Isocitrate Dehydrogenase 1 (IDH1)
Isocitrate dehydrogenase 1 (IDH1) EC:1.1.1.42 is one of three isocitrate dehydrogenase isoforms found in humans. Mutated IDH1 catalyzes α-KG to D-2-hydroxyglutarate (D2HG) and has been linked to tumorigenesis in certain types of cancers.
Isocitrate Dehydrogenase 1 (IDH1) Inhibitors |
|
|---|---|
| Cat. No. | Product Name / Activity |
| 7087 | AGI 5198 |
| Potent and selective inhibitor of mutant isocitrate dehydrogenase 1 (mIDH1) | |
| 7761 | Ivosidenib |
| Potent inhibitor of mutant isocitrate dehydrogenase (mIDH1) | |
Other |
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| Cat. No. | Product Name / Activity |
| 6124 | (R)-2-Hydroxyglutaric acid disodium salt |
| Oncometabolite produced by mutant isocitrate dehydrogenase | |
Isocitrate dehydrogenase 1 (IDH1) EC:1.1.1.42 is one of three isocitrate dehydrogenase isoforms found in humans. IDH1 and IDH2 are homodimeric enzymes found in the cytoplasm and mitochondria, respectively. In their wildtype form, they catalyze the conversion of isocitrate to α-ketoglutarate (α-KG), an essential intermediate in the Krebs cycle. IDH1 and IDH2 are structurally and functionally similar, but they differ substantially from IDH3 (an enzyme that plays a role in the Krebs cycle production of NADH).
In hypoxic cancer cells, or in those with defects in the electron transport chain, HIF-1 mediates signaling that upregulates PDK1 and Myc. This in turn drives IDH1-mediated reductive metabolism of glutamine, a process that is integral to lipogenesis in cancer cells. Genome sequencing projects have identified that mutations in IDH1 are linked to glioblastomas and acute myeloid leukemias (AML), as well as other cancers. Mutant IDH1 converts α-KG to D-2-hydroxyglutarate (D2HG) resulting in high intracellular levels of D2HG, which have been postulated to act as an oncometabolite, driving tumorigenesis. D2HG competitively blocks α-KG binding at a family of enzymes called 2-OG-dependent dioxygenases, which are regulators of important epigenetic events. Mutant IDH enzymes are strongly associated with hypermethylation of CpG islands in AML and glioblastomas. Furthermore, mutations in IDH1 switch the enzyme's function from NADPH production to NADPH catabolism, thus reducing the prevalence of a critical redox mediator.
External sources of pharmacological information for Isocitrate Dehydrogenase 1 (IDH1) :
Literature for Isocitrate Dehydrogenase 1 (IDH1)
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Our product guide reviews some of the main areas in cancer metabolism research and highlights products that can be used to explore metabolic pathways.
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Our Epigenetics review gives an overview of the development of chemical probes for epigenetic targets, and discusses their biological effects.
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Our Cancer Metabolism poster summarizes the main metabolic pathways in cancer cells, and highlights potential targets for cancer therapeutics.
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Our Epigenetics in Cancer poster summarizes the main epigenetic targets in cancer, and highlights chemical compounds for the inhibition of these targets.
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