Panagis Filippakopoulos

Principal Investigator

University of Oxford

Panagis obtained his BSc. in Chemistry from the Aristotelian University of Thessaloniki. He carried out his doctoral studies in Inorganic Chemistry at the University of Michigan with Prof. Dimitri Coucouvanis and received his PhD in 2004. He moved to Oxford University in the UK at the Structural Genomics Consortium where he focused on protein crystallography and biophysics, first as a postdoctoral scientist until 2007, then as a Team Leader until 2011. In December 2011 he received a Research Career Development Fellowship Award from the Wellcome Trust and took a post as a Principal Investigator at the Nuffield Department of Medicine in Oxford University. In November 2012 he became an affiliate of the Ludwig Institute for Cancer Research (LICR) in Oxford. His research interest is focused on structural comparisons of entire protein families and the discovery of shared and distinct mechanisms that determine substrate recognition and protein regulation, as well as the structure-guided design of specific inhibitors that modulate the function of proteins involved in epigenetic signaling, aiming to target them in disease.

Research Areas

The goal of our research is to address the structural and functional role of BET (Bromo and Extra Terminal) proteins in transcription initiation by establishing the network of their interactions and their structural involvement in the assembly of the transcriptional machinery. Importantly, we aim to understand how this network of interactions is perturbed in cancer, when members of the BET family are found fused to the NUT protein, acting as molecular switches, resulting in so called NUT-midline carcinomas (NMCs). Research of this type will help demystify cell cycle progression providing a link between cellular signalling and readout of epigenetic marks facilitating the design of translational research projects that aim to target BET proteins.

Publications

What Is the BET on Solid Tumors?
Filippakopoulos P
J. Clin. Oncol.. 2018 JCO2018788695. doi: 10.1200/JCO.2018.78.8695
PMID: 29847297

Functions of bromodomain-containing proteins and their roles in homeostasis and cancer.
Fujisawa T, Filippakopoulos P
Nat. Rev. Mol. Cell Biol.. 2017 . doi: 10.1038/nrm.2016.143
PMID: 28053347

Epigenetic targeting of bromodomain protein BRD4 counteracts cancer cachexia and prolongs survival.
Segatto M, Fittipaldi R, Pin F, Sartori R, Dae Ko K, Zare H, Fenizia C, Zanchettin G, Pierobon ES, Hatakeyama S, Sperti C, Merigliano S, Sandri M, Filippakopoulos P, Costelli P, Sartorelli V, Caretti G
Nat Commun. 2017 8(1):1707. doi: 10.1038/s41467-017-01645-7
PMID: 29167426

Multivalent Histone and DNA Engagement by a PHD/BRD/PWWP Triple Reader Cassette Recruits ZMYND8 to K14ac-Rich Chromatin.
Savitsky P, Krojer T, Fujisawa T, Lambert JP, Picaud S, Wang CY, Shanle EK, Krajewski K, Friedrichsen H, Kanapin A, Goding C, Schapira M, Samsonova A, Strahl BD, Gingras AC, Filippakopoulos P
Cell Rep. 2016 17(10):2724-2737. doi: 10.1016/j.celrep.2016.11.014
PMID: 27926874

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

Beating the odds: BETs in disease.
Wang CY, Filippakopoulos P
Trends Biochem. Sci.. 2015 . doi: 10.1016/j.tibs.2015.06.002
PMID: 26145250

Targeting bromodomains: epigenetic readers of lysine acetylation.
Filippakopoulos P, Knapp S
Nat Rev Drug Discov. 2014 13(5):337-56. doi: 10.1038/nrd4286
PMID: 24751816

Dual kinase-bromodomain inhibitors for rationally designed polypharmacology.
Ciceri P, Müller S, O'Mahony A, Fedorov O, Filippakopoulos P, Hunt JP, Lasater EA, Pallares G, Picaud S, Wells C, Martin S, Wodicka LM, Shah NP, Treiber DK, Knapp S
Nat. Chem. Biol.. 2014 10(4):305-12. doi: 10.1038/nchembio.1471
PMID: 24584101

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

Small-molecule inhibition of BRDT for male contraception.
Matzuk MM, McKeown MR, Filippakopoulos P, Li Q, Ma L, Agno JE, Lemieux ME, Picaud S, Yu RN, Qi J, Knapp S, Bradner JE
Cell. 2012 150(4):673-84. doi: 10.1016/j.cell.2012.06.045
PMID: 22901802

