenones", Batchelor, K.; Frye, S., WO 95/07926. Issued in the US: 59) "Androstenone Derivative", Batchelor, K.; Frye, S., WO 95/07927. Issued in the 60) "17--Acyl-6-Azaandrost-4,6-Diazo-4-ene-3-ones", Frye, S.; Middlemiss, D.; Fang, F., US 5457098. 61) "Heterocyclic Inhibitors of 5-Alpha-Testosterone Reductase", Frye, S.; Middlemiss, D.; Fang, R., US 5302589. 62) "Substituted 6-Azaandrostenones", Andrews, R.; Cribbs, C.; Frye, S.; Haffner, C.; Maloney, P., WO 94/14833. 63) "Inhibitors of 5-Alpha-Testosterone Reductase", Frye, S.; Cribbs, C.; Haffner, C.; Maloney, P.; Andrews, R., WO 93/13124. 64) "Cobalt Porphyrins", Johnson, M.; Frye, S., US 5192757. 65) "Cobalt Porphyrin Pharmaceutical Compositions", Johnson, M.; Frye, S., US 66) "Synthesis of 2-Aminobenzophenones", Johnson, M.; Frye, S., US 5136085. 67) "Synthesis of 2-Aminobenzophenones", Johnson, M.; Frye, S., US 5053543. Selected Presentations & Meetings

