GPR55 Antagonists

Our drug discovery programme has identified a number of novel classes of compounds which act as selective antagonists at the GPR55 receptor and are developing these as treatments for metastatic breast cancer and neuropathic pain.

GPR55 is a G protein coupled receptor that is over-expressed on the most aggressive, highly metastatic breast tumour cells; blocking GPR55 prevents cell invasion and migration. We have filed a patent application on the use of GPR55 as a predictive biomarker for aggressive breast cancer, and are following this up with the development of selective GPR55 antagonists as therapeutic agents for tumours shown to express this biomarker. Such compounds would have potential as novel, non-cytotoxic selective agents for the attenuation of breast cancer metastasis, and would be an invaluable addition to our therapeutic arsenal.

The potential for GPR55 modulators as therapeutics for pain has been described in the literature; our studies will allow this therapeutic potential to be assessed.

Early studies have shown that agonists of the GPR55 receptor stimulate migration of human breast cancer cell lines, while antagonists inhibit migration of these cells toward a chemo-attractant. This is regarded as a highly informative model for how rapidly the cancer will spread, and provides strong evidence that antagonists will be of major therapeutic value in preventing the spread of breast cancer.

Review: Ross, RA (2009). The enigmatic pharmacology of GPR55. Trends in Pharmacological Sciences. 30(3):156-63

Funding: North East Scotland Technology Seed Fund, SULSA, Roemex Ltd, Canadian Institutes of Health Research

Project Team: Professor Ruth Ross, Dr Iain Greig

SULSA