Selective inhibition of BET bromodomains.
Filippakopoulos P, Qi J, Picaud S, Shen Y, Smith WB, Fedorov O, Morse EM, Keates T, Hickman TT, Felletar I, Philpott M, Munro S, McKeown MR, Wang Y, Christie AL, West N, Cameron MJ, Schwartz B, Heightman TD, La Thangue N, French CA, Wiest O, Kung AL, Knapp S, Bradner JE
Nature. 2010 468(7327):1067-73. doi: 10.1038/nature09504
PMID: 20871596

Structural coupling of SH2-kinase domains links Fes and Abl substrate recognition and kinase activation.
Filippakopoulos P, Kofler M, Hantschel O, Gish GD, Grebien F, Salah E, Neudecker P, Kay LE, Turk BE, Superti-Furga G, Pawson T, Knapp S
Cell. 2008 134(5):793-803. doi: 10.1016/j.cell.2008.07.047
PMID: 18775312

2020

Identification of a PGXPP degron motif in dishevelled and structural basis for its binding to the E3 ligase KLHL12
Chen Z, Wasney GA, Picaud S, Filippakopoulos P, Vedadi M, D'Angiolella V, Bullock AN
Open Biol. 2020 10(6):200041. doi: 10.1098/rsob.200041
PMID: 32574548

Effects of epigenetic pathway inhibitors on corticotroph tumour AtT20 cells
LINES K, FILIPPAKOPOULOS P, STEVENSON M, Lockstone H, WRIGHT B, BUCK D, BOUNTRA C, THAKKER RV
Endocrine-Related Cancer. 2020 27:163-174. doi: 10.1530/ERC-19-0448
PMID: 31935194

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:

Emerging tools to investigate bromodomain functions
Kougnassoukou Tchara PE, Filippakopoulos P, Lambert JP
Methods. 2019 . doi: 10.1016/j.ymeth.2019.11.003
PMID: 31726225

Structural basis for recruitment of DAPK1 to the KLHL20 E3 ligase
BULLOCK A, CHEN Z, PICAUD S, FILIPPAKOPOULOS P, D'ANGIOLELLA V
Structure. 2019 27:1395-1404.e4. doi: 10.1016/j.str.2019.06.005
PMID: 31279627

Evaluation of linker length effects on a BET bromodomain probe
Traquete R, Henderson E, Picaud S, Cal PMSD, Sieglitz F, Rodrigues T, Oliveira R, Filippakopoulos P, Bernardes GJL
Chemical Communications. 2019 55:10128-10131. doi: 10.1039/c9cc05054j
PMID: 31386708

A Tail-Based Mechanism Drives Nucleosome Demethylation by the LSD2/NPAC Multimeric Complex
Marabelli C, Marrocco B, Pilotto S, Chittori S, Picaud S, Marchese S, Ciossani G, Forneris F, Filippakopoulos P, Schoehn G, Rhodes D, Subramaniam S, Mattevi A
Cell Reports. 2019 27:387-399.e7. doi: 10.1016/j.celrep.2019.03.061
PMID: 30970244

Development and preclinical validation of a novel covalent ubiquitin receptor Rpn13 degrader in multiple myeloma
Song Y, Park PMC, Wu L, Ray A, Picaud S, Li D, Wimalasena VK, Du T, Filippakopoulos P, Anderson KC, Qi J, Chauhan D
Leukemia. 2019 . doi: 10.1038/s41375-019-0467-z
PMID: 30962579

2018

Interactome Rewiring Following Pharmacological Targeting of BET Bromodomains.
Lambert JP, Picaud S, Fujisawa T, Hou H, Savitsky P, Uusküla-Reimand L, Gupta GD, Abdouni H, Lin ZY, Tucholska M, Knight JDR, Gonzalez-Badillo B, St-Denis N, Newman JA, Stucki M, Pelletier L, Bandeira N, Wilson MD, Filippakopoulos P, Gingras AC
Mol. Cell. 2018 . doi: 10.1016/j.molcel.2018.11.006
PMID: 30554943

Direct interaction between the PRDM3 and PRDM16 tumor suppressors and the NuRD chromatin remodeling complex.
Ivanochko, D; Halabelian, L; Henderson, E; Savitsky, P; Jain, H; Marcon, E; Duan, S; Hutchinson, A; Seitova, A; Barsyte-Lovejoy, D; Filippakopoulos, P; Greenblatt, J; Lima-Fernandes, E; Arrowsmith, CH;
Nucleic Acids Research. 2018 :-. doi: 10.1093/nar/gky1192
PMID: 30462309

