Panagis Filippakopoulos

Summary

Affiliation: University of Oxford
Country: UK

Publications

  1. doi request reprint The bromodomain interaction module
    Panagis Filippakopoulos
    Nuffield Department of Clinical Medicine, Structural Genomics Consortium, University of Oxford, Old Road Campus Research Building, Roosevelt Drive, Oxford OX3 7LD, UK
    FEBS Lett 586:2692-704. 2012
  2. pmc Histone recognition and large-scale structural analysis of the human bromodomain family
    Panagis Filippakopoulos
    Nuffield Department of Clinical Medicine, Structural Genomics Consortium, University of Oxford, Old Road Campus Research Building, Roosevelt Drive, Oxford OX3 7LD, UK
    Cell 149:214-31. 2012
  3. pmc 3,5-dimethylisoxazoles act as acetyl-lysine-mimetic bromodomain ligands
    David S Hewings
    Nuffield Department of Clinical Medicine, Structural Genomics Consortium, University of Oxford, Old Road Campus Research Building, Roosevelt Drive, Oxford OX3 7DQ, U K
    J Med Chem 54:6761-70. 2011
  4. pmc Optimization of 3,5-dimethylisoxazole derivatives as potent bromodomain ligands
    David S Hewings
    Department of Chemistry, Chemistry Research Laboratory, University of Oxford, Mansfield Road, Oxford, OX1 3TA, UK
    J Med Chem 56:3217-27. 2013
  5. pmc RVX-208, an inhibitor of BET transcriptional regulators with selectivity for the second bromodomain
    Sarah Picaud
    Structural Genomics Consortium, Nuffield Department of Clinical Medicine, University of Oxford, Oxford OX3 7DQ, United Kingdom
    Proc Natl Acad Sci U S A 110:19754-9. 2013
  6. pmc Structures of Down syndrome kinases, DYRKs, reveal mechanisms of kinase activation and substrate recognition
    Meera Soundararajan
    Structural Genomics Consortium, Nuffield Department of Clinical Medicine, University of Oxford, Old Road Campus, Roosevelt Drive, Oxford OX3 7DQ, UK
    Structure 21:986-96. 2013
  7. pmc PFI-1, a highly selective protein interaction inhibitor, targeting BET Bromodomains
    Sarah Picaud
    Structural Genomics Consortium and Target Discovery Institute, Nuffield Department of Clinical Medicine, University of Oxford, Oxford, USA
    Cancer Res 73:3336-46. 2013
  8. pmc Selective inhibition of BET bromodomains
    Panagis Filippakopoulos
    Department of Clinical Medicine, Structural Genomics Consortium, University of Oxford, Old Road Campus, Roosevelt Drive, Oxford OX3 7DQ, UK
    Nature 468:1067-73. 2010
  9. pmc Large-scale structural analysis of the classical human protein tyrosine phosphatome
    Alastair J Barr
    University of Oxford, Structural Genomics Consortium, Old Road Campus Research Building, Roosevelt Drive, Headington, Oxford, OX3 7DQ, UK
    Cell 136:352-63. 2009
  10. doi request reprint Bromodomain-peptide displacement assays for interactome mapping and inhibitor discovery
    Martin Philpott
    Structural Genomics Consortium, University of Oxford, Oxford OX3 7DQ, UK
    Mol Biosyst 7:2899-908. 2011

