Paul Brennan
Structural Genomics Consortium
Target Discovery Institute
Nuffield Department of Medicine
University of Oxford
Old Road Campus
Oxford, OX3 7DQ, UK
e-mail:
US Citizen with IndefiniteLeave to Remain in the UK
Summary
I am an industry trained,innovative and successful medicinal chemistrywith 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 open-access 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
Structural Genomics Consortium, University of Oxford.
Principal Investigator in Medicinal Chemistryleading a group of doctoral and post-doctoral researchers.
Research projects: Small molecule epigenetic probes for bromodomains, tudor domains and histone demethylases.
Pfizer, Sandwich, UK. Senior Principal Scientistand 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
Amgen, Thousand Oaks, California.
Research Scientist and chemistry team leader;
Research projects:
•PLK Serine/threonine kinase inhibitor for oncology
•Tyrosine kinase inhibitor for oncology
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.
Pharmacopeia Inc.Princeton, New Jersey. Summer Intern.
• Multi-step organic synthesis
• Solid-Phase combinatorial chemistry
Genta Incorporated (now Promega Corporation) San Luis Obispo, California. Research Associate.
• Synthesis and HPLC purification of anti-sense oligonucleotides
• Synthesis of modified nucleosides
Education
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
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
Medical Research Council
Development Pathway Funding Scheme review panel.
3D-Fragment Library Consortium
Steering Committee.
References
Chas Bountra, PhD / Mark Bunnage, PhD / Steven V. Ley,PhD, FRS, CBE / Paul A. Bartlett, PhD
Chief Scientist / VP, Head of Chemistry / Professor of Chemistry
Structural Genomics Consortium / Biotherapeutics Research / Professor of Chemistry / College of Chemistry
University of Oxford, UK / Pfizer, Cambridge, MA / University of Cambridge, UK / University of California, Berkeley, USA
e-mail: / e-mail: / e-mail:
/ e-mail:
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 CurrChem, 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 Chemistry2012; [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 Strategies2012. [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: Asymmetry2011, 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 Lett2011, 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, 2874-2914.
(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[4,5-d]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 Polymer-Supported Synthesis of Heterocycles via Intramolecular Aza Diels-Alder and Imino Alcohol Cyclizations. J. Comb. Chem.2002, 4, 516-522.
(16)Brennan, P. E.; Ley, S. V.: New catalysts for olefin metathesis. Chemtracts2001, 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.