Nut Directs p300-Dependent, Genome-Wide H4 Hyperacetylation in Male Germ Cells.
Shiota H, Barral S, Buchou T, Tan M, Couté Y, Charbonnier G, Reynoird N, Boussouar F, Gérard M, Zhu M, Bargier L, Puthier D, Chuffart F, Bourova-Flin E, Picaud S, Filippakopoulos P, Goudarzi A, Ibrahim Z, Panne D, Rousseaux S, Zhao Y, Khochbin S
Cell Rep. 2018 24(13):3477-3487.e6. doi: 10.1016/j.celrep.2018.08.069
PMID: 30257209

BRAF/MAPK and GSK3 signaling converges to control MITF nuclear export.
Ngeow KC, Friedrichsen HJ, Li L, Zeng Z, Andrews S, Volpon L, Brunsdon H, Berridge G, Picaud S, Fischer R, Lisle R, Knapp S, Filippakopoulos P, Knowles H, Steingrímsson E, Borden KLB, Patton EE, Goding CR
Proc. Natl. Acad. Sci. U.S.A.. 2018 . doi: 10.1073/pnas.1810498115
PMID: 30150413

Small molecule inhibitors reveal an indispensable scaffolding role of RIPK2 in NOD2 signaling.
Hrdinka M, Schlicher L, Dai B, Pinkas DM, Bufton JC, Picaud S, Ward JA, Rogers C, Suebsuwong C, Nikhar S, Cuny GD, Huber KV, Filippakopoulos P, Bullock AN, Degterev A, Gyrd-Hansen M
EMBO J.. 2018 . doi: 10.15252/embj.201899372
PMID: 30026309

A TFEB nuclear export signal integrates amino acid supply and glucose availability.
Li L, Friedrichsen HJ, Andrews S, Picaud S, Volpon L, Ngeow K, Berridge G, Fischer R, Borden KLB, Filippakopoulos P, Goding CR
Nat Commun. 2018 9(1):2685. doi: 10.1038/s41467-018-04849-7
PMID: 29992949

What Is the BET on Solid Tumors?
Filippakopoulos P
J. Clin. Oncol.. 2018 JCO2018788695. doi: 10.1200/JCO.2018.78.8695
PMID: 29847297

BET bromodomain ligands: Probing the WPF shelf to improve BRD4 bromodomain affinity and metabolic stability.
Jennings LE, Schiedel M, Hewings DS, Picaud S, Laurin CMC, Bruno PA, Bluck JP, Scorah AR, See L, Reynolds JK, Moroglu M, Mistry IN, Hicks A, Guzanov P, Clayton J, Evans CNG, Stazi G, Biggin PC, Mapp AK, Hammond EM, Humphreys PG, Filippakopoulos P, Conway SJ
Bioorg. Med. Chem.. 2018 . doi: 10.1016/j.bmc.2018.05.003
PMID: 29776834

The C-terminal extension landscape of naturally presented HLA-I ligands.
Guillaume P, Picaud S, Baumgaertner P, Montandon N, Schmidt J, Speiser DE, Coukos G, Bassani-Sternberg M, Filippakopoulos P, Gfeller D
Proc. Natl. Acad. Sci. U.S.A.. 2018 . doi: 10.1073/pnas.1717277115
PMID: 29712860

Tryptophan-Mediated Interactions between Tristetraprolin and the CNOT9 Subunit Are Required for CCR4-NOT Deadenylase Complex Recruitment.
Bulbrook, D; Brazier, H; Mahajan, P; Kliszczak, M; Fedorov, O; Marchese, FP; Aubareda, A; Chalk, R; Picaud, S; Strain-Damerell, C; Filippakopoulos, P; Gileadi, O; Clark, AR; Yue, WW; Burgess-Brown, NA; Dean, JLE;
Journal of Molecular Biology. 2018 430:722-736. doi: 10.1016/j.jmb.2017.12.018
PMID: 29291391

2017

Epigenetic targeting of bromodomain protein BRD4 counteracts cancer cachexia and prolongs survival.
Segatto M, Fittipaldi R, Pin F, Sartori R, Dae Ko K, Zare H, Fenizia C, Zanchettin G, Pierobon ES, Hatakeyama S, Sperti C, Merigliano S, Sandri M, Filippakopoulos P, Costelli P, Sartorelli V, Caretti G
Nat Commun. 2017 8(1):1707. doi: 10.1038/s41467-017-01645-7
PMID: 29167426

