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.

Publications

Chemical probes and inhibitors of bromodomains outside the BET family.
Moustakim M, Clark PGK, Hay DA, Dixon DJ, Brennan PE
Medchemcomm. 2016 7(12):2246-2264. doi: 10.1039/c6md00373g
PMID: 29170712

Chemical probes and inhibitors of bromodomains outside the BET family.
Moustakim, M; Clark, PGK; Hay, DA; Dixon, DJ; Brennan, PE;
MedChemComm. 2016 7:2246-2264. doi: 10.1039/c6md00373g
PMID: 29170712

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, WS; 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

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(12):1879-1886. doi: 10.1039/C4MD00291A
PMID: 26682034

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(1):140-144. doi: 10.1039/C2MD20189E
PMID: 26682033

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
Chem. Biol.. 2015 . doi: 10.1016/j.chembiol.2015.07.017
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
Proc. Natl. Acad. Sci. U.S.A.. 2015 . doi: 10.1073/pnas.1501956112
PMID: 26261308

Discovery of a Chemical Tool Inhibitor Targeting the Bromodomains of TRIM24 and BRPF.
Bennett JM, Fedorov O, Tallant C, Monteiro OP, Meier J, Gamble V, Savitski P, Nunez-Alonso GA, Haendler B, Rogers C, Brennan PE, Müller S, Knapp S
J. Med. Chem.. 2015 . doi: 10.1021/acs.jmedchem.5b00458
PMID: 25974391

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
Angew. Chem. Int. Ed. Engl.. 2015 . doi: 10.1002/anie.201501394
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(6227):1256-1259. doi: 10.1126/science.1261512
PMID: 25766236

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
J. Am. Chem. Soc.. 2014 136(26):9308-19. doi: 10.1021/ja412434f
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
Angew. Chem. Int. Ed. Engl.. 2014 . doi: 10.1002/anie.201402750
PMID: 24821300

[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 B, Filippakopoulos P, Muller-Knapp S, Knapp S, Brennan PE
J. Med. Chem.. 2013 . doi: 10.1021/jm401568s
PMID: 24313754

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
Proc. Natl. Acad. Sci. U.S.A.. 2013 . doi: 10.1073/pnas.1310658110
PMID: 24248379

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

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 Res.. 2013 73(11):3336-3346. doi: 10.1158/0008-5472.CAN-12-3292
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: 10.1021/jm301588r
PMID: 23517011

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
J. Med. Chem.. 2012 55(22):9831-7. doi: 10.1021/jm3010515
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
J. Med. Chem.. 2012 55(22):9393-413. 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
J. Med. Chem.. 2012 55(14):6639-43. doi: 10.1021/jm300677j
PMID: 22724510

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: 21195614

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: 19394220

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, JBJ; 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

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:

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:

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:

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:

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:

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:

2020

Large eQTL meta-analysis reveals differing patterns between cerebral cortical and cerebellar brain regions
Sieberts SK, Perumal TM, Carrasquillo MM, Allen M, Reddy JS, Hoffman GE, Dang KK, Calley J, Ebert PJ, Eddy J, Wang X, Greenwood AK, Mostafavi S, Akbarian S, Bendl J, Breen MS, Brennand K, Brown L, Browne A, Buxbaum JD, Charney A, Chess A, Couto L, Crawford G, Devillers O, Devlin B, Dobbyn A, Domenici E, Filosi M, Flatow E, Francoeur N, Fullard J, Gil SE, Girdhar K, Gulyás-Kovács A, Gur R, Hahn CG, Haroutunian V, Hauberg ME, Huckins L, Jacobov R, Jiang Y, Johnson JS, Kassim B, Kim Y, Klei L, Kramer R, Lauria M, Lehner T, Lewis DA, Lipska BK, Montgomery K, Park R, Rosenbluh C, Roussos P, Ruderfer DM, Senthil G, Shah HR, Sloofman L, Song L, Stahl E, Sullivan P, Visintainer R, Wang J, Wang YC, Wiseman J, Xia E, Zhang W, Zharovsky E, Addis L, Addo SN, Airey DC, Arnold M, Bennett DA, Bi Y, Biber K, Blach C, Bradhsaw E, Brennan P, Canet-Aviles R, Cao S, Cavalla A, Chae Y, Chen WW, Cheng J, Collier DA, Dage JL, Dammer EB, Davis JW, Davis J, Drake D, Duong D, Eastwood BJ, Ehrlich M, Ellingson B, Engelmann BW, Esmaeelinieh S, Felsky D, Funk C, Gaiteri C
Scientific Data. 2020 7:-. doi: 10.1038/s41597-020-00642-8
PMID: 33046718