1) Keynote Speaker "Chemical Biology of Methyl-Lysine", SBNet 2012, Swedish Structural Biology Network, Tällberg, June 15th, 2012. 2) Werblow Lecture "Chemical Biology of Methyl-Lysine", Weill Cornell Medical College, May 22nd, 2012. 3) Invited Speaker "Chemical Biology of Methyl-Lysine", Transcription and Cancer Meeting, Banbury Center, Cold Spring Harbor, April 24th, 2012. 4) Invited Speaker "Chemical Biology of Methyl-Lysine", Drug Development and Pharmacogenomics Academy, Emory University, April 4th, 2012. 5) Co-chair "Addressing the Challenges of Drug Discovery – Novel Targets, New Chemical Space and Emerging Approaches", Keystone Symposia, Tahoe City, March 19-23, 2012. 6) Invited Speaker "Chemical Biology of Methyl-Lysine", John Hopkins Department of Pharmacology, Baltimore, October 20th, 2011. 7) Invited Speaker "Building Academic Drug Discovery Centers", Drug Discovery in Academia, Baltimore, October 18th, 2011. 8) Invited Speaker "The Role of Academic Drug Discovery and Chemical Biology of Chromatin Regulation", Frontiers in Chemical Biology and Drug Discovery, Stony Brook SUNY, October 14th, 2011. 9) Invited Speaker "Chemical Biology of Methyl-Lysine", Vertex, Cambridge, October 10) Invited Speaker "Chemical Biology of Methyl-Lysine", Eli Lilly, Indianapolis, September 27th, 2011. 11) Invited Speaker "Academic Drug Discovery: US Perspective and Examples", NCI Translational Science Meeting, Washington DC, July 29th, 2011. 12) Invited Speaker "Kinase Chemical Probes – Why?" Structural Genomics Consortium Annual Retreat, Barbados, May 4th, 2011. 13) Invited Speaker "Promoting Illiteracy in Epigenetics: Antagonists of the Readers and Writers of the Histone Code", Department Cellular and Molecular Pharmacology, UCSF, April 18th, 2011. 14) Invited Speaker "Promoting Illiteracy in Epigenetics: Antagonists of the Readers and Writers of the Histone Code", Genetech, San Francisco, April 19th, 2011. 15) Invited Speaker "Promoting Illiteracy in Epigenetics: Antagonists of the Readers and Writers of the Histone Code", Division of Chemical Biology, Walter & Eliza Hall Institute of Medical Research, Melbourne, Australia, March 4th, 2011. 16) Invited Speaker "Promoting Illiteracy in Epigenetics: Antagonists of the Readers and Writers of the Histone Code", Structural Biology and Drug Discovery Conference, Cancun, December 2010. 17) Invited Speaker "Chemical Biology Consortium – Overview of Funded Projects", American Association of Cancer Institutes, Chicago, October 2010. 18) Invited Speaker & Session Chair, "Why Academic Drug Discovery Makes Sense", SBS Symposium, Research Triangle Park, October 2010. 19) Invited Speaker, "Promoting Illiteracy in Epigenetics: Antagonists of the Readers of the Epigenetic Code", Jilin University Chemical Biology and Drug Discovery Symposium, Changchun China, May, 2010. 20) Keynote Speaker, "Chemical Biology of Epigenetics: Antagonists of the Readers and Writers of the Histone Code", Alabama Drug Discovery Alliance Symposium, Birmingham, May 2010. 21) Invited Speaker, "Promoting Illiteracy in Epigenetics: Antagonists of the Readers and Writers of the Epigenetic Code", American Chemical Society National Meeting, San Francisco, March 2010. 22) Invited Speaker, "Promoting Illiteracy in Epigenetics: Antagonists of the Readers and Writers of the Epigenetic Code", Epigenetic Mechanisms in Health and Disease, Toronto, Canada, October 2009. 23) Invited Speaker, "Target Identification and Validation in the Context of Gene Families, a Chemical Biology Perspective" Medicinal Biochemistry Symposium, UNC-Greensboro, April 2009. 24) Invited Speaker, "Target Identification and Validation in the Context of Gene Families, a Chemical Biology Perspective", Karolinska Structural Genomics Consortium Symposium, Stockholm, Sweden, March 2009. 25) Invited Speaker, "Drug Discovery and Intellectual Property Strategy in Academia", Society for Biomolecular Screening, Valley Forge, PA, October 2008. 26) Invited Speaker, "Translational Medicine: Role of Academic Drug Discovery", BioPharm America, Atlanta, GA, September 2008. 27) Invited Speaker, "Mechanistic Understanding in Organic Chemistry and Drug Discovery", Reaction Mechanisms Conference, Chapel Hill, NC, June 2008. 28) Chair: 2008 Chapel Hill Drug Conference, Chapel Hill, NC, May 16-17. 29) Invited Speaker: "Target Validation and Drug Discovery in the Context of Gene Families", European Symposium on Bio-Organic Chemistry, Gregynog, Wales, May 2007. 30) Invited Speaker: "Target Identification and Validation in the Context of Gene Families", Therapeutic Applications of Computational Chemistry and Biology, Wellcome Trust Conference Center, Hinxton, UK, March 2007. 31) Invited Speaker: "Target-Class Focused High Throughput Chemistry", Combinatorial Chemistry Gordon Research Conference, Oxford, UK, August 2006. 32) "Structure Activity Relationship And Homology (SARAH): A Genomic Approach to Protein Kinase Drug Discovery", American Association of Cancer Research, New Orleans LA, March 2001. 33) Co-chair: 2000 Bioorganic Gordon Research Conference, Proctor Academy, Andover NH, June 18-23. 34) Invited Speaker: "Kinase Systems Based Research: Target Class Science for Drug Discovery", University of California at San Francisco & Berkeley, March, 2000. 35) Invited Speaker: "Discovery and Development of GG745, A Potent Inhibitor of Both Isozymes of 5-Reductase", Symposium on Urogenital Disease, American Chemical Society National Meeting, Boston, MA, August, 1998 36) Invited Speaker: "Characterization of a Microsomal Metalloendopeptidase That Processes Tumor Necrosis Factor", Gordon Research Conference: Bioorganic Chemistry, Plymouth State College, NH 1996. 37) "6-Azasteroids: Potent Dual Inhibitors of Human Type 1 and 2 Steroid 5- Reductase", American Chemical Society National Meeting, San Diego, CA, March, 1994. 38) Invited Speaker: "Are Chelates Truly Intermediates in Cram's Chelate Rule?", Gordon Research Conference: Stereochemistry, Salve Regina College, Newport, RI, 1992. 39) "One-Pot Halogen-Lithium Exchange, N-Methoxy-N-Methylamide Route to 2- Aminobenzophenones", Poster Sesson, French-American Chemical Society, Captiva Island, Florida, 1991. 40) "Rapid Injection Nuclear Magnetic Resonance Investigation of the Reactivity of - and -Alkoxyketones with Dimethylmagnesium. Kinetic Evidence for Chelation", American Chemical Society National Meeting, Denver, Colorado, 1987. 41) "Prevention of Chelation by an Oxygen Function Through Protection with a Triisopropylsilyl Group", American Chemical Society Southeastern Regional Meeting, Louisville, Kentucky, 1986. 42) "Asymmetric Synthesis of (R)- and (S)-Mevalolactone and (R)- and (S)- Citramalic Acid in High Enantiomeric Purity", American Chemical Society National Meeting, Chicago, Illinois, 1985. RESEARCH SUPPORT

ACTIVE
1R01 GM100919-01(Frye)
1.8 calendar months Discovery of Chemical Probes for Methyllysine Readers
We propose to discover antagonists of the malignant brain tumor (MBT) repeat -
a structural domain of ca. 100 amino acids which occurs in 9 human proteins
which recognize mono- and dimethyllysine modifications of histones. There are
no known high-quality chemical probes targeting MBT domains. The overarching
objectives of this program are to develop pharmacological probes of methyl-
lysine binding domains to pioneer both the validation of specific domains and the
assay framework in which issues of selectivity and mechanism of action can be
assessed.
1 R01 NS067688-01 (Zylka)
0.24 calendar months TDC to CICBDD $825,000; 9/1/2010-8/31/2011 $165,500 Harnessing Ectonucleotidases to Treat Chronic Pain
In this application we propose to discover and develop novel pro-drugs targeting
prostatic acid phosphatase for treating chronic pain.

