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
Selected Publications
- Thomas HD; Saravanan K; Wang LZ; Lin MJ; Northen JS; Barlow H; Barton M; Newell DR; Griffin RJ; Golding BT; Curtin NJ. Preclinical evaluation of a novel pyrimidopyrimidine for the prevention of nucleoside and nucleobase reversal of antifolate cytotoxicity. Molecular Cancer Therapeutics 2009, 8(7), 1828-1837.
- Murr M; Smith G; Griffin R; Cano C; Golding BT; Hardcastle IR; Hummersome M; Frigerio M; Curtin NJ; Menear K; Richardson C. 8-Biarylchromen-4-one inhibitors of the DNA-dependent protein kinase (DNA-PK). Bioorganic and Medicinal Chemistry Letters 2008, 18(17), 4885-4890.
- Riedinger C; Endicott JA; Kemp SJ; Smyth LA; Watson A; Valeur E; Golding BT; Griffin RJ; Hardcastle IR; Noble ME; McDonnell JM. Analysis of Chemical Shift Changes Reveals the Binding Modes of Isoindolinone Inhibitors of the MDM2-p53 Interaction. Journal of the American Chemical Society 2008, 130(47), 16038-16044.
- Willmore E; Elliott SL; Mainou-Fowler T; Summerfield GP; Jackson GH; O'Neill F; Lowe C; Carter A; Harris R; Pettitt AR; Cano-Soumillac C; Griffin RJ; Cowell IG; Austin CA; Durkacz BW. DNA-dependent protein kinase is a therapeutic target and an indicator of poor prognosis in B-cell chronic lymphocytic leukemia. Clinical Cancer Research 2008, 14(12), 3984-3992.
- Lu X; Liu J; Watson A; Hardcastle IR; Griffin RJ; Golding BT; Newell DR; Lunec J. MDM2 and MDMX status as a determinant of in vitro cellular sensitivity to MDM2 antagonists in human tumour cell lines. EJC Supplements 2008, 6(12), 137.
- Seeberger S; Griffin RJ; Hardcastle IR; Golding BT. A new strategy for the synthesis of taurine derivatives using the 'safety-catch' principle for the protection of sulfonic acids. Organic & Biomolecular Chemistry 2007, 5(1), 132-138.