Cancer Research UK is partnering with US biotech Ideaya Biosciences to develop small molecule inhibitors of Poly(ADP-ribose) glycohydrolase (PARG).
PARG is a cellular enzyme that breaks down Poly(ADP-ribose), which modulates protein function required for DNA repair.
Inhibition of PARG in cancer cells with highly-active PARP depletes cellular NAD, which is an essential factor of cellular respiration, resulting in “a dramatic decrease” in ATP (‘energy’) and ultimately cancer cell death.
“The Drug Discovery Unit at the Cancer Research UK Manchester Institute are delighted to be working alongside Ideaya to further develop our PARG inhibitor programme,” said Allan Jordan, head of chemistry in the Drug Discovery Unit.
“Stemming from fundamental biological discoveries made in our own Institute, PARG inhibitors offer a new way of compromising the ability of cancer cells to survive and resist treatment. We believe that these agents will offer a truly novel and clinically meaningful therapy for patients fighting against cancer.”
The collaboration “will accelerate the translation of discoveries from one of our major drug discovery units,” added Iain Foulkes, Cancer Research UK’s executive director of research and innovation.
Ideaya and Cancer Research UK said data from the PARG programme will be presented at the American Association of Cancer Research (AACR) Annual Meeting later this year.