Chemical inhibitors of Orai as possible therapeutics for treating colorectal cancer and associated liver metastases (360G-Wellcome-202025_Z_16_Z)

New drugs to treat colorectal and associated cancers are urgently required as Incidence of colorectal cancer alone is 75 thousand per year in the UK and there are no universally effective medications currently available. The project seeks to identify and develop new inhibitors of a protein (Orai3) as potential therapeutics for the treatment of these cancers and to support validation of these proteins as rational targets for future drug discovery. No chemical inhibitors of Orai3 have been discovered to date, however the group have recently identified a series of inhibitors of the homologue Orai1 with off-target activity at Orai3 which they hope to repurpose for Orai3 inhibition. The aim of the project is to develop a Structure and activity (SAR) for the inhibition of Orai3 channels thus allowing the control and inhibition of the Orai3 channel in cancerous cells. Chemical inhibitors identified within this project may offer potential starting points for development of commercially viable medicines and as tools to support the basic understanding of Orai related cancers leading to further research.