vCardProf. Roger Griffin

Prof. Roger Griffin
Professor of Medicinal Chemistry

  • Email: r.j.griffin@ncl.ac.uk
  • Telephone: 0191 222 8591
  • Fax: 0191 222 8591
  • Address: Northern Institute for Cancer Research
    ADDI Laboratories
    School of Chemistry
    Bedson Building
    Newcastle University
    Newcastle upon Tyne
    NE1 7RU

Research Interests

The design, synthesis and biological evaluation of antitumour drugs acting on novel targets associated with the molecular pathology of cancer. The development of agents with the potential to synergise the antitumour activity of established drugs by modulating resistance processes (resistance modifying agents). The medicinal chemistry of antifolate drugs as antiproliferative and anti-infective agents.

ANTICANCER DRUG DISCOVERY
The Newcastle Anticancer Drug Discovery Initiative (ADDI) is a collaborative research programme between Professor B T Golding, Dr R J Griffin and Dr I R Hardcastle in the Department of Chemistry, and Professor A H Calvert, Professor D R Newell and Dr N J Curtin in the Cancer Research Unit of the Medical School. The programme was initiated in 1990 and currently comprises some twenty staff and postgraduate researchers. Research centres on the design, synthesis and biological evaluation of new antitumour agents, In addition to the development of compounds directed at targets identified from an understanding of the molecular pathology of cancer, the design of agents (resistance-modifiers) that potentiate the antitumour activity of existing drugs by modulating a resistance mechanism, is a major area of research interest.

Current Research Projects
The following drug discovery programmes are currently underway:

Small molecule Inhibitors of poly(ADP-ribose)polymerases (PARPs) to modulate DNA damage responses.
Novel pyrimidopyrimidines to modulate the cytotoxicity of antimetabolite drugs.
Crystal structure-based design of cyclin dependent kinase (CDK) inhibitors.
Design and synthesis of selective DNA-dependent protein kinase (DNA-PK) inhibitors.
Novel agents to disrupt p53-MDM2 interactions
Seclected Publications
T. G. Davies, J. Bentley, C. E. Arris, F. T. Boyle, N. J. Curtin, J. A. Endicott, A. E. Gibson, B. T. Golding, R. J. Griffin, I. R. Hardcastle, P. Jewsbury, L. N. Johnson, V. Mesguiche, D. R. Newell, M. E. M. Noble, J. A. Tucker, L. Z. Wang, and H. J. Whitfield. Structure-Based Design of a Potent Purine-Based Cyclin-Dependent Kinase Inhibitor. Nature Structural Biology, in press.
V. Mesguiche, R. J. Parsons, C. E. Arris, J. Bentley, F. T. Boyle, N. J. Curtin,T. G. Davies, J. A. Endicott, A. E. Gibson, B. T. Golding, R. J. Griffin, P. Jewsbury, L. N. Johnson, D. R. Newell, M. E. M. Noble, L. Z. Wang, and I. R. Hardcastle. 4-Alkoxy-2,6-diaminopyrimidine Derivatives: Inhibitors of Cyclin Dependent Kinases 1 and 2. Bioorg. Med. Chem. Lett. in press.
E. Gibson, C. E. Arris, J. Bentley, F. T. Boyle, N. J. Curtin, T. G. Davies, J. A. Endicott, B. T. Golding, S. Grant, R. J. Griffin, P. Jewsbury, L. N. Johnson, V. Mesguiche, D. R. Newell, M. E. M. Noble, J. A. Tucker, and H. J. Whitfield. Probing the ATP Ribose-Binding Domain of Cyclin-Dependent Kinases 1 and 2 with O6-Substituted Guanine Derivatives. J. Med. Chem. 2002, 45, 3381-3393.
J. S. Northen, F. T. Boyle, W. Clegg, N. J. Curtin, A. J. Edwards, R. J. Griffin and B. T. Golding. Controlled Stepwise Conversion of 2,4,6,8-Tetrachloropyrimido[5,4-d]pyrimidine into 2,4,6,8-Tetrasubstituted Pyrimido[5,4-d]pyrimidines. J. Chem. Soc. Perkin Trans. I, 2002, 108-115.
K. A. Croughton, C. S. Matthews, R. J. Griffin and M. F. G. Stevens. Investigations on the biological properties of the lipophilic DHFR-inhibitory benzoprims reveal non-folate modes of action and opportunities for anti-cancer drug design. Anti-cancer Drug Design, 2001, 16, 119-128.
M. L. Stockley, W. Clegg, G. Fontana, B. T. Golding, N. Martin, L. J. M. Rigoreau, G. C. M. Smith, and R. J. Griffin. Synthesis, Crystal Structure Determination, and Biological Properties of the DNA-Dependent Protein Kinase (DNA-PK) Inhibitor 3-cyano-6-hydrazonomethyl-5-(4-pyridyl)pyrid-[1H]-2-one (OK-1035). Bioorg. Med. Chem. Lett. 2001, 2837-2841.
P. G. Smith, H. D. Thomas, H. C. Barlow, R. J. Griffin, B. T. Golding, A. H. Calvert, D. R. Newell and N. J. Curtin. In vitro and in vivo properties of novel nucleoside transport inhibitors with improved pharmacological properties that potentiate antifolate activity. Clin. Cancer. Res., 2001, 7, 2105-2113.
W. White, R. Almassy, A. H. Calvert, N. J. Curtin, B. T. Golding, R. J. Griffin, K. Maegley, D. R. Newell and S. Srinivasan. Resistance-Modifying Agents. 9. Synthesis and Biological Properties of Benzimidazole Inhibitors of the DNA Repair Enzyme Poly(ADP-Ribose) Polymerase (PARP). J. Med. Chem., 2000, 43, 4084-4097.
Arris, F T. Boyle, A H. Calvert, N. J. Curtin, P. Jewsbury, J. A. Endicott, A. E. Gibson, B. T. Golding, R. J Griffin, L. N. Johnson, A. Laurie, N. K. Lembicz, D. R. Newell, M. E. M. Noble, E. Sausville and R. Schultz. O6-Substituted Guanines and 4-Substituted Pyrimidines: A Novel Class of Antiproliferative Cyclin Dependent Kinase Inhibitors with Distinct Molecular Interactions and Tumor Cell Growth Inhibition Profiles. J. Med. Chem., 2000, 43, 2797-2804.
R. J. Griffin, C. E. Arris, C. Bleasdale, F. T. Boyle, A. H. Calvert, N. J. Curtin, C. Dalby, B. T. Golding, S. Kanugula, N. K. Lembicz, D. R. Newell, and A. E. Pegg. Resistance-Modifying Agents. 8. Inhibition of O6-Alkylguanine-DNA Alkyltransferase by O6-Alkenyl-, O6-Cycloalkenyl- and O6-(2-Oxoalkyl)-guanines, and Potentiation of Temozolomide Cytotoxicity in vitro by O6-(1-Cyclopentenylmethyl)guanine. J. Med. Chem., 2000, 43, 4071-4083.

Selected Publications

Projects