TargetDB: A target information aggregation tool and tractability predictor
De Cesco S, Davis JB, Brennan PE
PLOS ONE. 2020 15:e0232644-e0232644. doi: 10.1371/journal.pone.0232644
PMID: 32877430

Inhibition of Histone H3K27 Demethylases Inactivates Brachyury (TBXT) and Promotes Chordoma Cell Death
Cottone L, Cribbs AP, Khandelwal G, Wells G, Ligammari L, Philpott M, Tumber A, Lombard P, Hookway ES, Szommer T, Johansson C, Brennan PE, Pillay N, Jenner RG, Oppermann U, Flanagan AM
Cancer Research. 2020 80:4540-4551. doi: 10.1158/0008-5472.can-20-1387
PMID: 32855205

Deliberately Losing Control of C−H Activation Processes in the Design of Small-Molecule-Fragment Arrays Targeting Peroxisomal Metabolism
Khan Tareque R, Hassell-Hart S, Krojer T, Bradley A, Velupillai S, Talon R, Fairhead M, Day IJ, Bala K, Felix R, Kemmitt PD, Brennan P, von Delft F, Díaz Sáez L, Huber K, Spencer J
ChemMedChem. 2020 . doi: 10.1002/cmdc.202000543
PMID: 32812371

Targeting der kleinen GTPasen über ihre regulatorischen Proteine
Gray JL, Delft F, Brennan PE
Angewandte Chemie. 2020 132:6402-6428. doi: 10.1002/ange.201900585
PMID:

2019

Synthesis and Biological Investigation of (+)-JD1, an Organometallic BET Bromodomain Inhibitor
Hassell-Hart S, Runcie A, Krojer T, Doyle J, Lineham E, Ocasio CA, Neto BAD, Fedorov O, Marsh G, Maple H, Felix R, Banks R, Ciulli A, Picaud S, Filippakopoulos P, Von Delft F, Brennan P, Stewart HJS, Chevassut TJ, Walker M, Austin C, Morley S, Spencer J
Organometallics. 2019 . doi: 10.1021/acs.organomet.9b00750
PMID:

Structural Insights into Interaction Mechanisms of Alternative Piperazine-urea YEATS Domain Binders in MLLT1
Ni X, Heidenreich D, Christott T, Bennett J, Moustakim M, Brennan PE, Fedorov O, Knapp S, Chaikuad A
ACS Medicinal Chemistry Letters. 2019 10:1661-1666. doi: 10.1021/acsmedchemlett.9b00460
PMID: 31857843

A Chemical Probe for Tudor Domain Protein Spindlin1 to Investigate Chromatin Function
Fagan V, Johansson C, Gileadi C, Monteiro O, Dunford JE, Nibhani R, Philpott M, Malzahn J, Wells G, Farham R, Cribbs A, Halidi N, Li F, Chau I, Greschik H, Velupillai S, Allali-Hassani A, Bennett JM, Christott T, Giroud C, Lewis AM, Huber KVM, Athanasou N, Bountra C, Jung M, Schüle R, Vedadi M, Arrowsmith CH, Xiong Y, Jin J, Fedorov O, Farnie G, Brennan PE, Oppermann UCT
Journal of Medicinal Chemistry. 2019 62:9008-9025. doi: 10.1021/acs.jmedchem.9b00562
PMID: 31550156

C8-substituted pyrido[3,4-d]pyrimidin-4(3H)-ones: Studies towards the identification of potent, cell penetrant Jumonji C domain containing histone lysine demethylase 4 subfamily (KDM4)inhibitors, compound profiling in cell-based target engagement assays
Le Bihan YV, Lanigan RM, Atrash B, McLaughlin MG, Velupillai S, Malcolm AG, England KS, Ruda GF, Mok NY, Tumber A, Tomlin K, Saville H, Shehu E, McAndrew C, Carmichael LA, Bennett JM, Jeganathan F, Eve P, Donovan A, Hayes A, Wood F, Raynaud FI, Fedorov O, Brennan PE, Burke R, van Montfort RLM, Rossanese OW, Blagg J, Bavetsias V
European Journal of Medicinal Chemistry. 2019 177:316-337. doi: 10.1016/j.ejmech.2019.05.041
PMID: 31158747

