Agios scientists uncovered the function of the IDH1 mutation by employing novel techniques in a new area of cancer biology called cancer metabolism, which focuses on studying profound changes in metabolic activity in cancer cells. Through a mix of large-scale profiling of hundreds of cellular metabolites, x-ray crystallography, and innovative enzymology, the Agios team demonstrated that a single amino-acid substitution in the IDH1 active site allows the enzyme to acquire an entirely new activity to produce the metabolite 2HG. Analysis of tumor samples of brain cancer patients with the IDH1 mutation revealed up to hundred-fold elevations in concentrations of 2HG, a metabolite that has been previously linked to the formation of brain cancer.

Agios ™ founding principles included the belief that targeting important metabolic pathways of cancers could make a fundamental difference in the treatment of the disease. Our IDH1 discovery is a great example of the power of the team and of our approach in targeting cancer metabolic pathways. In just four months, scientists at Agios unraveled very complex biology to advance a new understanding of gliomas and the role of IDH1 and corresponding biomarkers, said David Schenkein, M.D., Chief Executive Officer, Agios. We are able to do this by utilizing a unique approach of integrating deep biology and leveraging our proprietary platform for cancer metabolism research.

We are looking forward to developing potential therapeutics specifically targeting IDH1 for patients with these devastating diseases, and to leveraging our unique cross functional approach to cancer metabolism research in order to discover insights into other targets and pathways, added Schenkein.

Source Agios Pharmaceuticals