Correction for Bagarova et al., "Constitutively Active ALK2 Receptor Mutants Require Type II Receptor Cooperation".
Bagarova, J; Vonner, AJ; Armstrong, KA; Börgermann, J; Lai, CSC; Deng, DY; Beppu, H; Alfano, I; Filippakopoulos, P; Morrell, NW; Bullock, AN; Knaus, P; Mishina, Y; Yu, PB;
Molecular and Cellular Biology. 2017 37:-. doi: 10.1128/mcb.00284-17
PMID: 28899999

Structures of PGAM5 Provide Insight into Active Site Plasticity and Multimeric Assembly.
Chaikuad A, Filippakopoulos P, Marcsisin SR, Picaud S, Schröder M, Sekine S, Ichijo H, Engen JR, Takeda K, Knapp S
Structure. 2017 . doi: 10.1016/j.str.2017.05.020
PMID: 28648608

Epigenetic pathway inhibitors represent potential drugs for treating pancreatic and bronchial neuroendocrine tumors.
Lines, KE; Stevenson, M; Filippakopoulos, P; Müller, S; Lockstone, HE; Wright, B; Grozinsky-Glasberg, S; Grossman, AB; Knapp, S; Buck, D; Bountra, C; Thakker, RV;
Oncogenesis. 2017 6:e332-. doi: 10.1038/oncsis.2017.30
PMID: 28504695

MOB1 mediated phospho-recognition in the core mammalian Hippo pathway.
Couzens AL, Xiong S, Knight JD, Mao DY, Guettler S, Picaud S, Kurinov I, Filippakopoulos P, Sicheri F, Gingras AC
Mol. Cell Proteomics. 2017 . doi: 10.1074/mcp.M116.065490
PMID: 28373298

Functions of bromodomain-containing proteins and their roles in homeostasis and cancer.
Fujisawa T, Filippakopoulos P
Nat. Rev. Mol. Cell Biol.. 2017 . doi: 10.1038/nrm.2016.143
PMID: 28053347

2016

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

Multivalent Histone and DNA Engagement by a PHD/BRD/PWWP Triple Reader Cassette Recruits ZMYND8 to K14ac-Rich Chromatin.
Savitsky P, Krojer T, Fujisawa T, Lambert JP, Picaud S, Wang CY, Shanle EK, Krajewski K, Friedrichsen H, Kanapin A, Goding C, Schapira M, Samsonova A, Strahl BD, Gingras AC, Filippakopoulos P
Cell Rep. 2016 17(10):2724-2737. doi: 10.1016/j.celrep.2016.11.014
PMID: 27926874

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

Discovery and Optimization of a Selective Ligand for the Switch/Sucrose Nonfermenting-Related Bromodomains of Polybromo Protein-1 by the Use of Virtual Screening and Hydration Analysis.
Myrianthopoulos, V; Gaboriaud-Kolar, N; Tallant, C; Hall, M-L; Grigoriou, S; Brownlee, PM; Fedorov, O; Rogers, C; Heidenreich, D; Wanior, M; Drosos, N; Mexia, N; Savitsky, P; Bagratuni, T; Kastritis, E; Terpos, E; Filippakopoulos, P; Müller, S; Skaltsounis, A-L; Downs, JA; Knapp, S; Mikros, E;
Journal of Medicinal Chemistry. 2016 59:8787-8803. doi: 10.1021/acs.jmedchem.6b00355
PMID: 27617704

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

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

Dual Targeting of Bromodomain and Extraterminal Domain Proteins, and WNT or MAPK Signaling, Inhibits c-MYC Expression and Proliferation of Colorectal Cancer Cells.
Tögel, L; Nightingale, R; Chueh, AC; Jayachandran, A; Tran, H; Phesse, T; Wu, R; Sieber, OM; Arango, D; Dhillon, AS; Dawson, MA; Diez-Dacal, B; Gahman, TC; Filippakopoulos, P; Shiau, AK; Mariadason, JM;
Molecular Cancer Therapeutics. 2016 15:1217-1226. doi: 10.1158/1535-7163.mct-15-0724
PMID: 26983878

2015

Regulation of signaling interactomes in cancer
Lambert, J-P; Zhou, Y; Couzens, A; Tsou, C-C; Picaud, S; Ivosev, G; Tate, S; Nesvizhskii, A; Filippakopoulos, P; Gingras, A-C;
Cancer Research. 2015 75:-. doi: 10.1158/1538-7445.COMPSYSBIO-IA19
PMID:

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

BET inhibition upregulates SIRT1 and alleviates inflammatory responses.
Suuronen T, Pesonen M, Filippakopoulos P, Salminen A, Jarho EM, Lahtela-Kakkonen M, Kokkola T
Chembiochem. 2015 . doi: 10.1002/cbic.201500272
PMID: 26212199

Beating the odds: BETs in disease.
Wang CY, Filippakopoulos P
Trends Biochem. Sci.. 2015 . doi: 10.1016/j.tibs.2015.06.002
PMID: 26145250

9H-purine scaffold reveals induced-fit pocket plasticity of the BRD9 bromodomain.
Picaud, S; Strocchia, M; Terracciano, S; Lauro, G; Mendez, J; Daniels, DL; Riccio, R; Bifulco, G; Bruno, I; Filippakopoulos, P;
Journal of Medicinal Chemistry. 2015 58:2718-2736. doi: 10.1021/jm501893k
PMID: 25703523

Genome-wide profiling of molecular recognition of histone PTMs
Filippakopoulos, P; Knapp, S;
. 2015 :173-184. doi: 10.1007/978-3-319-18102-8_8
PMID:

SPOTing Acetyl-Lysine Dependent Interactions.
Picaud S, Filippakopoulos P
Microarrays (Basel). 2015 4(3):370-88. doi: 10.3390/microarrays4030370
PMID: 27600229

2014

Molecular Basis of Histone Tail Recognition by Human TIP5 PHD Finger and Bromodomain of the Chromatin Remodeling Complex NoRC.
Tallant C, Valentini E, Fedorov O, Overvoorde L, Ferguson FM, Filippakopoulos P, Svergun DI, Knapp S, Ciulli A
Structure. 2014 . doi: 10.1016/j.str.2014.10.017
PMID: 25533489

Dual kinase/bromodomain inhibitors for rationally designed polypharmacology
Quinn, ER; Ciceri, P; Mueller-Knapp, S; O'Mahony, A; Fedorov, O; Filippakopoulos, P; Hunt, JP; Lasater, EA; Pallares, G; Picaud, S; Wells, C; Wodicka, LM; Shah, NP; Knapp, S; Treiber, DK;
Cancer Research. 2014 74:-. doi: 10.1158/1538-7445.AM2014-5387
PMID:

Corrigendum: Dual kinase-bromodomain inhibitors for rationally designed polypharmacology.
Ciceri P, Müller S, O'Mahony A, Fedorov O, Filippakopoulos P, Hunt JP, Lasater EA, Pallares G, Picaud S, Wells C, Martin S, Wodicka LM, Shah NP, Treiber DK, Knapp S
Nat. Chem. Biol.. 2014 10(8):692. doi:
PMID: 25036311

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

Targeting bromodomains: epigenetic readers of lysine acetylation.
Filippakopoulos P, Knapp S
Nat Rev Drug Discov. 2014 13(5):337-56. doi: 10.1038/nrd4286
PMID: 24751816

Dual kinase-bromodomain inhibitors for rationally designed polypharmacology.
Ciceri P, Müller S, O'Mahony A, Fedorov O, Filippakopoulos P, Hunt JP, Lasater EA, Pallares G, Picaud S, Wells C, Martin S, Wodicka LM, Shah NP, Treiber DK, Knapp S
Nat. Chem. Biol.. 2014 10(4):305-12. doi: 10.1038/nchembio.1471
PMID: 24584101

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

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

Discovery of Novel Small-Molecule Inhibitors of BRD4 Using Structure-Based Virtual Screening.
Vidler LR, Filippakopoulos P, Fedorov O, Picaud S, Martin S, Tomsett M, Woodward H, Brown N, Knapp S, Hoelder S
J. Med. Chem.. 2013 . doi: 10.1021/jm4011302
PMID: 24090311

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

Constitutively Active ALK2 Receptor Mutants Require Type II Receptor Cooperation.
Bagarova J, Vonner AJ, Armstrong KA, Börgermann J, Lai CS, Deng DY, Beppu H, Alfano I, Filippakopoulos P, Morrell NW, Bullock AN, Knaus P, Mishina Y, Yu PB
Mol. Cell. Biol.. 2013 33(12):2413-24. doi: 10.1128/MCB.01595-12
PMID: 23572558