Rapid Covalent-Probe Discovery by Electrophile-Fragment Screening
Resnick E, Bradley A, Gan J, Douangamath A, Krojer T, Sethi R, Geurink PP, Aimon A, Amitai G, Bellini D, Bennett J, Fairhead M, Fedorov O, Gabizon R, Gan J, Guo J, Plotnikov A, Reznik N, Ruda GF, Díaz-Sáez L, Straub VM, Szommer T, Velupillai S, Zaidman D, Zhang Y, Coker AR, Dowson CG, Barr HM, Wang C, Huber KVM, Brennan PE, Ovaa H, von Delft F, London N
Journal of the American Chemical Society. 2019 141:8951-8968. doi: 10.1021/jacs.9b02822
PMID: 31060360

Discovery of Pyrrolo[3,2- d]pyrimidin-4-one Derivatives as a New Class of Potent and Cell-Active Inhibitors of P300/CBP-Associated Factor Bromodomain.
Huang L, Li H, Li L, Niu L, Seupel R, Wu C, Cheng W, Chen C, Ding B, Brennan PE, Yang S
Journal of medicinal chemistry. 2019 62:4526-4542. doi: 10.1021/acs.jmedchem.9b00096
PMID: 30998845

ALK2 inhibitors display beneficial effects in preclinical models of ACVR1 mutant diffuse intrinsic pontine glioma
Carvalho D, Taylor KR, Olaciregui NG, Molinari V, Clarke M, Mackay A, Ruddle R, Henley A, Valenti M, Hayes A, Brandon ADH, Eccles SA, Raynaud F, Boudhar A, Monje M, Popov S, Moore AS, Mora J, Cruz O, Vinci M, Brennan PE, Bullock AN, Carcaboso AM, Jones C
Communications Biology. 2019 2:156-. doi: 10.1038/s42003-019-0420-8
PMID: 31098401

Targeting the Small GTPase Superfamily through their Regulatory Proteins.
Gray JL, von Delft F, Brennan P
Angew. Chem. Int. Ed. Engl.. 2019 . doi: 10.1002/anie.201900585
PMID: 30869179

2018

An Activity-Based Probe Targeting Non-Catalytic, Highly Conserved Amino Acid Residues within Bromodomains.
D'Ascenzio M, Pugh KM, Konietzny R, Berridge G, Tallant C, Hashem S, Monteiro O, Thomas JR, Schirle M, Knapp S, Marsden B, Fedorov O, Bountra C, Kessler BM, Brennan PE
Angew. Chem. Int. Ed. Engl.. 2018 . doi: 10.1002/anie.201807825
PMID: 30589164

Structure-Based Approach toward Identification of Inhibitory Fragments for Eleven-Nineteen-Leukemia Protein (ENL).
Heidenreich, D; Moustakim, M; Schmidt, J; Merk, D; Brennan, PE; Fedorov, O; Chaikuad, A; Knapp, S;
Journal of Medicinal Chemistry. 2018 61:10929-10934. doi: 10.1021/acs.jmedchem.8b01457
PMID: 30407816

Design, Synthesis and Characterization of Covalent KDM5 Inhibitors.
Vazquez-Rodriguez S, Wright M, Rogers CM, Cribbs A, Velupillai S, Philpott M, Lee H, Dunford JE, Huber KVM, Robers MB, Vasta JD, Thezenas ML, Bonham S, Kessler B, Bennett J, Fedorov O, Raynaud F, Donovan A, Blagg J, Bavetsias V, Oppermann U, Bountra C, Kawamura A, Brennan P
Angew. Chem. Int. Ed. Engl.. 2018 . doi: 10.1002/anie.201810179
PMID: 30431220

Target Identification Using Chemical Probes.
Moustakim M, Felce SL, Zaarour N, Farnie G, McCann FE, Brennan PE
Meth. Enzymol.. 2018 610:27-58. doi: 10.1016/bs.mie.2018.09.013
PMID: 30390803

Discovery of an MLLT1/3 YEATS Domain Chemical Probe.
Moustakim M, Christott T, Monteiro OP, Bennett J, Giroud C, Ward J, Rogers CM, Smith P, Panagakou I, Saez LD, Felce SL, Gamble V, Gileadi C, Halidi N, Heidenreich D, Chaikuad A, Knapp S, Huber KVM, Farnie G, Heer J, Manevski N, Poda G, Al-Awar R, Dixon DJ, Fedorov O, Brennan P
Angew. Chem. Int. Ed. Engl.. 2018 . doi: 10.1002/anie.201810617
PMID: 30288907

