Paul Brennan

Principal Investigator / Associate Professor

University of Oxford
+44 (0)1865 612932

Paul Brennan received his PhD in organic chemistry from the University of California, Berkeley under the mentorship of Paul Bartlett working on synthetic methodology for combinatorial chemistry and synthesizing inhibitors for new anti-bacterial targets.  Following three years of post-doctoral research with Steve Ley in Cambridge University on the total synthesis of rapamycin, Paul returned to California to take a position at Amgen.  His research was focussed on designing and synthesizing kinase inhibitors for oncology.  After two years at Amgen, Paul accepted a position as Medicinal Chemistry Design Lead at the Pfizer research labs in Sandwich, UK.  Over the next six years Paul designed and synthesized compounds for most major drug classes: GPCR’s, CNS-targets, ion-channels and metabolic enzymes.  Following the closure of the Pfizer site in Sandwich, Paul joined the SGC as the Principal Investigator for medicinal chemistry to discover chemical probes for epigenetic proteins.

Research Areas

The medicinal chemistry group in Oxford is focussed on the design and synthesis of small molecules as chemical probes for epigenetics proteins. We rely heavily on fragment based drug discovery (FBDD) for hit identification and structure based drug design (SBDD) for lead optimization. We collaborate extensively with medicinal chemists and synthetic chemists. The chemical probes developed in the group will decipher the function of epigenetic proteins in disease and provide starting points for drug discovery. By using epigenetic chemical probes in target discovery, we will dramatically accelerate drug discovery in one of the most promising new areas of biomedical research.

Group Members

  • Andrea Nuzzi
  • Gian Filippo Ruda
  • Katherine England
  • Melissa D'Ascenzio
  • Tamas Szommer
  • Stephen Wren
  • Saleta Vazquez Rodriguez
  • Miranda Wright
  • Moses Moustakim
  • Oakley Cox
  • Finn Wolfreys
  • Philip Gerken
  • Pavel Guzanov
  • Milan Fowkes

Publications

Discovery of a Chemical Tool Inhibitor Targeting the Bromodomains of TRIM24 and BRPF.
Bennett, J; Fedorov, O; Tallant, C; Monteiro, O; Meier, J; Gamble, V; Savitsky, P; Nunez-Alonso, GA; Haendler, B; Rogers, C; Brennan, PE; Müller, S; Knapp, S;
Journal of Medicinal Chemistry. 2016 59:1642-1647. doi:
PMID: 25974391

K2P channel gating mechanisms revealed by structures of TREK-2 and a complex with Prozac.
Dong, YY; Pike, AC; Mackenzie, A; McClenaghan, C; Aryal, P; Dong, L; Quigley, A; Grieben, M; Goubin, S; Mukhopadhyay, S; Ruda, GF; Clausen, MV; Cao, L; Brennan, PE; Burgess-Brown, NA; Sansom, MS; Tucker, SJ; Carpenter, EP;
Science. 2015 347:1256-1259. doi:
PMID: 25766236

Inflammatory Signaling by NOD-RIPK2 Is Inhibited by Clinically Relevant Type II Kinase Inhibitors.
Canning, P; Ruan, Q; Schwerd, T; Hrdinka, M; Maki, JL; Saleh, D; Suebsuwong, C; Ray, S; Brennan, PE; Cuny, GD; Uhlig, HH; Gyrd-Hansen, M; Degterev, A; Bullock, AN;
Chemistry and Biology. 2015 22:1174-1184. doi:
PMID: 26320862

CBP30, a selective CBP/p300 bromodomain inhibitor, suppresses human Th17 responses.
Hammitzsch, A; Tallant, C; Fedorov, O; O'Mahony, A; Brennan, PE; Hay, DA; Martinez, FO; Al-Mossawi, MH; de Wit, J; Vecellio, M; Wells, C; Wordsworth, P; Müller, S; Knapp, S; Bowness, P;
Proceedings of the National Academy of Sciences of USA. 2015 112:10768-10773. doi:
PMID: 26261308

Design and synthesis of potent and selective inhibitors of BRD7 and BRD9 bromodomains
Hay, DA; Rogers, CM; Fedorov, O; Tallant, C; Martin, S; Monteiro, OP; Mueller, S; Knapp, S; Schofield, CJ; Brennan, PE;
MedChemComm. 2015 6:1381-1386. doi: 10.1039/c5md00152h
PMID:

LP99: Discovery and Synthesis of the First Selective BRD7/9 Bromodomain Inhibitor.
Clark, PG; Vieira, LC; Tallant, C; Fedorov, O; Singleton, DC; Rogers, CM; Monteiro, OP; Bennett, JM; Baronio, R; Müller, S; Daniels, DL; Méndez, J; Knapp, S; Brennan, PE; Dixon, DJ;
Angewandte Chemie International Edition. 2015 54:6217-6221. doi:
PMID: 25864491

Optimisation of a triazolopyridine based histone demethylase inhibitor yields a potent and selective KDM2A (FBXL11) inhibitor.
England, KS; Tumber, A; Krojer, T; Scozzafava, G; Ng, SS; Daniel, M; Szykowska, A; Che, K; von Delft, F; Burgess-Brown, NA; Kawamura, A; Schofield, CJ; Brennan, PE;
MedChemComm. 2014 5:1879-1886. doi:
PMID: 26682034

