IDH1 and IDH2 are enzymes in the Krebs Cycle of glucose metabolism – IDH1 (AG-120) is active in the cyotplasm and IDH2 (AG-221) is active in the mitochondria.  Phase 1 clinical studies of these compounds are underway.

Mutated forms of these enzymes are seen in hematological malignancies, and sold tumors, notably AML.  The metabolite produced by the mutated enzymes, 2HG (2-hydroxyglutarate), cause epigenetic changes that block the normal differentiation of cells, which prevents them from entering the post-mitotic state, which leads to cancer.  Thus, 2HG is an “oncometabolite.”  (See http://www.agios.com/pipeline-idh.php)

As reported at the 2014 ASCO meeting, 6 of 7 patients in the Phase 1 study of AG-221 had objective responses.

Celgene, a leading oncology company with a robust portfolio and pipeline of cancer treatments, licensed the compounds. (see http://www.marketwatch.com/story/agios-pharmaceuticals-announces-that-celgene-exercised-its-option-to-license-ag-221-under-global-strategic-collaboration-2014-06-13)