Development of 8-pyridopyrimidinone-based covalent inhibitors of KDM5B
Wright, M; Vazquez-Rodriguez, S; Brennan, P; Kawamura, A;
ACS National Meeting Book of Abstracts. 2018 256:-. doi:
PMID:

Development of a YEATS-domain chemical probe
Moustakim, M; Monteiro, O; Bennett, J; Giroud, C; Christott, T; Saez, L; Panagakou, I; Felce, L; Gamble, V; Huber, K; Farnie, G; Heer, J; Dixon, D; Brennan, P; Federov, O;
ACS National Meeting Book of Abstracts. 2018 256:-. doi:
PMID:

Development of KDM5 covalent inhibitors as chemical probes
Vazquez-Rodriguez, S; Wright, M; Brennan, P;
ACS National Meeting Book of Abstracts. 2018 256:-. doi:
PMID:

Bench-Stable Transfer Reagent Facilitates the Generation of Trifluoromethyl-sulfonimidamides.
Wright, M; Martínez-Lamenca, C; Leenaerts, JE; Brennan, PE; Trabanco, AA; Oehlrich, D;
Journal of Organic Chemistry. 2018 83:9510-9516. doi: 10.1021/acs.joc.8b01244
PMID: 29932332

Identifying Small-Molecule Binding Sites for Epigenetic Proteins at Domain-Domain Interfaces.
Bowkett, D; Talon, R; Tallant, C; Schofield, C; von Delft, F; Knapp, S; Bruton, G; Brennan, PE;
ChemMedChem. 2018 13:1051-1057. doi: 10.1002/cmdc.201800030
PMID: 29578648

Halogen-Aromatic π Interactions Modulate Inhibitor Residence Times.
Heroven, C; Georgi, V; Ganotra, GK; Brennan, P; Wolfreys, F; Wade, RC; Fernández-Montalván, AE; Chaikuad, A; Knapp, S;
Angewandte Chemie International Edition. 2018 57:7220-7224. doi: 10.1002/anie.201801666
PMID: 29601130

Discovery of a novel allosteric inhibitor scaffold for polyadenosine-diphosphate-ribose polymerase 14 (PARP14) macrodomain 2.
Moustakim M, Riedel K, Schuller M, Gehring AP, Monteiro OP, Martin SP, Fedorov O, Heer J, Dixon DJ, Elkins JM, Knapp S, Bracher F, Brennan PE
Bioorg. Med. Chem.. 2018 . doi: 10.1016/j.bmc.2018.03.020
PMID: 29567296

Mild, calcium catalysed Beckmann rearrangements.
Kiely-Collins, HJ; Sechi, I; Brennan, PE; McLaughlin, MG;
Chemical Communications. 2018 54:654-657. doi: 10.1039/c7cc09491d
PMID: 29300400

2017

The SGC beyond structural genomics: redefining the role of 3D structures by coupling genomic stratification with fragment-based discovery.
Bradley AR, Echalier A, Fairhead M, Strain-Damerell C, Brennan P, Bullock AN, Burgess-Brown NA, Carpenter EP, Gileadi O, Marsden BD, Lee WH, Yue W, Bountra C, von Delft F
Essays Biochem.. 2017 61(5):495-503. doi: 10.1042/EBC20170051
PMID: 29118096

Discovery of a Highly Selective Cell-Active Inhibitor of the Histone Lysine Demethylases KDM2/7
Gerken, PA; Wolstenhulme, JR; Tumber, A; Hatch, SB; Zhang, Y; Müller, S; Chandler, SA; Mair, B; Li, F; Nijman, SMB; Konietzny, R; Szommer, T; Yapp, C; Fedorov, O; Benesch, JLP; Vedadi, M; Kessler, BM; Kawamura, A; Brennan, PE; Smith, MD;
Angewandte Chemie International Edition. 2017 129:15761-15765. doi: 10.1002/ange.201706788
PMID:

Discovery of a Highly Selective Cell-Active Inhibitor of the Histone Lysine Demethylases KDM2/7.
Gerken, PA; Wolstenhulme, JR; Tumber, A; Hatch, SB; Zhang, Y; Müller, S; Chandler, SA; Mair, B; Li, F; Nijman, SMB; Konietzny, R; Szommer, T; Yapp, C; Fedorov, O; Benesch, JLP; Vedadi, M; Kessler, BM; Kawamura, A; Brennan, PE; Smith, MD;
Angewandte Chemie International Edition. 2017 56:15555-15559. doi: 10.1002/anie.201706788
PMID: 28976073

