AGI-5198

These findings indicate the impact of ZMYND8 in the maintenance of genomic integrity and repair of IR-induced DNA damage in mIDH1 glioma.

Furthermore, class I HDAC inhibition sensitized chondrosarcoma to glutaminolysis and Bcl-2 family member inhibitors, suggesting that HDACs define the metabolic state and apoptotic threshold in chondrosarcoma. Taken together, HDAC inhibition may represent a promising targeted therapeutic strategy for chondrosarcoma patients, either as monotherapy or as part of combination treatment regimens.

3D culture is more relevant to IDH1 glioma biology. The importance of redox homeostasis in IDH1 glioma suggests that metabolic pathway(s) can be explored for therapeutic targeting, whereas IDH1 inhibitors may have counterproductive consequences in patient treatment.

Major metabolic adaptations involved pathways that can generate glutamate by using alternative substrates from glutamine, such as alanine or aspartate. Indeed, asparagine synthetase was upregulated both in vivo and in vitro revealing a new potential therapeutic target for a combinatory approach with CB839 against IDH1 gliomas.

inhibitor, AGI5198...To our knowledge, this is the first study that shows how altering the sphingolipid pathway in IDH1gliomas elucidates susceptibility that can arrest proliferation and initiate subsequent cellular death.