Development of Novel Therapeutics Targeting Isocitrate Dehydrogenase Mutations in Cancer.

Current Topics in Medicinal Chemistry
Horrick Sharma

Abstract

Isocitrate dehydrogenases 1 and 2 (IDH1 and IDH2) are key metabolic enzymes that catalyze the conversion of isocitrate to α-ketoglutarate (αKG). IDH1 and IDH2 regulate several cellular processes, including oxidative respiration, glutamine metabolism, lipogenesis, and cellular defense against oxidative damage. Mutations in IDH1 and IDH2 have recently been observed in multiple tumors, including gliomas, acute myeloid leukemia, myelodysplastic syndromes, and chondrosarcoma. IDH1 and IDH2 mutations involve a gain in neomorphic activity that catalyzes αKG conversion to (R)-2- hydroxyglutarate ((R)-2HG). IDH mutation-mediated accumulation of (R)-2HG results in epigenetic dysregulation, altered gene expression, and a block in cellular differentiation. Targeting mutant IDH by development of small molecule inhibitors is a rapidly emerging therapeutic approach as evidenced by the recent approval of the first selective mutant IDH2 inhibitor AG-221 (enasidenib) for the treatment of IDH2-mutated AML. This review will focus on mutant isocitrate dehydrogenase as a therapeutic drug target and provides an update on selective and pan-mutant IDH1/2 inhibitors in clinical trials and other mutant IDH inhibitors that are under development.

Citations

Aug 14, 2019·Journal of Molecular Cell Biology·Lichao LiuXiaohua Shen
Oct 21, 2019·Clinical & Translational Oncology : Official Publication of the Federation of Spanish Oncology Societies and of the National Cancer Institute of Mexico·M N AbbasH Cui
Jul 29, 2020·Blood Research·Silvia ParkHee-Je Kim
Oct 30, 2019·Biomarker Research·Xiaoyan Liu, Yuping Gong
Mar 8, 2019·Nature Medicine·Helai P MohammadCaretha L Creasy
Aug 30, 2020·Nature Communications·Neal K BennettKen Nakamura
Apr 2, 2020·Experimental Hematology & Oncology·Jifeng YuZhongxing Jiang
Apr 3, 2021·Cancer Treatment and Research Communications·Alessandro RizzoGiovanni Brandi
May 14, 2021·The FEBS Journal·Marton Siklos, Stefan Kubicek
Jul 17, 2021·Drug Discovery Today·Kate F ByrneGemma K Kinsella
Nov 5, 2020·Archives of Pathology & Laboratory Medicine·Calixto-Hope G LucasAndrew Horvai

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