Discovery and development of small molecule antagonists of pleckstrin homology domains for the treatment of cancer. (360G-Wellcome-081759_Z_06_C)

Professor Jeremy Tavare and colleagues at the University of Bristol have been funded to optimise small molecules that inhibit intracellular "signal transduction" systems that become hyperactive in tumour cells. The protein kinase B (PKB/Akt) signalling pathway has been shown to play a central role in the development of numerous different human tumours and has led to intense interest by the pharmaceutical industry to identified inhibitors. However, rather than target the ATP-binding pocket of the kinase domain, Professor Tavares group alternative approach is inhibit the PH domain-mediated responses of PKB. Targeting such PH domain of proteins represents a new approach to drug discovery. If successful, it would become more generically applicable to other targets possessing PH domains that have a range of different biological activities and therapeutic relevance.