A pinboard by
James O'Brien-Brown

PhD student, The University of Sydney


Synthesis of P2X7R antagonists in order to distinguish binding to orthosteric and allosteric sites

The P2X7 receptor (P2X7R) is believed to be a key mediator of inflammation in the brain (neuroinflammation) by releasing pro-inflammatory molecules such as interleukin 1-B (IL-1B). There has been substantial evidence linking high levels of IL-1B to neurodegenerative and neuropsychiatric diseases such as Alzheimer's disease, Parkinson's disease, and major depressive disorder.

There has been evidence in animal studies that shows inhibiting the action of the P2X7R prevents the release of IL-1B, and as a result, can prevent or hinder the progress of the aforementioned diseases.

No P2X7R antagonists have been successfully developed which can enter the brain in order to exert an anti-inflammatory (neuroprotective) effect, which is essential for the treatment of neurodegenerative diseases of the brain. By developing a P2X7R antagonist that can enter the brain, it will be possible to verify the conclusions drawn from animal studies that the P2X7R is an essential target for the prevention of such diseases.

My research focuses on determining the features of molecules required in order to bind to the P2X7R, and subsequently developing drug-like molecules which retain these features while using tactics of the medicinal chemist to allow entry of the molecule into the brain.