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

Novel Inverse Binding Mode of Indirubin Derivatives Yields Improved Selectivity for DYRK Kinases.
Myrianthopoulos V, Kritsanida M, Gaboriaud-Kolar N, Magiatis P, Ferandin Y, Durieu E, Lozach O, Cappel D, Soundararajan M, Filippakopoulos P, Sherman W, Knapp S, Meijer L, Mikros E, Skaltsounis AL
ACS Med Chem Lett. 2013 4(1):22-26. doi: 10.1021/ml300207a
PMID: 23336033

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

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

Selectivity, cocrystal structures, and neuroprotective properties of leucettines, a family of protein kinase inhibitors derived from the marine sponge alkaloid leucettamine B.
Tahtouh T, Elkins JM, Filippakopoulos P, Soundararajan M, Burgy G, Durieu E, Cochet C, Schmid RS, Lo DC, Delhommel F, Oberholzer AE, Pearl LH, Carreaux F, Bazureau JP, Knapp S, Meijer L
J. Med. Chem.. 2012 55(21):9312-30. doi: 10.1021/jm301034u
PMID: 22998443

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:

Small-molecule inhibition of BRDT for male contraception.
Matzuk MM, McKeown MR, Filippakopoulos P, Li Q, Ma L, Agno JE, Lemieux ME, Picaud S, Yu RN, Qi J, Knapp S, Bradner JE
Cell. 2012 150(4):673-84. doi: 10.1016/j.cell.2012.06.045
PMID: 22901802

The bromodomain interaction module
Filippakopoulos, P; Knapp, S;
FEBS Letters. 2012 586:2692-2704. doi: 10.1016/j.febslet.2012.04.045
PMID:

Small-molecule inhibitors of the c-Fes protein-tyrosine kinase.
Hellwig S, Miduturu CV, Kanda S, Zhang J, Filippakopoulos P, Salah E, Deng X, Choi HG, Zhou W, Hur W, Knapp S, Gray NS, Smithgall TE
Chem. Biol.. 2012 19(4):529-40. doi: 10.1016/j.chembiol.2012.01.020
PMID: 22520759

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:

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:

Benzodiazepines and benzotriazepines as protein interaction inhibitors targeting bromodomains of the BET family.
Filippakopoulos P, Picaud S, Fedorov O, Keller M, Wrobel M, Morgenstern O, Bracher F, Knapp S
Bioorg. Med. Chem.. 2012 20(6):1878-86. doi: 10.1016/j.bmc.2011.10.080
PMID: 22137933

7,8-dichloro-1-oxo-β-carbolines as a versatile scaffold for the development of potent and selective kinase inhibitors with unusual binding modes.
Huber K, Brault L, Fedorov O, Gasser C, Filippakopoulos P, Bullock AN, Fabbro D, Trappe J, Schwaller J, Knapp S, Bracher F
J. Med. Chem.. 2012 55(1):403-13. doi: 10.1021/jm201286z
PMID: 22136433

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

2011

Bromodomain-peptide displacement assays for interactome mapping and inhibitor discovery.
Philpott, M; Yang, J; Tumber, T; Fedorov, O; Uttarkar, S; Filippakopoulos, P; Picaud, S; Keates, T; Felletar, I; Ciulli, A; Knapp, S; Heightman, TD;
Molecular BioSystems. 2011 7:2899-2908. doi: 10.1039/c1mb05099k
PMID:

Bromodomains as therapeutic targets.
Muller S, Filippakopoulos P, Knapp S
Expert Rev Mol Med. 2011 13:e29. doi: 10.1017/S1462399411001992
PMID: 21933453

High-throughput kinase profiling: a more efficient approach toward the discovery of new kinase inhibitors.
Miduturu CV, Deng X, Kwiatkowski N, Yang W, Brault L, Filippakopoulos P, Chung E, Yang Q, Schwaller J, Knapp S, King RW, Lee JD, Herrgard S, Zarrinkar P, Gray NS
Chem. Biol.. 2011 18(7):868-79. doi: 10.1016/j.chembiol.2011.05.010
PMID: 21802008

Leucettines, a class of potent inhibitors of cdc2-like kinases and dual specificity, tyrosine phosphorylation regulated kinases derived from the marine sponge leucettamine B: modulation of alternative pre-RNA splicing.
Debdab M, Carreaux F, Renault S, Soundararajan M, Fedorov O, Filippakopoulos P, Lozach O, Babault L, Tahtouh T, Baratte B, Ogawa Y, Hagiwara M, Eisenreich A, Rauch U, Knapp S, Meijer L, Bazureau JP
J. Med. Chem.. 2011 54(12):4172-86. doi: 10.1021/jm200274d
PMID: 21615147

