Paul Brennan
Structural Genomics Consortium
Target Discovery Institute
Nuffield Department of Medicine
University of Oxford
Old Road Campus
Oxford, OX3 7DQ, UK
e-mail: paul.brennan@sgc.ox.ac.uk
US Citizen with Indefinite Leave to Remain in the UK
Summary
I am an industry trained, innovative and successful medicinal chemistry with diverse experience,
a history of clinical candidate delivery and a strong background in synthetic organic and
medicinal chemistry. I have led and delivered advanced compounds in projects targeting major
disease targets: kinase inhibitors, GPCR agonists and antagonists, metabolic enzymes, ion
channels and chromatin modifiers.
As the principal investigator of medicinal chemistry at the Structural Genomics Consortium in
Oxford University, I lead the chemistry team dedicated to designing and synthesizing openaccess small molecule probes for epigenetic proteins in order to elucidate the mechanism of
epigenetic regulation, one of the most exciting new areas of human biology.
Experience
Present
Structural Genomics Consortium, University of Oxford.
Principal Investigator in Medicinal Chemistry leading a group of doctoral and postdoctoral researchers.
Research projects: Small molecule epigenetic probes for bromodomains, tudor
domains and histone demethylases.
20052011
Pfizer, Sandwich, UK. Senior Principal Scientist and chemistry team leader in
Urology, Allergy and Respiratory, Epigenetics.
Research projects:
 CNS GPCR agonists and antagonists for incontinence and obesity
 Peripheral GPCR antagonists for respiratory disease
 Ion channel antagonists for pain
 Enzyme inhibitors for respiratory disease
2003-2005
Amgen, Thousand Oaks, California.
Research Scientist and chemistry team leader;
Research projects:
•PLK Serine/threonine kinase inhibitor for oncology
•Tyrosine kinase inhibitor for oncology
2000-2003
University of Cambridge, Department of Chemistry
Post-doctoral Researcher and chemistry team leader
Advisor: Professor Steven V. Ley
Research projects:
The Total Synthesis of Rapamycin
Synthesis of Oligosaccharides Using Clean Chemistry
Suzuki Cross Coupling with Pd-containing Perovskites.
1998
Pharmacopeia Inc. Princeton, New Jersey. Summer Intern.
• Multi-step organic synthesis
• Solid-Phase combinatorial chemistry
1989-1991
Genta Incorporated (now Promega Corporation) San Luis Obispo, California.
Research Associate.
• Synthesis and HPLC purification of anti-sense oligonucleotides
• Synthesis of modified nucleosides
Education
1995-2000
University of California, Berkeley
PhD in Organic Chemistry; awarded April 2000
Advisor: Professor Paul A. Bartlett, Ph.D.
Thesis title: I. Phosphinate Inhibitors of Peptidoglycan Biosynthesis.
II. Development of a New Ring System for Combinatorial Chemistry
1991-1995
University of California, Davis
Bachelor of Science in Chemistry, with high honors; awarded June 1995. Awarded
Most Outstanding Student in Organic Chemistry.
Senior thesis title: Site Isolation Studies on Solid Support
Advisor: Professor Mark J. Kurth, PhD
Professional Associations
Present
Medical Research Council
Development Pathway Funding Scheme review panel.
Present
3D-Fragment Library Consortium
Steering Committee.
References
Chas Bountra, PhD
Mark Bunnage, PhD
Chief Scientist
Structural Genomics Consortium
University of Oxford, UK
VP, Head of Chemistry
Biotherapeutics Research
Pfizer, Cambridge, MA
e-mail:
chas.bountra@sgc.ox.ac.uk
e-mail:
mark.bunnage@pfizer.com
Steven V. Ley,
PhD, FRS, CBE
Professor of Chemistry
University of Cambridge,
UK
e-mail:
svl1000@cam.ac.uk
Paul A. Bartlett, PhD
Professor of Chemistry
College of Chemistry
University of California,
Berkeley, USA
e-mail:
paul@fire.cchem.berkeley.ed
u
Publications and Patents
(1)
Yue, W. W.; Froese, D. S.; Brennan, P. E.: The Role of Protein Structural Analysis in the Next Generation Sequencing Era. In
Top Curr Chem, 2012. Top Curr Chem, Springer Berlin / Heidelberg, 2012, pp 1-32.
(2)
Rose, N. R.; Woon, E. C. Y.; Tumber, A.; Walport, L. J.; Chowdhury, R.; Li, X. S.; King, O. N. F.; Lejeune, C.; Ng, S. S.; Krojer,
T.; Chan, M. C.; Rydzik, A. M.; Hopkinson, R. J.; Che, K.; Daniel, M.; Strain-Damerell, C.; Gileadi, C.; Kochan, G.; Leung, I. K. H.;
Dunford, J. E.; Yeoh, K. K.; Ratcliffe, P. J.; Burgess-Brown, N.; von Delft, F.; Muller, S.; Marsden, B.; Brennan, P. E.; McDonough, M.
A.; Oppermann, U. C. T.; Klose, R.; Schofield, C. J.; Kawamura, A.: The Plant Growth Regulator Daminozide is a Selective Inhibitor of
the Human KDM2/7 Histone Demethylases. Journal of Medicinal Chemistry 2012; [online] DOI 10.1021/jm300677j.