Discovery and optimization of small-molecule ligands for the CBP/p300 bromodomains.
Hay, DA; Fedorov, O; Martin, S; Singleton, DC; Tallant, C; Wells, C; Picaud, S; Philpott, M; Monteiro, OP; Rogers, CM; Conway, SJ; Rooney, TP; Tumber, A; Yapp, C; Filippakopoulos, P; Bunnage, ME; Müller, S; Knapp, S; Schofield, CJ; Brennan, PE;
Journal of the American Chemical Society. 2014 136:9308-9319. doi:
PMID: 24946055

A series of potent CREBBP bromodomain ligands reveals an induced-fit pocket stabilized by a cation-π interaction.
Rooney, TP; Filippakopoulos, P; Fedorov, O; Picaud, S; Cortopassi, WA; Hay, DA; Martin, S; Tumber, A; Rogers, CM; Philpott, M; Wang, M; Thompson, AL; Heightman, TD; Pryde, DC; Cook, A; Paton, RS; Müller, S; Knapp, S; Brennan, PE; Conway, SJ;
Angewandte Chemie International Edition. 2014 53:6126-6130. doi:
PMID: 24821300

Machine-assisted synthesis of modulators of the histone reader BRD9 using flow methods of chemistry and frontal affinity chromatography
Guetzoyan, L; Ingham, RJ; Nikbin, N; Rossignol, J; Wolling, M; Baumert, M; Burgess-Brown, NA; Strain-Damerell, CM; Shrestha, L; Brennan, PE; Fedorov, O; Knapp, S; Ley, SV;
MedChemComm. 2014 5:540-546. doi: 10.1039/c4md00007b
PMID:

[1,2,4]triazolo[4,3-a]phthalazines: inhibitors of diverse bromodomains.
Fedorov, O; Lingard, H; Wells, C; Monteiro, OP; Picaud, S; Keates, T; Yapp, C; Philpott, M; Martin, SJ; Felletar, I; Marsden, BD; Filippakopoulos, P; Müller, S; Knapp, S; Brennan, PE;
Journal of Medicinal Chemistry. 2014 57:462-476. doi:
PMID: 24313754

The role of protein structural analysis in the next generation sequencing era.
Yue, WW; Froese, DS; Brennan, PE;
Topics in Current Chemistry. 2014 336:67-98. doi: 10.1007/128_2012_326
PMID: 22610134

Optimizing in vivo probes for the BET bromodomains
Jennings, LE; Hewings, DS; Humphreys, PG; Brennan, PE; Conway, SJ;
ACS National Meeting Book of Abstracts. 2014 248:-. doi:
PMID:

Optimization of 3,5-dimethylisoxazole derivatives as potent bromodomain ligands.
Hewings, DS; Fedorov, O; Filippakopoulos, P; Martin, S; Picaud, S; Tumber, A; Wells, C; Olcina, MM; Freeman, K; Gill, A; Ritchie, AJ; Sheppard, DW; Russell, AJ; Hammond, EM; Knapp, S; Brennan, PE; Conway, SJ;
Journal of Medicinal Chemistry. 2013 56:3217-3227. doi:
PMID: 23517011

The design and synthesis of 5- and 6-isoxazolylbenzimidazoles as selective inhibitors of the BET bromodomains.
Hay, D; Fedorov, O; Filippakopoulos, P; Martin, S; Philpott, M; Picaud, S; Hewings, DS; Uttakar, S; Heightman, TD; Conway, SJ; Knapp, S; Brennan, PE;
MedChemComm. 2013 4:140-144. doi:
PMID: 26682033

Chemical probes for bromodomains outside the BET family
Brennan, PE; Martin, SJ; Monteiro, O; Fedorov, O; Knapp, S; Hay, D; Wells, C; Filippakopoulos, P; Picaud, S; Muller-Knapp, S; Keates, T; Yapp, C; Philpott, M; Schofield, C; Burgess-Brown, N; Shrestha, L; Strain-Damerell, C;
ACS National Meeting Book of Abstracts. 2013 246:-. doi:
PMID:

Fragment-based hit identification: thinking in 3D
Morley, AD; Pugliese, A; Birchall, K; Bower, J; Brennan, P; Brown, N; Chapman, T; Drysdale, M; Gilbert, IH; Hoelder, S; Jordan, A; Ley, SV; Merritt, A; Miller, D; Swarbrick, ME; Wyatt, PG;
Drug Discovery Today. 2013 18:1221-1227. doi: 10.1016/j.drudis.2013.07.011
PMID: 23906694

RVX-208, an inhibitor of BET transcriptional regulators with selectivity for the second bromodomain.
Picaud, S; Wells, C; Felletar, I; Brotherton, D; Martin, S; Savitsky, P; Diez-Dacal, B; Philpott, M; Bountra, C; Lingard, H; Fedorov, O; Müller, S; Brennan, PE; Knapp, S; Filippakopoulos, P;
Proceedings of the National Academy of Sciences of USA. 2013 110:19754-19759. doi:
PMID: 24248379