Selective targeting of Bromodomains of the Bromodomain-PHD Fingers family impairs osteoclast differentiation.
Meier JC, Tallant C, Fedorov O, Witwicka H, Hwang SY, van Stiphout RG, Lambert JP, Rogers C, Yapp C, Gerstenberger BS, Fedele V, Savitsky P, Heidenreich D, Daniels DL, Owen DR, Fish PV, Igoe NM, Bayle ED, Haendler B, Oppermann UCT, Buffa F, Brennan PE, Müller S, Gingras AC, Odgren PR, Birnbaum MJ, Knapp S
ACS Chem. Biol.. 2017 . doi: 10.1021/acschembio.7b00481
PMID: 28849908

BRD3 and BRD4 BET Bromodomain Proteins Differentially Regulate Skeletal Myogenesis.
Roberts TC, Etxaniz U, Dall'Agnese A, Wu SY, Chiang CM, Brennan PE, Wood MJA, Puri PL
Sci Rep. 2017 7(1):6153. doi: 10.1038/s41598-017-06483-7
PMID: 28733670

Design of a chemical probe for the Bromodomain and Plant Homeodomain Finger-containing (BRPF) family of proteins.
Igoe N, Bayle ED, Tallant C, Fedorov O, Meier JC, Savitsky P, Rogers C, Morias Y, Scholze S, Boyd H, Cunoosamy D, Andrews DM, Cheasty A, Brennan PE, Müller S, Knapp S, Fish PV
J. Med. Chem.. 2017 . doi: 10.1021/acs.jmedchem.7b00611
PMID: 28714688

Di-iodotyrosinated peptide imaging of cartilage (DIPIC)
Fowkes, MM; Borges, PDN; Brennan, PE; Vincent, TL; Lim, NH;
International Journal of Experimental Pathology. 2017 98:A7-A7. doi:
PMID:

Highly selective inhibition of histone demethylases by de novo macrocyclic peptides.
Kawamura A, Münzel M, Kojima T, Yapp C, Bhushan B, Goto Y, Tumber A, Katoh T, King ON, Passioura T, Walport LJ, Hatch SB, Madden S, Müller S, Brennan PE, Chowdhury R, Hopkinson RJ, Suga H, Schofield CJ
Nat Commun. 2017 8:14773. doi: 10.1038/ncomms14773
PMID: 28382930

Structure-based design of highly selective inhibitors of the CREB binding protein bromodomain.
Denny RA, Flick AC, Coe JW, Langille J, Basak A, Liu S, Stock IA, Sahasrabudhe P, Bonin PD, Hay DA, Brennan PE, Pletcher MT, Jones LH, Chekler EL
J. Med. Chem.. 2017 . doi: 10.1021/acs.jmedchem.6b01839
PMID: 28375629

Development of a potent and selective bromodomain chemical probe
Moustakim, M; Brennan, P; Dixon, D;
ACS National Meeting Book of Abstracts. 2017 253:-. doi:
PMID:

DEVELOPMENT OF QUANTITATIVE IN VIVO IMAGING OF ARTICULAR CARTILAGE DEGRADATION IN MURINE OSTEOARTHRITIS
Borges, PDN; Fowkes, MM; Brennan, PE; Vincent, TL; Lim, NH;
Osteoarthritis and Cartilage. 2017 25:S33-S34. doi:
PMID:

Assessing histone demethylase inhibitors in cells: lessons learned.
Hatch SB, Yapp C, Montenegro RC, Savitsky P, Gamble V, Tumber A, Ruda GF, Bavetsias V, Fedorov O, Atrash B, Raynaud F, Lanigan R, Carmichael L, Tomlin K, Burke R, Westaway SM, Brown JA, Prinjha RK, Martinez ED, Oppermann U, Schofield CJ, Bountra C, Kawamura A, Blagg J, Brennan PE, Rossanese O, Müller S
Epigenetics Chromatin. 2017 10:9. doi: 10.1186/s13072-017-0116-6
PMID: 28265301

Potent and Selective KDM5 Inhibitor Stops Cellular Demethylation of H3K4me3 at Transcription Start Sites and Proliferation of MM1S Myeloma Cells.
Tumber A, Nuzzi A, Hookway ES, Hatch SB, Velupillai S, Johansson C, Kawamura A, Savitsky P, Yapp C, Szykowska A, Wu N, Bountra C, Strain-Damerell C, Burgess-Brown NA, Ruda GF, Fedorov O, Munro S, England KS, Nowak RP, Schofield CJ, La Thangue NB, Pawlyn C, Davies F, Morgan G, Athanasou N, Müller S, Oppermann U, Brennan PE
Cell Chem Biol. 2017 . doi: 10.1016/j.chembiol.2017.02.006
PMID: 28262558

