Current Progress in Isocitrate Dehydrogenase Mutations and Its Inhibitors in Gliomas / 中国药学杂志

ABSTRACT

Glioma is a primary brain tumor produced by canceration of the glial cells in the brain and spinal cord, accounting for 74.6% of the malignant tumors in the central nervous system. Isocitrate dehydrogenase (IDH) is the rate-limiting enzyme of the tricarboxylic acid cycle and catalyzes the oxidative decarboxylation of isocitrate to produce α-ketoglutarate (α-KG). Its mutant (mIDH) is a new point mutation, not only lose its original function but also gain new activity catalyzing the production of carcinogenic R-2-hydroxyglutarate (2HG) by α-KG. Isocitrate dehydrogenase inhibitors can reduce the production of 2HG and induce the demethylation of histones, thereby inhibiting tumor progression. Although discovered in 2008, the mIDH has become a tumor diagnostic marker and therapeutic target, mIDH2 and mIDH1 inhibitors for acute myeloid leukemia have been approved for marketing in 2017and 2018,respectively.For the treatment of acute myeloid leukemia, the reliability of isocitrate dehydrogenase mutants as tumor therapeutic targets was confirmed.At present, many pharmaceutical institutions around the world are conducting research and development of isocitrate dehydrogenase inhibitors.This article reviews the current research status of current IDH inhibitors.