NIH Research Festival
The mutated form of a key metabolic enzyme, isocitrate dehydrogenase (IDH), has emerged as a prominent oncology target given its prevalence in a diversity of cancers. The mutation of an active site arginine residue confers neomorphic activity to mutant isocitrate dehydrogenase (mIDH) and ultimately leads to the production of 2-hydroxyglutarate (2-HG), an oncometabolite which may be involved in the reprogramming of cells for tumorigenesis. In an effort to develop treatments for mIDH1 cancers, NCATS conducted a qHTS to identify inhibitors of both the R132H and the R132C IDH1 mutants. Subsequent medicinal chemistry optimization led to the discovery of potent inhibitors that minimize the production of 2-HG both in vitro and in vivo. Top compounds within this campaign continue to be interrogated in vivo in order to select a candidate for advancement into preclinical development.
Scientific Focus Area: Chemical Biology
This page was last updated on Friday, March 26, 2021