BET bromodomain inhibitors for cancer therapy
Qi, J; Filippakopoulos, P; McKeown, M; Shaw, KL; Smith, WB; French, CA; Kung, AL; Knapp, S; Bradner, JE;
Cancer Research. 2011 71:-. doi: 10.1158/1538-7445.AM2011-2318
PMID:

Structurally sophisticated octahedral metal complexes as highly selective protein kinase inhibitors
Feng, L; Geisselbrecht, Y; Blanck, S; Wilbuer, A; Atilla-Gokcumen, GE; Filippakopoulos, P; Kräling, K; Celik, MA; Harms, K; Maksimoska, J; Marmorstein, R; Frenking, G; Knapp, S; Essen, LO; Meggers, E;
Journal of the American Chemical Society. 2011 133:5976-5986. doi: 10.1021/ja1112996
PMID: 21446733

Specific CLK inhibitors from a novel chemotype for regulation of alternative splicing.
Fedorov O, Huber K, Eisenreich A, Filippakopoulos P, King O, Bullock AN, Szklarczyk D, Jensen LJ, Fabbro D, Trappe J, Rauch U, Bracher F, Knapp S
Chem. Biol.. 2011 18(1):67-76. doi: 10.1016/j.chembiol.2010.11.009
PMID: 21276940

The crystal structure of human GLRX5: iron-sulfur cluster co-ordination, tetrameric assembly and monomer activity.
Johansson C, Roos AK, Montano SJ, Sengupta R, Filippakopoulos P, Guo K, von Delft F, Holmgren A, Oppermann U, Kavanagh KL
Biochem. J.. 2011 433(2):303-11. doi: 10.1042/BJ20101286
PMID: 21029046

2010

Selective inhibition of BET bromodomains.
Filippakopoulos P, Qi J, Picaud S, Shen Y, Smith WB, Fedorov O, Morse EM, Keates T, Hickman TT, Felletar I, Philpott M, Munro S, McKeown MR, Wang Y, Christie AL, West N, Cameron MJ, Schwartz B, Heightman TD, La Thangue N, French CA, Wiest O, Kung AL, Knapp S, Bradner JE
Nature. 2010 468(7327):1067-73. doi: 10.1038/nature09504
PMID: 20871596

Structural basis for Par-4 recognition by the SPRY domain- and SOCS box-containing proteins SPSB1, SPSB2, and SPSB4.
Filippakopoulos P, Low A, Sharpe TD, Uppenberg J, Yao S, Kuang Z, Savitsky P, Lewis RS, Nicholson SE, Norton RS, Bullock AN
J. Mol. Biol.. 2010 401(3):389-402. doi: 10.1016/j.jmb.2010.06.017
PMID: 20561531

New potent dual inhibitors of CK2 and Pim kinases: discovery and structural insights.
López-Ramos M, Prudent R, Moucadel V, Sautel CF, Barette C, Lafanechère L, Mouawad L, Grierson D, Schmidt F, Florent JC, Filippakopoulos P, Bullock AN, Knapp S, Reiser JB, Cochet C
FASEB J.. 2010 24(9):3171-85. doi: 10.1096/fj.09-143743
PMID: 20400536

Small-molecule kinase inhibitors provide insight into Mps1 cell cycle function.
Kwiatkowski N, Jelluma N, Filippakopoulos P, Soundararajan M, Manak MS, Kwon M, Choi HG, Sim T, Deveraux QL, Rottmann S, Pellman D, Shah JV, Kops GJ, Knapp S, Gray NS
Nat. Chem. Biol.. 2010 6(5):359-68. doi: 10.1038/nchembio.345
PMID: 20383151

Small molecule inhibitors of the Fes non-receptor tyrosine kinase
Hellwig, S; Zhang, J; Filippakopoulos, P; Salah, E; Knapp, S; Gray, NS; Smithgall, TE;
Cancer Research. 2010 70:-. doi: 10.1158/1538-7445.AM10-3683
PMID:

2009

Structure and functional characterization of the atypical human kinase haspin.
Eswaran J, Patnaik D, Filippakopoulos P, Wang F, Stein RL, Murray JW, Higgins JM, Knapp S
Proc. Natl. Acad. Sci. U.S.A.. 2009 106(48):20198-203. doi: 10.1073/pnas.0901989106
PMID: 19918057