(3)
Brennan, P.; Filippakopoulos, P.; Knapp, S.: The therapeutic potential of acetyl-lysine and methyl-lysine effector domains.
Drug Discovery Today: Therapeutic Strategies 2012. [online] DOI 10.1016/j.ddstr.2012.04.001.
(4)
Ho, D. K. H.; Chan, L.; Hooper, A.; Brennan, P. E.: A general and mild two-step procedure for the synthesis of aryl and
heteroaryl sulfonamides from the corresponding iodides. Tetrahedron Lett. 2011, 52, 820-823.
(5)
Ball, J. C.; Brennan, P.; Elsunaki, T. M.; Jaunet, A.; Jones, S.: A tandem asymmetric synthesis approach for the efficient
preparation of enantiomerically pure 9-(hydroxyethyl) anthracene. Tetrahedron: Asymmetry 2011, 22, 253-255.
(6)
Andrews, M. D.; Fish, P. V.; Blagg, J.; Brabham, T. K.; Brennan, P. E.; Bridgeland, A.; Brown, A. D.; Bungay, P. J.; Conlon, K.
M.; Edmunds, N. J.; af, F. K.; Gibbons, C. P.; Green, M. P.; Hanton, G.; Holbrook, M.; Jessiman, A. S.; McIntosh, K.; McMurray, G.;
Nichols, C. L.; Root, J. A.; Storer, R. I.; Sutton, M. R.; Ward, R. V.; Westbrook, D.; Whitlock, G. A.: Pyrimido[4,5-d]azepines as potent
and selective 5-HT2C receptor agonists: design, synthesis, and evaluation of PF-3246799 as a treatment for urinary incontinence.
Bioorg Med Chem Lett 2011, 21, 2715-20.
(7)
Whitlock, G. A.; Brennan, P. E.; Roberts, L. R.; Stobie, A.: Potent and selective α1A adrenoceptor partial agonists-Novel
imidazole frameworks. Bioorg. Med. Chem. Lett. 2009, 19, 3118-3121.
(8)
Ley, S. V.; Tackett, M. N.; Maddess, M. L.; Anderson, J. C.; Brennan, P. E.; Cappi, M. W.; Heer, J. P.; Helgen, C.; Kori, M.;
Kouklovsky, C.; Marsden, S. P.; Norman, J.; Osborn, D. P.; Palomero, M. A.; Pavey, J. B. J.; Pinel, C.; Robinson, L. A.; Schnaubelt, J.;
Scott, J. S.; Spilling, C. D.; Watanabe, H.; Wesson, K. E.; Willis, M. C.: Total synthesis of rapamycin. Chem.--Eur. J. 2009, 15, 28742914.
(9)
Brennan, P. E.; Whitlock, G. A.; Ho, D. K. H.; Conlon, K.; McMurray, G.: Discovery of a novel azepine series of potent and
selective 5-HT2C agonists as potential treatments for urinary incontinence. Bioorg. Med. Chem. Lett. 2009, 19, 4999-5003.
(10)
Andrews, M. D.; Blagg, J.; Brennan, P. E.; Fish, P. V.; Roberts, L. R.; Storer, R. I.; Whitlock, G. A.: Preparation of pyrimido[4,5d]azepine derivatives as 5-HT2C agonists. Pfizer Limited, UK . 2008; pp180pp.
(11)
Maddess, M. L.; Tackett, M. N.; Watanabe, H.; Brennan, P. E.; Spilling, C. D.; Scott, J. S.; Osborn, D. P.; Ley, S. V.: Total
synthesis of rapamycin. Angew. Chem., Int. Ed. 2007, 46, 591-597.
(12)
Smith, A. L.; Brennan, P. E.; Demorin, F. F.; Liu, G.; Paras, N. A.; Retz, D. M.: Aminopyrimidine compounds as polo-like
kinase 1 inhibitors and their preparation, pharmaceutical compositions and use for treatment of cancer. Amgen, Inc., USA . 2006; pp
151 pp.
(13)
Smith, M. D.; Stepan, A. F.; Ramarao, C.; Brennan, P. E.; Ley, S. V.: Palladium-containing perovskites: recoverable and
reuseable catalysts for Suzuki couplings. Chem. Commun. (Cambridge, U. K.) 2003, 2652-2653.
(14)
MacCoss, R. N.; Brennan, P. E.; Ley, S. V.: Synthesis of carbohydrate derivatives using solid-phase work-up and scavenging
techniques. Org. Biomol. Chem. 2003, 1, 2029-2031.
(15)
Spaller, M. R.; Thielemann, W. T.; Brennan, P. E.; Bartlett, P. A.: Combinatorial Synthetic Design. Solution and PolymerSupported Synthesis of Heterocycles via Intramolecular Aza Diels-Alder and Imino Alcohol Cyclizations. J. Comb. Chem. 2002, 4, 516522.
(16)
Brennan, P. E.; Ley, S. V.: New catalysts for olefin metathesis. Chemtracts 2001, 14, 88-93.
(17)
Dolle, R. E.; Barden, M. C.; Brennan, P. E.; Ahmed, G.; Tran, V.; Ho, D. M.: Application of the intramolecular azomethine imine
cycloaddition to the construction of a novel, orthogonally protected spirodiamino acid scaffold. Tetrahedron Lett. 1999, 40, 2907-2908.