Design of a Biased Potent Small Molecule Inhibitor of the Bromodomain and PHD Finger-Containing (BRPF) Proteins Suitable for Cellular and in Vivo Studies.
Igoe N, Bayle ED, Fedorov O, Tallant C, Savitsky P, Rogers C, Owen DR, Deb G, Somervaille TC, Andrews DM, Jones N, Cheasty A, Ryder H, Brennan PE, Müller S, Knapp S, Fish PV
J. Med. Chem.. 2017 . doi: 10.1021/acs.jmedchem.6b01583
PMID: 28068087

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

Chemical probes and inhibitors of bromodomains outside the BET family.
Moustakim M, Clark PGK, Hay DA, Dixon DJ, Brennan PE
Medchemcomm. 2016 7(12):2246-2264. doi: 10.1039/c6md00373g
PMID: 29170712

PRECLINICAL EFFICACY OF ALK2 INHIBITORS IN ACVR1 MUTANT DIPG
Carvalho, D; Taylor, K; Olaciregui, NG; Valenti, M; Ruddle, R; Henley, A; Hayes, A; Brandon, ADH; MacKay, A; Molinari, V; Vinci, M; Popov, S; Brennan, P; Moore, A; Hudson, L; Hoelder, S; Bullock, A; Raynaud, F; Eccles, S; Carcaboso, AM; Jones, C;
Neuro-Oncology. 2016 18:154-154. doi:
PMID:

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

Promiscuous targeting of bromodomains by bromosporine identifies BET proteins as master regulators of primary transcription response in leukemia.
Picaud S, Leonards K, Lambert JP, Dovey O, Wells C, Fedorov O, Monteiro O, Fujisawa T, Wang CY, Lingard H, Tallant C, Nikbin N, Guetzoyan L, Ingham R, Ley SV, Brennan P, Muller S, Samsonova A, Gingras AC, Schwaller J, Vassiliou G, Knapp S, Filippakopoulos P
Sci Adv. 2016 2(10):e1600760. doi: 10.1126/sciadv.1600760
PMID: 27757418

Development of Selective CBP/P300 Benzoxazepine Bromodomain Inhibitors.
Popp TA, Tallant C, Rogers C, Fedorov O, Brennan PE, Müller S, Knapp S, Bracher F
J. Med. Chem.. 2016 . doi: 10.1021/acs.jmedchem.6b00774
PMID: 27673482

Chemical probes and inhibitors of bromodomains outside the BET family.
Moustakim, M; Clark, PGK; Hay, DA; Dixon, DJ; Brennan, PE;
MedChemComm. 2016 7:2246-2264. doi: 10.1039/c6md00373g
PMID: 29170712

Enantioselective synthesis of a chemical probe for KDM2a
Gerken, P; Smith, M; Brennan, P;
ACS National Meeting Book of Abstracts. 2016 252:-. doi:
PMID:

Advances and challenges in understanding histone demethylase biology.
Nowak RP, Tumber A, Johansson C, Che KH, Brennan P, Owen D, Oppermann U
Curr Opin Chem Biol. 2016 33:151-159. doi: 10.1016/j.cbpa.2016.06.021
PMID: 27371875

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: 10.18632/oncotarget.9766
PMID: 27259267

PRECLINICAL EFFICACY OF ALK2 INHIBITORS IN ACVR1 MUTANT DIPG
Carvalho, D; Taylor, K; Olaciregui, NG; Valenti, M; Ruddle, R; Henley, A; Hayes, A; De Haven Brandon, A; Hallsworth, A; Mackay, A; Molinari, V; Vinci, M; Popov, S; Boudhar, A; Brennan, P; Moore, A; Hudson, L; Hoelder, S; Bullock, A; Raynaud, F; Eccles, S; Carcaboso, AM; Jones, C;
Neuro-Oncology. 2016 18:63-63. doi:
PMID:

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: 10.1038/nchembio.2087
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: 10.1021/acs.jmedchem.5b01997
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 CM, Parikh MD, Taylor A, Samas BM, O'Mahony A, Berg EL, Pallares G, Torrey AV, Treiber DK, Samardjiev IJ, Nasipak BT, Padilla-Benavides T, Wu Q, Imbalzano AN, Nickerson JA, Bunnage ME, Müller S, Knapp S, Owen DR
J. Med. Chem.. 2016 . doi: 10.1021/acs.jmedchem.6b00012
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 Chem. Biol.. 2016 . doi: 10.1021/acschembio.6b00043
PMID: 26999302

Design and utilisation of a poised fragment library in the search for inhibitors of PHIP(2), an atypical bromodomain
Cox, O; Spencer, J; Brennan, P;
ACS National Meeting Book of Abstracts. 2016 251:-. doi:
PMID:

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
Chem Sci. 2016 7(3):2322-2330. doi: 10.1039/c5sc03115j
PMID: 29910922

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
J. Med. Chem.. 2016 . doi: 10.1021/acs.jmedchem.5b01635
PMID: 26741168

Dye-sensitised semiconductors modified with molecular catalysts for light-driven H2 production.
Willkomm, J; Orchard, KL; Reynal, A; Pastor, E; Durrant, JR; Reisner, E;
Chemical Society Reviews. 2016 45:9-23. doi: 10.1039/c5cs00733j
PMID: 26584204

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
J. Med. Chem.. 2016 . doi: 10.1021/acs.jmedchem.5b01719
PMID: 26731131

2015

Recent Progress in Histone Demethylase Inhibitors.
McAllister TE, England KS, Hopkinson RJ, Brennan PE, Kawamura A, Schofield CJ
J. Med. Chem.. 2015 . doi: 10.1021/acs.jmedchem.5b01758
PMID: 26710088

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
Sci Adv. 2015 1(10):e1500723. doi: 10.1126/sciadv.1500723
PMID: 26702435

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, Hing Che K, Bannister A, Robson S, Kumar U, Parr N, Lee K, Lugo D, Jeffrey P, Taylor S, Vecellio ML, Bountra C, Brennan P, O'Mahony A, Velichko S, Muller S, Hay D, Daniels DL, Urh M, La Thangue NB, Kouzarides T, Prinjha R, Schwaller J, Knapp S
Cancer Res.. 2015 . doi: 10.1158/0008-5472.CAN-15-0236
PMID: 26552700

The promise and peril of chemical probes (vol 11, pg 536, 2015)
Arrowsmith, CH; Audia, JE; Austin, C; Baell, J; Bennett, J; Blagg, J; Bountra, C; Brennan, PE; Brown, PJ; Bunnage, ME; Buser-Doepner, C; Campbell, RM; Carter, AJ; Cohen, P; Copeland, RA; Cravatt, B; Dahlin, JL; Dhanak, D; Edwards, AM; Frederiksen, M; Frye, SV; Gray, N; Grimshaw, CE; Hepworth, D; Howe, T; Huber, KVM; Jin, J; Knapp, S; Kotz, JD; Kruger, RG; Lowe, D; Mader, MM; Marsden, B; Mueller-Fahrnow, A; Mueller, S; O'Hagan, RC; Overington, JP; Owen, DR; Rosenberg, SH; Ross, R; Roth, B; Schapira, M; Schreiber, SL; Shoichet, B; Sundstroem, M; Superti-Furga, G; Taunton, J; Toledo-Sherman, L; Walpole, C; Walters, MA; Willson, TM; Workman, P; Young, RN; Zuercher, WJ;
Nature Chemical Biology. 2015 11:887-887. doi: 10.1038/nchembio.1931
PMID:

Corrigendum: The promise and peril of chemical probes.
Arrowsmith, CH; Audia, JE; Austin, C; Baell, J; Bennett, J; Blagg, J; Bountra, C; Brennan, PE; Brown, PJ; Bunnage, ME; Buser-Doepner, C; Campbell, RM; Carter, AJ; Cohen, P; Copeland, RA; Cravatt, B; Dahlin, JL; Dhanak, D; Edwards, AM; Frederiksen, M; Frye, SV; Gray, N; Grimshaw, CE; Hepworth, D; Howe, T; Huber, KVM; Jin, J; Knapp, S; Kotz, JD; Kruger, RG; Lowe, D; Mader, MM; Marsden, B; Mueller-Fahrnow, A; Müller, S; O'Hagan, RC; Overington, JP; Owen, DR; Rosenberg, SH; Ross, R; Roth, B; Schapira, M; Schreiber, SL; Shoichet, B; Sundström, M; Superti-Furga, G; Taunton, J; Toledo-Sherman, L; Walpole, C; Walters, MA; Willson, TM; Workman, P; Young, RN; Zuercher, WJ;
Nature Chemical Biology. 2015 11:887-. doi: 10.1038/nchembio1115-887c
PMID: 26485080

