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