Collaborators

Detail Information

Publications21

  1. doi request reprint The bromodomain interaction module
    Panagis Filippakopoulos
    Nuffield Department of Clinical Medicine, Structural Genomics Consortium, University of Oxford, Old Road Campus Research Building, Roosevelt Drive, Oxford OX3 7LD, UK
    FEBS Lett 586:2692-704. 2012
    ..This review provides an overview over sequence requirements of BRDs, known substrates and the structural mechanisms of specific K(ac) recognition...
  2. pmc Histone recognition and large-scale structural analysis of the human bromodomain family
    Panagis Filippakopoulos
    Nuffield Department of Clinical Medicine, Structural Genomics Consortium, University of Oxford, Old Road Campus Research Building, Roosevelt Drive, Oxford OX3 7LD, UK
    Cell 149:214-31. 2012
    ..These data provide a foundation for structure-based drug design of specific inhibitors for this emerging target family...
  3. pmc 3,5-dimethylisoxazoles act as acetyl-lysine-mimetic bromodomain ligands
    David S Hewings
    Nuffield Department of Clinical Medicine, Structural Genomics Consortium, University of Oxford, Old Road Campus Research Building, Roosevelt Drive, Oxford OX3 7DQ, U K
    J Med Chem 54:6761-70. 2011
    ..These compounds are promising leads for the further development of selective probes for the bromodomain and extra C-terminal domain (BET) family and CREBBP bromodomains...
  4. pmc Optimization of 3,5-dimethylisoxazole derivatives as potent bromodomain ligands
    David S Hewings
    Department of Chemistry, Chemistry Research Laboratory, University of Oxford, Mansfield Road, Oxford, OX1 3TA, UK
    J Med Chem 56:3217-27. 2013
    ....
  5. pmc RVX-208, an inhibitor of BET transcriptional regulators with selectivity for the second bromodomain
    Sarah Picaud
    Structural Genomics Consortium, Nuffield Department of Clinical Medicine, University of Oxford, Oxford OX3 7DQ, United Kingdom
    Proc Natl Acad Sci U S A 110:19754-9. 2013
    ..Our data demonstrate the feasibility of specific targeting within the BET family resulting in different transcriptional outcomes and highlight the importance of BD1 in transcriptional regulation. ..
  6. pmc Structures of Down syndrome kinases, DYRKs, reveal mechanisms of kinase activation and substrate recognition
    Meera Soundararajan
    Structural Genomics Consortium, Nuffield Department of Clinical Medicine, University of Oxford, Old Road Campus, Roosevelt Drive, Oxford OX3 7DQ, UK
    Structure 21:986-96. 2013
    ..Our data also show that DYRK1A wild-type and Y321F mutant retain tyrosine autophosphorylation activity...
  7. pmc PFI-1, a highly selective protein interaction inhibitor, targeting BET Bromodomains
    Sarah Picaud
    Structural Genomics Consortium and Target Discovery Institute, Nuffield Department of Clinical Medicine, University of Oxford, Oxford, USA
    Cancer Res 73:3336-46. 2013
    ....
  8. pmc Selective inhibition of BET bromodomains
    Panagis Filippakopoulos
    Department of Clinical Medicine, Structural Genomics Consortium, University of Oxford, Old Road Campus, Roosevelt Drive, Oxford OX3 7DQ, UK
    Nature 468:1067-73. 2010
    ..These data establish proof-of-concept for targeting protein-protein interactions of epigenetic 'readers', and provide a versatile chemical scaffold for the development of chemical probes more broadly throughout the bromodomain family...
  9. pmc Large-scale structural analysis of the classical human protein tyrosine phosphatome
    Alastair J Barr
    University of Oxford, Structural Genomics Consortium, Old Road Campus Research Building, Roosevelt Drive, Headington, Oxford, OX3 7DQ, UK
    Cell 136:352-63. 2009
    ..This phosphatome resource gives an expanded insight into intrafamily PTP diversity, catalytic activity, substrate recognition, and autoregulatory self-association...
  10. doi request reprint Bromodomain-peptide displacement assays for interactome mapping and inhibitor discovery
    Martin Philpott
    Structural Genomics Consortium, University of Oxford, Oxford OX3 7DQ, UK
    Mol Biosyst 7:2899-908. 2011
    ..This assay methodology is thereby anticipated to provide the basis both for broader interactome profiling and for small molecule inhibitor discovery...
  11. pmc Structural basis for Par-4 recognition by the SPRY domain- and SOCS box-containing proteins SPSB1, SPSB2, and SPSB4
    Panagis Filippakopoulos
    Structural Genomics Consortium, University of Oxford, Old Road Campus, Roosevelt Drive, Oxford OX3 7DQ, UK