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: 10.1039/c5cc06095h
PMID: 26345662

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
Chem. Biol.. 2015 . doi: 10.1016/j.chembiol.2015.07.017
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
Proc. Natl. Acad. Sci. U.S.A.. 2015 . doi: 10.1073/pnas.1501956112
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, PGK; Vieira, LCC; 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: 10.1002/ange.201501394
PMID: 27346896

Discovery of a Chemical Tool Inhibitor Targeting the Bromodomains of TRIM24 and BRPF.
Bennett JM, Fedorov O, Tallant C, Monteiro OP, Meier J, Gamble V, Savitski P, Nunez-Alonso GA, Haendler B, Rogers C, Brennan PE, Müller S, Knapp S
J. Med. Chem.. 2015 . doi: 10.1021/acs.jmedchem.5b00458
PMID: 25974391

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
Angew. Chem. Int. Ed. Engl.. 2015 . doi: 10.1002/anie.201501394
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(6227):1256-1259. doi: 10.1126/science.1261512
PMID: 25766236

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(12):1879-1886. doi: 10.1039/C4MD00291A
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
J. Am. Chem. Soc.. 2014 136(26):9308-19. doi: 10.1021/ja412434f
PMID: 24946055

Multiparameter optimization in CNS drug discovery: design of pyrimido[4,5-d]azepines as potent 5-hydroxytryptamine 2C (5-HT₂C) receptor agonists with exquisite functional selectivity over 5-HT₂A and 5-HT₂B receptors.
Storer, RI; Brennan, PE; Brown, AD; Bungay, PJ; Conlon, KM; Corbett, MS; DePianta, RP; Fish, PV; Heifetz, A; Ho, DKH; Jessiman, AS; McMurray, G; de Oliveira, CAF; Roberts, LR; Root, JA; Shanmugasundaram, V; Shapiro, MJ; Skerten, M; Westbrook, D; Wheeler, S; Whitlock, GA; Wright, J;
Journal of Medicinal Chemistry. 2014 57:5258-5269. doi: 10.1021/jm5003292
PMID: 24878222

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
Angew. Chem. Int. Ed. Engl.. 2014 . doi: 10.1002/anie.201402750
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:

2013

[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 B, Filippakopoulos P, Muller-Knapp S, Knapp S, Brennan PE
J. Med. Chem.. 2013 . doi: 10.1021/jm401568s
PMID: 24313754

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
Proc. Natl. Acad. Sci. U.S.A.. 2013 . doi: 10.1073/pnas.1310658110
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, WS; 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 Res.. 2013 73(11):3336-3346. doi: 10.1158/0008-5472.CAN-12-3292
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: 10.1021/jm301588r
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(1):140-144. doi: 10.1039/C2MD20189E
PMID: 26682033

2012

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
J. Med. Chem.. 2012 55(22):9393-413. doi: 10.1021/jm300915b
PMID: 22924434

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
J. Med. Chem.. 2012 55(22):9831-7. doi: 10.1021/jm3010515
PMID: 23095041

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:

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
J. Med. Chem.. 2012 55(14):6639-43. 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:

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: 21195614

A tandem asymmetric synthesis approach for the efficient preparation of enantiomerically pure 9-(hydroxyethyl) anthracene
Ball, JC; Brennan, P; Elsunaki, TM; Jaunet, A; Jones, S;
Tetrahedron: Asymmetry. 2011 22:253-255. doi: 10.1016/j.tetasy.2011.01.019
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, JBJ; 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: 19394220

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:

2003

Palladium-containing perovskites: recoverable and reuseable catalysts for Suzuki couplings.
Smith, MD; Stepan, AF; Ramarao, C; Brennan, PE; Ley, SV;
Chemical Communications. 2003 :2652-2653. doi: 10.1039/b308465e
PMID: 14649794

Synthesis of carbohydrate derivatives using solid-phase work-up and scavenging techniques.
MacCoss, RN; Brennan, PE; Ley, SV;
Organic and Biomolecular Chemistry. 2003 1:2029-2031. doi: 10.1039/b303951j
PMID: 12945889

Synthesis of carbohydrate derivatives using clean chemistry.
MacCoss, RN; Brennan, PE; Ley, SV;
ACS National Meeting Book of Abstracts. 2003 225:U297-U297. doi:
PMID:

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