5-Carboxy-8-hydroxyquinoline is a broad spectrum 2-oxoglutarate oxygenase inhibitor which causes iron translocation
Hopkinson, RJ; Tumber, A; Yapp, C; Chowdhury, R; Aik, W; Che, KH; Li, XS; Kristensen, JBL; King, ONF; Chan, MC; Yeoh, KK; Choi, H; Walport, LJ; Thinnes, CC; Bush, JT; Lejeune, C; Rydzik, AM; Rose, NR; Bagg, EA; McDonough, MA; Krojer, TJ; Yue, WW; Ng, SS; Olsen, L; Brennan, PE; Oppermann, U; Müller, S; Klose, RJ; Ratcliffe, PJ; Schofield, CJ; Kawamura, A;
Chemical Science. 2013 4:3110-3117. doi: 10.1039/c3sc51122g
PMID: 26682036

PFI-1, a highly selective protein interaction inhibitor, targeting BET Bromodomains.
Picaud, S; Da Costa, D; Thanasopoulou, A; Filippakopoulos, P; Fish, PV; Philpott, M; Fedorov, O; Brennan, P; Bunnage, ME; Owen, DR; Bradner, JE; Taniere, P; O'Sullivan, B; Müller, S; Schwaller, J; Stankovic, T; Knapp, S;
Cancer Research. 2013 73:3336-3346. doi:
PMID: 23576556

The therapeutic potential of acetyl-lysine and methyl-lysine effector domains
Brennan, P; Filippakopoulos, P; Knapp, S;
Drug Discovery Today: Therapeutic Strategies. 2012 9:-. doi: 10.1016/j.ddstr.2012.04.001
PMID:

Identification of a chemical probe for bromo and extra C-terminal bromodomain inhibition through optimization of a fragment-derived hit.
Fish, PV; Filippakopoulos, P; Bish, G; Brennan, PE; Bunnage, ME; Cook, AS; Federov, O; Gerstenberger, BS; Jones, H; Knapp, S; Marsden, B; Nocka, K; Owen, DR; Philpott, M; Picaud, S; Primiano, MJ; Ralph, MJ; Sciammetta, N; Trzupek, JD;
Journal of Medicinal Chemistry. 2012 55:9831-9837. doi:
PMID: 23095041

Progress in the development and application of small molecule inhibitors of bromodomain-acetyl-lysine interactions.
Hewings, DS; Rooney, TP; Jennings, LE; Hay, DA; Schofield, CJ; Brennan, PE; Knapp, S; Conway, SJ;
Journal of Medicinal Chemistry. 2012 55:9393-9413. doi: 10.1021/jm300915b
PMID: 22924434

Plant growth regulator daminozide is a selective inhibitor of human KDM2/7 histone demethylases.
Rose, NR; Woon, EC; Tumber, A; Walport, LJ; Chowdhury, R; Li, XS; King, ON; Lejeune, C; Ng, SS; Krojer, T; Chan, MC; Rydzik, AM; Hopkinson, RJ; Che, KH; Daniel, M; Strain-Damerell, C; Gileadi, C; Kochan, G; Leung, IK; Dunford, J; Yeoh, KK; Ratcliffe, PJ; Burgess-Brown, N; von Delft, F; Muller, S; Marsden, B; Brennan, PE; McDonough, MA; Oppermann, U; Klose, RJ; Schofield, CJ; Kawamura, A;
Journal of Medicinal Chemistry. 2012 55:6639-6643. doi: 10.1021/jm300677j
PMID: 22724510

3,5-Dimethylisoxazoles inhibit the bromodomain-histone protein-protein interaction
Hewings, DS; Wang, M; Philpott, M; Fedorov, O; Uttarkar, S; Filippakopoulos, P; Picaud, S; Vuppusetty, C; Marsden, B; Heightman, TD; Knapp, S; Brennan, P; Conway, SJ;
ACS National Meeting Book of Abstracts. 2012 243:-. doi:
PMID:

Developing chemical probes for the BET bromodomains
Hewings, DS; Wang, M; Philpott, M; Fedorov, O; Uttarkar, S; Filippakopoulos, P; Picaud, S; Vuppusetty, C; Marsden, B; Heightman, TD; Knapp, S; Brennan, P; Conway, SJ;
ACS National Meeting Book of Abstracts. 2012 243:-. doi:
PMID:

Developing small molecule inhibitors of the CREBBP bromodomain-histone interaction
Rooney, TPC; Fedorov, O; Filippakopoulos, P; Wang, M; Philpott, M; Cook, A; Heightman, TD; Knapp, S; Pryde, D; Brennan, PE; Conway, SJ;
ACS National Meeting Book of Abstracts. 2012 244:-. doi:
PMID:

A general and mild two-step procedure for the synthesis of aryl and heteroaryl sulfonamides from the corresponding iodides
Ho, DKH; Chan, L; Hooper, A; Brennan, PE;
Tetrahedron Letters. 2011 52:820 - 823-820 - 823. doi: 10.1016/j.tetlet.2010.12.050
PMID:

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
Andrews, MD; Fish, PV; Blagg, J; Brabham, TK; Brennan, PE; Bridgeland, A; Brown, AD; Bungay, PJ; Conlon, KM; Edmunds, NJ; af Forselles, K; Gibbons, CP; Green, MP; Hanton, G; Holbrook, M; Jessiman, AS; McIntosh, K; McMurray, G; Nichols, CL; Root, JA; Storer, RI; Sutton, MR; Ward, RV; Westbrook, D; Whitlock, GA;
Bioorganic and Medicinal Chemistry Letters. 2011 21:2715-2720. doi: 10.1016/j.bmcl.2010.11.120
PMID:

Potent and selective α1A adrenoceptor partial agonists—Novel imidazole frameworks
Whitlock, GA; Brennan, PE; Roberts, LR; Stobie, A;
Bioorganic and Medicinal Chemistry Letters. 2009 19:3118 - 3121-3118 - 3121. doi: 10.1016/j.bmcl.2009.03.162
PMID:

2016

Discovery of a PCAF Bromodomain Chemical Probe.
Moustakim M, Clark PG, Trulli L, Fuentes de Arriba AL, Ehebauer MT, Chaikuad A, Murphy EJ, Mendez-Johnson J, Daniels D, Hou CD, Lin YH, Walker JR, Hui R, Yang H, Dorrell L, Rogers CM, Monteiro OP, Fedorov O, Huber KV, Knapp S, Heer J, Dixon DJ, Brennan PE
Angew. Chem. Int. Ed. Engl.. 2016 . doi: 10.1002/anie.201610816
PMID: 27966810

Development of Selective CBP/P300 Benzoxazepine Bromodomain Inhibitors.
Popp, TA; Tallant, C; Rogers, C; Fedorov, O; Brennan, PE; Müller, S; Knapp, S; Bracher, F;
Journal of Medicinal Chemistry. 2016 :-. doi:
PMID: 27673482

Chemical probes and inhibitors of bromodomains outside the BET family
Moustakim, M; Clark, PGK; Hay, DA; Dixon, DJ; Brennan, PE;
MedChemComm. 2016 :-. doi: 10.1039/C6MD00373G
PMID:

BET inhibition as a new strategy for the treatment of gastric cancer.
Montenegro, RC; Clark, PG; Howarth, A; Wan, X; Ceroni, A; Siejka, P; Nunez-Alonso, GA; Monteiro, O; Rogers, C; Gamble, V; Burbano, R; Brennan, PE; Tallant, C; Ebner, D; Fedorov, O; O'Neill, E; Knapp, S; Dixon, D; Müller, S;
Oncotarget. 2016 :-. doi:
PMID: 27259267

Structural analysis of human KDM5B guides histone demethylase inhibitor development.
Johansson, C; Velupillai, S; Tumber, A; Szykowska, A; Hookway, ES; Nowak, RP; Strain-Damerell, C; Gileadi, C; Philpott, M; Burgess-Brown, N; Wu, N; Kopec, J; Nuzzi, A; Steuber, H; Egner, U; Badock, V; Munro, S; LaThangue, NB; Westaway, S; Brown, J; Athanasou, N; Prinjha, R; Brennan, PE; Oppermann, U;
Nature Chemical Biology. 2016 12:539-545. doi:
PMID: 27214403

Identification and Development of 2,3-Dihydropyrrolo[1,2-a]quinazolin-5(1H)-one Inhibitors Targeting Bromodomains within the Switch/Sucrose Nonfermenting Complex.
Sutherell, CL; Tallant, C; Monteiro, OP; Yapp, C; Fuchs, JE; Fedorov, O; Siejka, P; Müller, S; Knapp, S; Brenton, JD; Brennan, PE; Ley, SV;
Journal of Medicinal Chemistry. 2016 59:5095-5101. doi:
PMID: 27119626

Identification of a Chemical Probe for Family VIII Bromodomains through Optimization of a Fragment Hit.
Gerstenberger, BS; Trzupek, JD; Tallant, C; Fedorov, O; Filippakopoulos, P; Brennan, PE; Fedele, V; Martin, S; Picaud, S; Rogers, C; Parikh, M; Taylor, A; Samas, B; O'Mahony, A; Berg, E; Pallares, G; Torrey, AD; Treiber, DK; Samardjiev, IJ; Nasipak, BT; Padilla-Benavides, T; Wu, Q; Imbalzano, AN; Nickerson, JA; Bunnage, ME; Müller, S; Knapp, S; Owen, DR;
Journal of Medicinal Chemistry. 2016 59:4800-4811. doi:
PMID: 27115555

Structure of the Human Protein Kinase ZAK in Complex with Vemurafenib.
Mathea, S; Abdul Azeez, KR; Salah, E; Tallant, C; Wolfreys, F; Konietzny, R; Fischer, R; Lou, HJ; Brennan, PE; Schnapp, G; Pautsch, A; Kessler, BM; Turk, BE; Knapp, S;
ACS Chemical Biology. 2016 11:1595-1602. doi:
PMID: 26999302

Development of chemical probes for the bromodomains of BRD7 and BRD9.
Clark, PG; Dixon, DJ; Brennan, PE;
Drug Discovery Today: Technologies. 2016 19:73-80. doi: 10.1016/j.ddtec.2016.05.002
PMID: 27769361