    J Mol Biol 401:389-402. 2010
    ..These structural changes limit high-affinity interactions for SPSB2 to aspartate-containing sequences, whereas SPSB1 and SPSB4 bind strongly to both Par-4 and VASA peptides...
  12. pmc Structure and functional characterization of the atypical human kinase haspin
    Jeyanthy Eswaran
    Structural Genomics Consortium, Nuffield Department of Medicine, University of Oxford, Oxford OX3 7DQ, United Kingdom
    Proc Natl Acad Sci U S A 106:20198-203. 2009
    ....
  13. doi request reprint Benzodiazepines and benzotriazepines as protein interaction inhibitors targeting bromodomains of the BET family
    Panagis Filippakopoulos
    University of Oxford, Nuffield Department of Clinical Medicine, Structural Genomics Consortium, Old Road Campus Research Building, Roosevelt Drive, Oxford OX3 7LD, UK
    Bioorg Med Chem 20:1878-86. 2012
    ..Our analysis revealed the importance of the 1-methyl triazolo ring system for BET binding and suggests modifications for the development of further high affinity bromodomain inhibitors...
  14. doi request reprint [1,2,4]Triazolo[4,3-a]phthalazines: Inhibitors of Diverse Bromodomains
    Oleg Fedorov
    Structural Genomics Consortium, Nuffield Department of Medicine, University of Oxford, Old Road Campus Research Building, Roosevelt Drive, Oxford OX3 7DQ, U K
    J Med Chem 57:462-76. 2014
    ..The compounds described are valuable starting points for discovery of selective bromodomain inhibitors and inhibitors with mixed bromodomain pharmacology. ..
  15. pmc Specific CLK inhibitors from a novel chemotype for regulation of alternative splicing
    Oleg Fedorov
    University of Oxford, Nuffield Department of Clinical Medicine, Structural Genomics Consortium, Old Road Campus Research Building, Oxford OX37DQ, UK
    Chem Biol 18:67-76. 2011
    ....
  16. pmc Bromodomains as therapeutic targets
    Susanne Muller
    Department of Clinical Medicine, Structural Genomics Consortium, University of Oxford, Oxford, UK
    Expert Rev Mol Med 13:e29. 2011
    ..It is likely that BRDs will emerge alongside HATs and HDACs as interesting targets for drug development for the large number of diseases that are caused by aberrant acetylation of lysine residues...
  17. pmc Structural coupling of SH2-kinase domains links Fes and Abl substrate recognition and kinase activation
    Panagis Filippakopoulos
    Structural Genomics Consortium, University of Oxford, Old Road Campus, Roosevelt Drive, Oxford OX3 7DQ, UK
    Cell 134:793-803. 2008
    ..Thus, the SH2 and catalytic domains of active Fes and Abl pro-oncogenic kinases form integrated structures essential for effective tyrosine kinase signaling...
  18. pmc Structural and functional characterization of the human protein kinase ASK1
    Gabor Bunkoczi
    University of Oxford, Structural Genomics Consortium, Botnar Research Centre, Oxford OX3 7LD, United Kingdom
    Structure 15:1215-26. 2007
    ..The determined high-resolution structure of ASK1 and identified ATP mimetic inhibitors will provide a first starting point for the further development of selective inhibitors...
  19. pmc SH2 domains: modulators of nonreceptor tyrosine kinase activity
    Panagis Filippakopoulos
    Structural Genomics Consortium, University of Oxford, Old Road Campus Research Building, Roosevelt Drive, Headington, Oxford OX3 7DQ, UK
    Curr Opin Struct Biol 19:643-9. 2009
    ..Here we summarize our understanding of mechanisms that lead to tyrosine kinase activation by direct interactions mediated by the SH2 domain and discuss how mutations in the SH2 domain trigger kinase inactivation...
  20. pmc Crystal Structures of the p21-activated kinases PAK4, PAK5, and PAK6 reveal catalytic domain plasticity of active group II PAKs
    Jeyanthy Eswaran
    University of Oxford, Structural Genomics Consortium, Botnar Research Centre, Oxford OX3 7LD, United Kingdom
    Structure 15:201-13. 2007
    ..Inhibitor screening identified six potent PAK inhibitors from which a tri-substituted purine inhibitor was cocrystallized with PAK4 and PAK5...
  21. doi request reprint The crystal structure of human GLRX5: iron-sulfur cluster co-ordination, tetrameric assembly and monomer activity
    Catrine Johansson
    University of Oxford, UK
    Biochem J 433:303-11. 2011
    ..Apo-GLRX5 reduced glutathione mixed disulfides with a rate 100 times lower than did GLRX2 and was active as a glutathione-dependent electron donor for mammalian ribonucleotide reductase...