SH2 domains: modulators of nonreceptor tyrosine kinase activity.
Filippakopoulos P, Müller S, Knapp S
Curr. Opin. Struct. Biol.. 2009 19(6):643-9. doi: 10.1016/j.sbi.2009.10.001
PMID: 19926274

Synthesis, kinase inhibitory potencies, and in vitro antiproliferative evaluation of new Pim kinase inhibitors.
Akué-Gédu R, Rossignol E, Azzaro S, Knapp S, Filippakopoulos P, Bullock AN, Bain J, Cohen P, Prudhomme M, Anizon F, Moreau P
J. Med. Chem.. 2009 52(20):6369-81. doi: 10.1021/jm901018f
PMID: 19788246

Large-scale structural analysis of the classical human protein tyrosine phosphatome.
Barr AJ, Ugochukwu E, Lee WH, King ON, Filippakopoulos P, Alfano I, Savitsky P, Burgess-Brown NA, Müller S, Knapp S
Cell. 2009 136(2):352-63. doi: 10.1016/j.cell.2008.11.038
PMID: 19167335

Erratum: Extremely tight binding of a ruthenium complex to glycogen synthase kinase 3 (ChemBioChem (2008) vol. 9 (2933-2936))
Atilla-Gokcumen, GE; Pagano, N; Streu, C; Maksimoska, J; Filippakopoulos, P; Knapp, S; Meggers, E;
ChemBioChem. 2009 10:198-. doi: 10.1002/cbic.200800489
PMID:

2008

Extremely tight binding of a ruthenium complex to glycogen synthase kinase 3.
Atilla-Gokcumen GE, Pagano N, Streu C, Maksimoska J, Filippakopoulos P, Knapp S, Meggers E
Chembiochem. 2008 9(18):2933-6. doi: 10.1002/cbic.200800489
PMID: 19035373

Structural coupling of SH2-kinase domains links Fes and Abl substrate recognition and kinase activation.
Filippakopoulos P, Kofler M, Hantschel O, Gish GD, Grebien F, Salah E, Neudecker P, Kay LE, Turk BE, Superti-Furga G, Pawson T, Knapp S
Cell. 2008 134(5):793-803. doi: 10.1016/j.cell.2008.07.047
PMID: 18775312

Similar biological activities of two isostructural ruthenium and osmium complexes.
Maksimoska J, Williams DS, Atilla-Gokcumen GE, Smalley KS, Carroll PJ, Webster RD, Filippakopoulos P, Knapp S, Herlyn M, Meggers E
Chemistry. 2008 14(16):4816-22. doi: 10.1002/chem.200800294
PMID: 18425743

2007

Structural and functional characterization of the human protein kinase ASK1.
Bunkoczi G, Salah E, Filippakopoulos P, Fedorov O, Müller S, Sobott F, Parker SA, Zhang H, Min W, Turk BE, Knapp S
Structure. 2007 15(10):1215-26. doi: 10.1016/j.str.2007.08.011
PMID: 17937911

Structural analysis identifies imidazo[1,2-b]pyridazines as PIM kinase inhibitors with in vitro antileukemic activity.
Pogacic V, Bullock AN, Fedorov O, Filippakopoulos P, Gasser C, Biondi A, Meyer-Monard S, Knapp S, Schwaller J
Cancer Res.. 2007 67(14):6916-24. doi: 10.1158/0008-5472.CAN-07-0320
PMID: 17638903

Crystal Structures of the p21-activated kinases PAK4, PAK5, and PAK6 reveal catalytic domain plasticity of active group II PAKs.
Eswaran J, Lee WH, Debreczeni JE, Filippakopoulos P, Turnbull A, Fedorov O, Deacon SW, Peterson JR, Knapp S
Structure. 2007 15(2):201-13. doi: 10.1016/j.str.2007.01.001
PMID: 17292838

2004

Crown-ether functionalized Co(III) sailicylideneimine complexes as ditopic carriers for the facilitated transport of zwitterions across a chloroform barrier.
Filippakopoulos, P; Coucouvanis, D;
ACS National Meeting Book of Abstracts. 2004 227:U1294-U1294. doi:
PMID:

1998

Cu<sup>II</sup>-herbicide complexes: Structure and bioactivity
Psomas, G; Dendrinou-Samara, C; Philippakopoulos, P; Tangoulis, V; Raptopoulou, CP; Samaras, E; Kessissoglou, DP;
Inorganica Chimica Acta. 1998 272:24-32. doi:
PMID:

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