A poised fragment library enables rapid synthetic expansion yielding the first reported inhibitors of PHIP(2), an atypical bromodomain
Cox, OB; Krojer, T; Collins, P; Monteiro, O; Talon, R; Bradley, A; Fedorov, O; Amin, J; Marsden, BD; Spencer, J; von Delft, F; Brennan, PE;
Chemical Science. 2016 7:2322-2330. doi: 10.1039/c5sc03115j
PMID:

Recent Progress in Histone Demethylase Inhibitors.
McAllister, TE; England, KS; Hopkinson, RJ; Brennan, PE; Kawamura, A; Schofield, CJ;
Journal of Medicinal Chemistry. 2016 59:1308-1329. doi:
PMID: 26710088

Structure-Based Identification of Inhibitory Fragments Targeting the p300/CBP-Associated Factor Bromodomain.
Chaikuad, A; Lang, S; Brennan, PE; Temperini, C; Fedorov, O; Hollander, J; Nachane, R; Abell, C; Müller, S; Siegal, G; Knapp, S;
Journal of Medicinal Chemistry. 2016 59:1648-1653. doi:
PMID: 26731131

8-Substituted Pyrido[3,4-d]pyrimidin-4(3H)-one Derivatives As Potent, Cell Permeable, KDM4 (JMJD2) and KDM5 (JARID1) Histone Lysine Demethylase Inhibitors.
Bavetsias, V; Lanigan, RM; Ruda, GF; Atrash, B; McLaughlin, MG; Tumber, A; Mok, NY; Le Bihan, YV; Dempster, S; Boxall, KJ; Jeganathan, F; Hatch, SB; Savitsky, P; Velupillai, S; Krojer, T; England, KS; Sejberg, J; Thai, C; Donovan, A; Pal, A; Scozzafava, G; Bennett, JM; Kawamura, A; Johansson, C; Szykowska, A; Gileadi, C; Burgess-Brown, NA; von Delft, F; Oppermann, U; Walters, Z; Shipley, J; Raynaud, FI; Westaway, SM; Prinjha, RK; Fedorov, O; Burke, R; Schofield, CJ; Westwood, IM; Bountra, C; Müller, S; van Montfort, RL; Brennan, PE; Blagg, J;
Journal of Medicinal Chemistry. 2016 59:1388-1409. doi:
PMID: 26741168

Deciphering the true antiproliferative target of an MK2 activation inhibitor in glioblastoma.
B, P; r, E; e, ; n, ; n, ; a, ; n, ;
Cell Death and Disease. 2016 7:e2069-. doi:
PMID: 26821065

Discovery of a Chemical Tool Inhibitor Targeting the Bromodomains of TRIM24 and BRPF.
Bennett, J; Fedorov, O; Tallant, C; Monteiro, O; Meier, J; Gamble, V; Savitsky, P; Nunez-Alonso, GA; Haendler, B; Rogers, C; Brennan, PE; Müller, S; Knapp, S;
Journal of Medicinal Chemistry. 2016 59:1642-1647. doi:
PMID: 25974391

2015

Generation of a Selective Small Molecule Inhibitor of the CBP/p300 Bromodomain for Leukemia Therapy.
Picaud, S; Fedorov, O; Thanasopoulou, A; Leonards, K; Jones, K; Meier, J; Olzscha, H; Monteiro, O; Martin, S; Philpott, M; Tumber, A; Filippakopoulos, P; Yapp, C; Wells, C; Che, KH; Bannister, A; Robson, S; Kumar, U; Parr, N; Lee, K; Lugo, D; Jeffrey, P; Taylor, S; Vecellio, ML; Bountra, C; Brennan, PE; O'Mahony, A; Velichko, S; Müller, S; Hay, D; Daniels, DL; Urh, M; La Thangue, NB; Kouzarides, T; Prinjha, R; Schwaller, J; Knapp, S;
Cancer Research. 2015 75:5106-5119. doi:
PMID: 26552700

Selective targeting of the BRG/PB1 bromodomains impairs embryonic and trophoblast stem cell maintenance.
Fedorov, O; Castex, J; Tallant, C; Owen, DR; Martin, S; Aldeghi, M; Monteiro, O; Filippakopoulos, P; Picaud, S; Trzupek, JD; Gerstenberger, BS; Bountra, C; Willmann, D; Wells, C; Philpott, M; Rogers, C; Biggin, PC; Brennan, PE; Bunnage, ME; Schüle, R; Günther, T; Knapp, S; Müller, S;
Science Advances. 2015 1:e1500723-. doi:
PMID: 26702435

Inflammatory Signaling by NOD-RIPK2 Is Inhibited by Clinically Relevant Type II Kinase Inhibitors.
Canning, P; Ruan, Q; Schwerd, T; Hrdinka, M; Maki, JL; Saleh, D; Suebsuwong, C; Ray, S; Brennan, PE; Cuny, GD; Uhlig, HH; Gyrd-Hansen, M; Degterev, A; Bullock, AN;
Chemistry and Biology. 2015 22:1174-1184. doi:
PMID: 26320862