BOA 29XS126
(Frye)
varies by task order (see below) NCI/SAIC-Frederick, Inc. North Carolina Comprehensive Chemical Biology Screening Center
This Basic Ordering Agreement was issued by the NCI to members of the
Chemical Biology Consortium to facilitate the discovery and development of new
reagents to treat cancer. Dr. Frye is the Director of the NC Comprehensive
Chemical Biology Screening Center which includes the University of North
Carolina at Chapel Hill, The Hamner Institutes, and North Carolina Central
University. The amount of support will vary depending on the requirements of
the task orders issued.
BOA 29XS126 (Frye, Lead PI)
1.8 calendar months NCI/SAIC-Frederick, Inc. $543,002 (Task Order 09) Target Validation, Assay Development and Hit Discovery for IDH1-Based
Approaches targeting Glioblastoma
. This contract award funds specific tasks and
milestones to (1) purify mutant IDH1 proteins and develop an in vitro enzymatic
assay to detect production of α-KG and 2-HG; (2) optimize high-throughput assay
for discovery of inhibitors of mutant IDH1 2-HG production; and (3) tractable hit
discovery as defined in the Statement of Work.
BOA 29XS126 (Frye, Lead PI)
1.8 calendar months NCI/SAIC-Frederick, Inc. $1,661,940 TDC 8/13/11-8/12/12 (Task Order 07)
Developing Small Molecule Mer Inhibitor Candidates for Novel Treatment of
Acute Lymphoblastic Leukemia.
This contract funds specific tasks and
milestones to develop Mer-selective small molecules as drug candidates to treat
ALL and as tool compounds to uncover the mechanism whereby Mer activation
sustains the survival and perhaps contributes to the maturity and niche
adaptation of lymphoid malignancies and selected carcinomas that overexpress
Mer as defined in the Statement of Work.
BOA 29XS126 (Frye)
1.8 calendar months NCI/SAIC-Frederick, Inc. $323,962 (Task Order 08) To provide 1.5 FTE staff positions (project manager and administrative officer) dedicated to the support and coordination of activities related to the North Carolina Comprehensive Chemical Biology Screening Center that are not related to specific projects in order to meet the operational needs of the NCI's Chemical Biology Consortium (CBC) and its project activities. In March 2010 SAIC expanded the scope to include 15% time and effort of the PI that is dedicated to supervision of support staff awarded under Task Order 08, direction of the conduct of CBC-related activities that lie outside the scope of awarded task orders, and oversight of the group of task orders awarded to the North Carolina Comprehensive Chemical Biology Screening Center.
3 U19 MH082441-04S1 (Roth; Project PI – Jin) 1/19/09-4/30/12 0.24 calendar
months
NIH
TDC to CICBDD $679,000; 5/1/10-4/30/11 $224,297 Functional Selectivity: A Novel Approach for CNS Drug Discovery
The overall objectives of this project are to create novel dopamine D2 ligands
with unprecedented patterns of functional selectivity for elucidating the key signal
transduction pathways essential for antipsychotic efficacy, and to discover novel,
functionally selective antipsychotic drug candidates that are safer and more
effective than existing antipsychotics.
1 R03 DA030553-01 (Janzen)
0.12 calendar months TDC $50,000; 5/1/10-4/30/11 $20,000 High-throughput Screening for the Discovery of Novel Scaffolds that Antagonize
Methylated Histone Recognition
The main goal of this proposal is to develop small molecule probes that inhibit
the binding of the L3BMBTL1 methyl lysine binding protein to histone tails by
running a high throughput screening assay at the MLPCN.
COMPLETED
1 RC1 GM090732-01 (Frye)
3 calendar months NIH Challenge Grant TDC $591,758; 9/1/10-8/31/11 $298,383 Discovery of Small Molecule MBT Domain Antagonists
We propose to develop potent antagonists of methyl-lysine recognition by human
and Drosophila MBT domain containing proteins in order to permit exploration of
the biological consequences of blocking this recognition in cell based and in vivo
models with relevance to normal and disease biology. Specifically, we propose
to 1) develop biological assays for human and Drosophila MBT containing
proteins; 2) use focused and diversity based screening, virtual screening, and
structure-based design to identify potential antagonists of methyl-lysine
recognition; and 3) optimize hits via iterative design, synthesis, and biological
assessment.

