BioCentury
ARTICLE | Cover Story

Assaying 2-HG's function

March 7, 2013 8:00 AM UTC

Although 2-hydroxyglutarate is a known marker for various cancers, including leukemia,1,2 the metabolite's role in the disease remained unclear. Now, U.S. researchers have shown that the compound itself can drive leukemic transformation and that blocking its overproduction with a small molecule from Agios Pharmaceuticals Inc. reversed the effect.3

Isocitrate dehydrogenase 1 (IDH1) and IDH2 are critical metabolic enzymes that convert isocitrate to a-ketoglutarate, an essential cofactor for a number of enzymes. In 2009, Agios reported that a mutant form of IDH1 commonly found in gliomas gave the enzyme the additional ability to catalyze the formation of the (R) enantiomer of 2-hydroxyglutarate (2-HG) from a-ketoglutarate.4,5...