Inhibitors of BFL-1

BFL-1 is a prosurvival protein that has recently been implicated in melanoma and in the development of resistance to some anti-cancer drugs. BH3 mimetic small molecule inhibitors target and neutralise prosurvival proteins and are currently being evaluated in clinical trials as anti-cancer therapies.

We are currently developing a robust, high capacity screening assay based on ALPHAScreen™ technology (PerkinElmer). This will be used to screen the WECC library with the ultimate aim of developing new compounds that can target BFL-1 specifically and with high affinity.

Inhibitors of apoptosis

This project is an ongoing collaboration with colleagues from multiple research divisions including the ACRF Chemical Biology division and the Cancer and Haematology division. It involves phenotypic screening using genetically engineered cell lines to identify inhibitors of apoptosis. We have also provided ongoing support to medicinal chemistry efforts to further increase potency of hit compounds that have come out of the screen.

This approach will enable researchers to develop tool molecules to further dissect the apoptotic signaling pathway. In addition, it has the potential to identify new therapeutic targets and open up new areas of disease biology. Potential therapeutic indications include conditions linked to excessive cellular apoptosis such as stroke, traumatic brain injury and neurodegenerative disease.