CBP30, a selective CBP/p300 bromodomain inhibitor, suppresses human Th17 responses.
Hammitzsch, A; Tallant, C; Fedorov, O; O'Mahony, A; Brennan, PE; Hay, DA; Martinez, FO; Al-Mossawi, MH; de Wit, J; Vecellio, M; Wells, C; Wordsworth, P; Müller, S; Knapp, S; Bowness, P;
Proceedings of the National Academy of Sciences of USA. 2015 112:10768-10773. doi:
PMID: 26261308

Design and synthesis of potent and selective inhibitors of BRD7 and BRD9 bromodomains
Hay, DA; Rogers, CM; Fedorov, O; Tallant, C; Martin, S; Monteiro, OP; Mueller, S; Knapp, S; Schofield, CJ; Brennan, PE;
MedChemComm. 2015 6:1381-1386. doi: 10.1039/c5md00152h
PMID:

LP99: Discovery and Synthesis of the First Selective BRD7/9 Bromodomain Inhibitor.
Clark, PG; Vieira, LC; Tallant, C; Fedorov, O; Singleton, DC; Rogers, CM; Monteiro, OP; Bennett, JM; Baronio, R; Müller, S; Daniels, DL; Méndez, J; Knapp, S; Brennan, PE; Dixon, DJ;
Angewandte Chemie International Edition. 2015 127:6315-6319. doi:
PMID: 27346896

LP99: Discovery and Synthesis of the First Selective BRD7/9 Bromodomain Inhibitor.
Clark, PG; Vieira, LC; Tallant, C; Fedorov, O; Singleton, DC; Rogers, CM; Monteiro, OP; Bennett, JM; Baronio, R; Müller, S; Daniels, DL; Méndez, J; Knapp, S; Brennan, PE; Dixon, DJ;
Angewandte Chemie International Edition. 2015 54:6217-6221. doi:
PMID: 25864491

K2P channel gating mechanisms revealed by structures of TREK-2 and a complex with Prozac.
Dong, YY; Pike, AC; Mackenzie, A; McClenaghan, C; Aryal, P; Dong, L; Quigley, A; Grieben, M; Goubin, S; Mukhopadhyay, S; Ruda, GF; Clausen, MV; Cao, L; Brennan, PE; Burgess-Brown, NA; Sansom, MS; Tucker, SJ; Carpenter, EP;
Science. 2015 347:1256-1259. doi:
PMID: 25766236

Betti reaction enables efficient synthesis of 8-hydroxyquinoline inhibitors of 2-oxoglutarate oxygenases.
Thinnes, CC; Tumber, A; Yapp, C; Scozzafava, G; Yeh, T; Chan, MC; Tran, TA; Hsu, K; Tarhonskaya, H; Walport, LJ; Wilkins, SE; Martinez, ED; Müller, S; Pugh, CW; Ratcliffe, PJ; Brennan, PE; Kawamura, A; Schofield, CJ;
Chemical Communications. 2015 51:15458-15461. doi:
PMID: 26345662

2014

Optimisation of a triazolopyridine based histone demethylase inhibitor yields a potent and selective KDM2A (FBXL11) inhibitor.
England, KS; Tumber, A; Krojer, T; Scozzafava, G; Ng, SS; Daniel, M; Szykowska, A; Che, K; von Delft, F; Burgess-Brown, NA; Kawamura, A; Schofield, CJ; Brennan, PE;
MedChemComm. 2014 5:1879-1886. doi:
PMID: 26682034

Optimizing in vivo probes for the BET bromodomains
Jennings, LE; Hewings, DS; Humphreys, PG; Brennan, PE; Conway, SJ;
ACS National Meeting Book of Abstracts. 2014 248:-. doi:
PMID:

Discovery and optimization of small-molecule ligands for the CBP/p300 bromodomains.
Hay, DA; Fedorov, O; Martin, S; Singleton, DC; Tallant, C; Wells, C; Picaud, S; Philpott, M; Monteiro, OP; Rogers, CM; Conway, SJ; Rooney, TP; Tumber, A; Yapp, C; Filippakopoulos, P; Bunnage, ME; Müller, S; Knapp, S; Schofield, CJ; Brennan, PE;
Journal of the American Chemical Society. 2014 136:9308-9319. doi:
PMID: 24946055

A series of potent CREBBP bromodomain ligands reveals an induced-fit pocket stabilized by a cation-π interaction.
Rooney, TP; Filippakopoulos, P; Fedorov, O; Picaud, S; Cortopassi, WA; Hay, DA; Martin, S; Tumber, A; Rogers, CM; Philpott, M; Wang, M; Thompson, AL; Heightman, TD; Pryde, DC; Cook, A; Paton, RS; Müller, S; Knapp, S; Brennan, PE; Conway, SJ;
Angewandte Chemie International Edition. 2014 53:6126-6130. doi:
PMID: 24821300

Machine-assisted synthesis of modulators of the histone reader BRD9 using flow methods of chemistry and frontal affinity chromatography
Guetzoyan, L; Ingham, RJ; Nikbin, N; Rossignol, J; Wolling, M; Baumert, M; Burgess-Brown, NA; Strain-Damerell, CM; Shrestha, L; Brennan, PE; Fedorov, O; Knapp, S; Ley, SV;
MedChemComm. 2014 5:540-546. doi: 10.1039/c4md00007b
PMID:

[1,2,4]triazolo[4,3-a]phthalazines: inhibitors of diverse bromodomains.
Fedorov, O; Lingard, H; Wells, C; Monteiro, OP; Picaud, S; Keates, T; Yapp, C; Philpott, M; Martin, SJ; Felletar, I; Marsden, BD; Filippakopoulos, P; Müller, S; Knapp, S; Brennan, PE;
Journal of Medicinal Chemistry. 2014 57:462-476. doi:
PMID: 24313754

The role of protein structural analysis in the next generation sequencing era.
Yue, WW; Froese, DS; Brennan, PE;
Topics in Current Chemistry. 2014 336:67-98. doi: 10.1007/128_2012_326
PMID: 22610134

2013

Fragment-based hit identification: thinking in 3D
Morley, AD; Pugliese, A; Birchall, K; Bower, J; Brennan, P; Brown, N; Chapman, T; Drysdale, M; Gilbert, IH; Hoelder, S; Jordan, A; Ley, SV; Merritt, A; Miller, D; Swarbrick, ME; Wyatt, PG;
Drug Discovery Today. 2013 18:1221-1227. doi: 10.1016/j.drudis.2013.07.011
PMID: 23906694

RVX-208, an inhibitor of BET transcriptional regulators with selectivity for the second bromodomain.
Picaud, S; Wells, C; Felletar, I; Brotherton, D; Martin, S; Savitsky, P; Diez-Dacal, B; Philpott, M; Bountra, C; Lingard, H; Fedorov, O; Müller, S; Brennan, PE; Knapp, S; Filippakopoulos, P;
Proceedings of the National Academy of Sciences of USA. 2013 110:19754-19759. doi:
PMID: 24248379

Chemical probes for bromodomains outside the BET family
Brennan, PE; Martin, SJ; Monteiro, O; Fedorov, O; Knapp, S; Hay, D; Wells, C; Filippakopoulos, P; Picaud, S; Muller-Knapp, S; Keates, T; Yapp, C; Philpott, M; Schofield, C; Burgess-Brown, N; Shrestha, L; Strain-Damerell, C;
ACS National Meeting Book of Abstracts. 2013 246:-. doi:
PMID:

5-Carboxy-8-hydroxyquinoline is a broad spectrum 2-oxoglutarate oxygenase inhibitor which causes iron translocation
Hopkinson, RJ; Tumber, A; Yapp, C; Chowdhury, R; Aik, W; Che, KH; Li, XS; Kristensen, JBL; King, ONF; Chan, MC; Yeoh, KK; Choi, H; Walport, LJ; Thinnes, CC; Bush, JT; Lejeune, C; Rydzik, AM; Rose, NR; Bagg, EA; McDonough, MA; Krojer, TJ; Yue, WW; Ng, SS; Olsen, L; Brennan, PE; Oppermann, U; Müller, S; Klose, RJ; Ratcliffe, PJ; Schofield, CJ; Kawamura, A;
Chemical Science. 2013 4:3110-3117. doi: 10.1039/c3sc51122g
PMID: 26682036

PFI-1, a highly selective protein interaction inhibitor, targeting BET Bromodomains.
Picaud, S; Da Costa, D; Thanasopoulou, A; Filippakopoulos, P; Fish, PV; Philpott, M; Fedorov, O; Brennan, P; Bunnage, ME; Owen, DR; Bradner, JE; Taniere, P; O'Sullivan, B; Müller, S; Schwaller, J; Stankovic, T; Knapp, S;
Cancer Research. 2013 73:3336-3346. doi:
PMID: 23576556

Optimization of 3,5-dimethylisoxazole derivatives as potent bromodomain ligands.
Hewings, DS; Fedorov, O; Filippakopoulos, P; Martin, S; Picaud, S; Tumber, A; Wells, C; Olcina, MM; Freeman, K; Gill, A; Ritchie, AJ; Sheppard, DW; Russell, AJ; Hammond, EM; Knapp, S; Brennan, PE; Conway, SJ;
Journal of Medicinal Chemistry. 2013 56:3217-3227. doi:
PMID: 23517011

The design and synthesis of 5- and 6-isoxazolylbenzimidazoles as selective inhibitors of the BET bromodomains.
Hay, D; Fedorov, O; Filippakopoulos, P; Martin, S; Philpott, M; Picaud, S; Hewings, DS; Uttakar, S; Heightman, TD; Conway, SJ; Knapp, S; Brennan, PE;
MedChemComm. 2013 4:140-144. doi:
PMID: 26682033

2012

Identification of a chemical probe for bromo and extra C-terminal bromodomain inhibition through optimization of a fragment-derived hit.
Fish, PV; Filippakopoulos, P; Bish, G; Brennan, PE; Bunnage, ME; Cook, AS; Federov, O; Gerstenberger, BS; Jones, H; Knapp, S; Marsden, B; Nocka, K; Owen, DR; Philpott, M; Picaud, S; Primiano, MJ; Ralph, MJ; Sciammetta, N; Trzupek, JD;
Journal of Medicinal Chemistry. 2012 55:9831-9837. doi:
PMID: 23095041

