GNE-317

GNE-317 is a potent, small-molecule dual inhibitor of phosphoinositide 3-kinase (PI3K) and mammalian target of rapamycin (mTOR). Developed by Genentech, it was specifically engineered as a brain-penetrant derivative of GDC-0980 (apitolisib) by incorporating an oxetane moiety to reduce its affinity for efflux transporters such as P-glycoprotein (P-gp) and Breast Cancer Resistance Protein (BCRP). This structural modification allows GNE-317 to effectively cross the blood-brain barrier, a significant challenge for many PI3K inhibitors. Preclinical studies have demonstrated that GNE-317 provides significant tumor growth inhibition and survival benefits in orthotopic models of glioblastoma multiforme (GBM), particularly in PTEN-deficient settings. It is currently utilized as a research tool to study intracranial malignancies and PI3K/mTOR pathway signaling in the central nervous system.

Other names

5-[6-(3-methoxyoxetan-3-yl)-7-methyl-4-(morpholin-4-yl)thieno[3,2-d]pyrimidin-2-yl]pyrimidin-2-amineCAS 1394076-92-6CAS1394076-92-6CAS-1394076-92-6