HRSA-09-163
(Frye)
09/01/09-6/30/2010 Equipment Only $163,330 Automated Compound Storage System for the Center for Integrative Chemical
Biology and Drug Discovery at the University of North Carolina at Chapel Hill
The award provides partial funding for the acquisition of an automated compound
storage and retrieval system for storing liquid aliquots of the Center's collection of
small molecules for use in drug discovery and as tool compounds. Samples will
be stored to facilitate cherry-picking compounds or sets of compounds and
arraying them in user specific formats. No salary support is included.
BOA 29XS126 (Frye, Lead PI)
0.2 calendar months NCI/SAIC-Frederick, Inc. $31,881 (Task Order 01)
For participation in a network collaborative effort to develop a shared curation filter for a
pooled compound file library consisting of the curated libraries of each CBC member
organization using standard criteria agreed upon by all members.
PROFESSIONAL SERVICE

External reviewer for the Higuchi Biosciences Center at U. Kansas, January 2012.
Advisory Committee to the Canadian Cancer Stem Cell Consortium (CSCC), 2011.
Cooperative Research Center for Cancer Therapeutics, Australia, Third Year
Review Panel Member, March 2011
Collaborative Ependymoma Research Network (CERN), Member, 2010-present
St. Jude Children's Hospital, Chemical Biology and Therapeutics Review Group,
August, 2010
University of Dundee Division of Biological Chemistry and Drug Discovery,
Quinquennial Review Board member, September, 2009
Moffitt Cancer Center P01 External Advisory Board member, January, 2009
National Academy of Sciences invited participant: "The Chemistry Platform for
Pharmaceuticals: A scoping meeting", August, 2008
Harvard Medical School Therapeutics Strategy Retreat invited speaker, October
2008
North Carolina Drug Discovery Center of Innovation Steering Group and
Scientific Advisory Board, January 2008 - present
Scientific Advisory Committee member of the Structural Genomics Consortium,
August 2007 – present
External Advisory Board Member to UNC Department of Chemistry, 2003 – 2007
Physical and Mathematical Sciences Advisory Board Member, NCSU, 2003 –
present

Peer reviewer for funding agencies

NIH Molecular Libraries Probe Network, Member of Probe Report Review Board,
2010-2011

Wellcome Trust, Peer Reviewer, 2010-present
BBSRC UK Research Council, Peer Reviewer, 2011
Research Corporation for Science Advancement, 2009-2010
UNC Gillings Innovation Lab Proposals, Reviewer, 2010
Cancer Research UK, Program Reviewer, 2010
North Carolina Biotechnology Center, Education Enhancement Grant Reviewer,
2009
Peer reviewer for scholarly journals

ACS Medicinal Chemistry Letters
Biochemistry
Bioorganic and Medicinal Chemistry
Drug Discovery Today
Cell
Chemistry and Biology (editorial board member)
Journal of Medicinal Chemistry
Nature
Nature Chemical Biology
Nature Biotechnology
Medicinal Chemistry Communications
Pharmaceutical Research
Proceedings of the National Academy of Sciences
Tetrahedron Letters
Service to UNC-CH
Member of the Chancellor's Innovation Circle, Chair: Judith Cole, 2009-present
Member of Biochemistry and Biophysics Faculty Search Committee, Chair: Leslie
Parise, 2007-2010
Member of the University Cancer Research Fund Therapeutics Theme Team,
Chair: Ned Sharpless, 2009-present
Service to the School of Pharmacy
Member of Senior Faculty Search Committee, Chair: Hal Kohn, 2010-11
Chair of Faculty Search Committee for Carolina Partnership CICBDD
Recruitment, 2009
Seminar speakers hosted: Kevan Shokat (UCSF), Aled Edwards (U. Toronto),
Cheryl Arrowsmith (U. Toronto), Ben Cravatt (Scripps)
Member of Search Committee for SOP Human Resources Staff Hire, 2008

Organized and chaired the 2008 Chapel Hill Drug Conference
PhD Thesis Committees
Tim O'Leary (Jian Liu, Medicinal Chemistry)
Man Lou (Alex Tropsha, Medicinal Chemistry)
Jon Edwards (Matt Redinbo, Chemistry)
Sherket Peterson (Jian Liu, Medicinal Chemistry)
Brett Wallace (Matt Redinbo, Chemistry)
Marty Whittle (Gary Johnson, Pharmacology)
Morgan Chapman (Scott Singleton, Medicinal Chemistry)
Amber King (Hal Kohn, Medicinal Chemistry)
Pierre Morieux (Hal Kohn, Medicinal Chemistry)
Jui-Hua Hsien (Alex Tropsha, Medicinal Chemistry)
Venita Gresham (Howard McLeod, Pharmacotherapy and Experimental
Therapeutics)
David Grawoig (Weeks, Chemistry)
Wei Sun (Zhang, Medicinal Chemistry)
Nate Oien (Lawrence, Medicinal Chemistry)

Source: https://unclineberger.org/people/stephen-v-frye/@@download/cv_biosketch/Frye%20Stephen_CV_29June2012.pdf

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