Progress in the development and application of small molecule inhibitors of bromodomain-acetyl-lysine interactions.
Hewings, DS; Rooney, TP; Jennings, LE; Hay, DA; Schofield, CJ; Brennan, PE; Knapp, S; Conway, SJ;
Journal of Medicinal Chemistry. 2012 55:9393-9413. doi: 10.1021/jm300915b
PMID: 22924434

Developing small molecule inhibitors of the CREBBP bromodomain-histone interaction
Rooney, TPC; Fedorov, O; Filippakopoulos, P; Wang, M; Philpott, M; Cook, A; Heightman, TD; Knapp, S; Pryde, D; Brennan, PE; Conway, SJ;
ACS National Meeting Book of Abstracts. 2012 244:-. doi:
PMID:

Plant growth regulator daminozide is a selective inhibitor of human KDM2/7 histone demethylases.
Rose, NR; Woon, EC; Tumber, A; Walport, LJ; Chowdhury, R; Li, XS; King, ON; Lejeune, C; Ng, SS; Krojer, T; Chan, MC; Rydzik, AM; Hopkinson, RJ; Che, KH; Daniel, M; Strain-Damerell, C; Gileadi, C; Kochan, G; Leung, IK; Dunford, J; Yeoh, KK; Ratcliffe, PJ; Burgess-Brown, N; von Delft, F; Muller, S; Marsden, B; Brennan, PE; McDonough, MA; Oppermann, U; Klose, RJ; Schofield, CJ; Kawamura, A;
Journal of Medicinal Chemistry. 2012 55:6639-6643. doi: 10.1021/jm300677j
PMID: 22724510

3,5-Dimethylisoxazoles inhibit the bromodomain-histone protein-protein interaction
Hewings, DS; Wang, M; Philpott, M; Fedorov, O; Uttarkar, S; Filippakopoulos, P; Picaud, S; Vuppusetty, C; Marsden, B; Heightman, TD; Knapp, S; Brennan, P; Conway, SJ;
ACS National Meeting Book of Abstracts. 2012 243:-. doi:
PMID:

Developing chemical probes for the BET bromodomains
Hewings, DS; Wang, M; Philpott, M; Fedorov, O; Uttarkar, S; Filippakopoulos, P; Picaud, S; Vuppusetty, C; Marsden, B; Heightman, TD; Knapp, S; Brennan, P; Conway, SJ;
ACS National Meeting Book of Abstracts. 2012 243:-. doi:
PMID:

The therapeutic potential of acetyl-lysine and methyl-lysine effector domains
Brennan, P; Filippakopoulos, P; Knapp, S;
Drug Discovery Today: Therapeutic Strategies. 2012 9:-. doi: 10.1016/j.ddstr.2012.04.001
PMID:

2011

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
Andrews, MD; Fish, PV; Blagg, J; Brabham, TK; Brennan, PE; Bridgeland, A; Brown, AD; Bungay, PJ; Conlon, KM; Edmunds, NJ; af Forselles, K; Gibbons, CP; Green, MP; Hanton, G; Holbrook, M; Jessiman, AS; McIntosh, K; McMurray, G; Nichols, CL; Root, JA; Storer, RI; Sutton, MR; Ward, RV; Westbrook, D; Whitlock, GA;
Bioorganic and Medicinal Chemistry Letters. 2011 21:2715-2720. doi: 10.1016/j.bmcl.2010.11.120
PMID:

A general and mild two-step procedure for the synthesis of aryl and heteroaryl sulfonamides from the corresponding iodides
Ho, DKH; Chan, L; Hooper, A; Brennan, PE;
Tetrahedron Letters. 2011 52:820 - 823-820 - 823. doi: 10.1016/j.tetlet.2010.12.050
PMID:

2009

Total synthesis of rapamycin.
Ley, SV; Tackett, MN; Maddess, ML; Anderson, JC; Brennan, PE; Cappi, MW; Heer, JP; Helgen, C; Kori, M; Kouklovsky, C; Marsden, SP; Norman, J; Osborn, DP; Palomero, MA; Pavey, JB; Pinel, C; Robinson, LA; Schnaubelt, J; Scott, JS; Spilling, CD; Watanabe, H; Wesson, KE; Willis, MC;
Chemistry: A European Journal. 2009 15:2874-2914. doi: 10.1002/chem.200801656
PMID: 19204960

Potent and selective α1A adrenoceptor partial agonists—Novel imidazole frameworks
Whitlock, GA; Brennan, PE; Roberts, LR; Stobie, A;
Bioorganic and Medicinal Chemistry Letters. 2009 19:3118 - 3121-3118 - 3121. doi: 10.1016/j.bmcl.2009.03.162
PMID:

Discovery of a novel azepine series of potent and selective 5-HT2C agonists as potential treatments for urinary incontinence
Brennan, PE; Whitlock, GA; Ho, DKH; Conlon, K; McMurray, G;
Bioorganic and Medicinal Chemistry Letters. 2009 19:4999 - 5003-4999 - 5003. doi: 10.1016/j.bmcl.2009.07.063
PMID:

2007

Total Synthesis of Rapamycin
Maddess, ML; Tackett, MN; Watanabe, H; Brennan, PE; Spilling, CD; Scott, JS; Osborn, DP; Ley, SV;
Angewandte Chemie International Edition. 2007 46:591-597. doi: 10.1002/anie.200604053
PMID:

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