2. Signaling Pathways
  3. Metabolic Enzyme/Protease
  4. Isocitrate Dehydrogenase (IDH)

Isocitrate Dehydrogenase (IDH)

Isocitrate Dehydrogenase (IDH)

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Isocitrate dehydrogenase (IDH), one of the key enzymes in the citric acid cycle, catalyzes the oxidative decarboxylation of isocitrate to alpha-ketoglutarate (α-KG) generating carbon dioxide and NADPH/NADH. IDHs belong to a large ancient family of enzymes that play central roles in energy metabolism, amino acid biosynthesis and vitamin production.

IDH protein family consists of three self-regulating enzymes (IDH1, IDH2, and IDH3). IDH1 and IDH2 are both nicotinamide adenine dinucleotide phosphate (NADP)-dependent enzymes that catalyze the oxidative decarboxylation of isocitrate to alpha-ketoglutarate (α-KG), while producing NADPH either in peroxisomes and the cytosol (IDH1) or in mitochondria (IDH2). IDH3 catalyzes the same reaction in the mitochondria, but in a NAD-dependent fashion. Mutations in IDH1 and IDH2 have been demonstrated in a variety of malignancies. IDH inhibitors have engendered hope in IDH1/2 mutant myeloid malignancies.

Isocitrate Dehydrogenase (IDH) Isoform Specific Products:

Isocitrate Dehydrogenase (IDH) Isoform Comparison
Cat. No. Product Name Effect Purity Chemical Structure
  • HY-112289B
    (1R)-IDH889
    		98.83%
    (1R)-IDH889 is the isomer of IDH889 (HY-112289), and can be used as an experimental control. IDH889 is an orally available, brain penetrant, allosteric and mutant specific inhibitor of isocitrate dehydrogenase 1 (IDH1). IDH889 has potent selectivity for IDH1 R132* mutations, with IC50s of 0.02 μM, 0.072 μM and 1.38 μM for IDH1R132H, IDH1R132C and IDH1wt, respectively. IDH889 shows potent cellular inhibition of R-2-hydroxyglutarate (2-HG) production with an IC50 of 0.014 μM.
    (1R)-IDH889
  • HY-143306
    IDH1 Inhibitor 5
    		Inhibitor
    IDH1 Inhibitor 5 (compound 2) is an IDH1 (isocitrate dehydrogenase 1) inhibitor. IDH1 Inhibitor 5 inhibits MOG cells and wild-type IDH1 glioma cells with expressing exogenous mutant IDH1 R132H protein with IC50s of 64.4 and 34.9 nM, respectively.
    IDH1 Inhibitor 5
  • HY-P2993C
    Isocitrate Dehydrogenase (NADP+), Bacteria
    Isocitrate Dehydrogenase (NADP+) , Bacteria (EC 1.1.1.42) is an enzyme that catalyzes the oxidative decarboxylation of isocitrate, producing alpha-ketoglutarate (α-ketoglutarate) and CO2.
    Isocitrate Dehydrogenase (NADP+), Bacteria
  • HY-158319
    Mutant IDH1/NAMPT-IN-1
    		Inhibitor
    Mutant IDH1/NAMPT-IN-1 (Compound 23h) is a dual inhibitor of mutant isocitrate dehydrogenase 1 (mutant IDH1) (IC50=14.93 nM) and nicotinamide phosphoribosyltransferase (NAMPT) (IC50=12.56 nM). Mutant IDH1/NAMPT-IN-1 can induce apoptosis. Mutant IDH1/NAMPT-IN-1 crosses the blood-brain barrier effectively.
    Mutant IDH1/NAMPT-IN-1
  • HY-156158
    IDH2R140Q-IN-2
    		Inhibitor
    IDH2R140Q-IN-2 (compound 36) is an an orally active IDH2R140Q inhibitor (IC50: 29 nM). IDH2R140Q-IN-2 reduces D2HG production in TF-1 cell lines expressing mutant IDH2R140Q (IC50: 10 nM). IDH2R140Q-IN-2 suppresses D2HG levels in tumor tissue. IDH2R140Q-IN-2 can be used for research of acute myeloid leukemia (AML).
    IDH2R140Q-IN-2
  • HY-162772
    IDH1/2-IN-1
    		Inhibitor
    IDH1/2-IN-1 (Compound 6b) serves as a dual inhibitor of IDH1(R132H)/IDH2(R140Q) with IC50 values of 0.22 μM and 1.6 μM, respectively. IDH1/2-IN-1 effectively inhibits tumor growth by suppressing tumor cell proliferation and enhancing host defense through the activation of antioxidant enzymes. Additionally, IDH1/2-IN-1 reduces inflammation and promotes apoptosis, demonstrating robust antitumor activity. IDH1/2-IN-1 holds potential for research in leukemia.
    IDH1/2-IN-1
  • HY-P2993A
    Isocitrate dehydrogenase, Microorganism
    Isocitrate dehydrogenase, Microorganism (IDH) (EC 1.1.1.42) is a citric acid or tricarboxylic acid cycle enzyme, is often used in biochemical studies. Isocitrate dehydrogenase catalyzes the oxidative decarboxylation of isocitrate to α-ketoglutarate and reduces NAD(P)+ to NAD(P)H, it plays important roles in cellular metabolism.
    Isocitrate dehydrogenase, Microorganism
  • HY-P2993D
    Isocitrate Dehydrogenase (NADP+), Yeast
    Isocitrate Dehydrogenase (NADP+) , Yeast (EC 1.1.1.42) is an enzyme that catalyzes the oxidative decarboxylation of isocitrate, producing alpha-ketoglutarate (α-ketoglutarate) and CO2.
    Isocitrate Dehydrogenase (NADP+), Yeast
  • HY-146002
    IDH2R140Q-IN-1
    		Inhibitor
    IDH2R140Q-IN-1 (compound C6) is a potent inhibitor of IDH2R140Q, with an IC50 of 6.1 nM. IDH2R140Q-IN-1 can be used for the research of acute myeloid leukemia.
    IDH2R140Q-IN-1
  • HY-149359
    IHMT-IDH1-053
    		Inhibitor
    IHMT-IDH1-053 (compound 16) is a highly selectivity and irreversible IDH1-mutant inhibitor with an IC50 of 4.7 nM for IDH1 R132H. IHMT-IDH1-053 displays high selectivity against IDH1 mutants over IDH1 wt and IDH2 wt/mutants. IHMT-IDH1-053 inhibits 2-hydroxyglutarate (2-HG) production in IDH1 R132H mutant transfected 293T cells (IC50=28 nM). IHMT-IDH1-053 binds to the IDH1 R132H protein in the allosteric pocket adjacent to the NAPDH binding pocket through a covalent bond with residue Cys269. IHMT-IDH1-053 inhibits the proliferation of HT1080 cell line and primary AML cells which both bear IDH1 R132 mutants.
    IHMT-IDH1-053
  • HY-18690S
    Enasidenib-d6
    		Inhibitor
    Enasidenib-d6 (AG-221-d6) is the deuterium labeled Enasidenib (HY-18690). Enasidenib is an oral, potent, reversible, selective inhibitor of the IDH2 mutant enzymes, with IC50s of 100 and 400 nM against IDH2R140Q and IDH2R172K, respectively.
    Enasidenib-d<sub>6</sub>
  • HY-136686
    IDH-C227
    		Inhibitor
    IDH-C227 is a potent and selective IDH1R132H inhibitor. IDH-C227 has anticancer effcts.
    IDH-C227
  • HY-174978
    SK60
    		Inhibitor
    SK60 is a dimethylated derivative of GSK321 (HY-18948) with low nanomolar potency and high selectivity for IDH1R132H (IC50 = 14.5 nM). SK60 can be used as a tracer for brain imaging with the fluorescent label [18F].
    SK60
  • HY-145743
    CP-17
    		Inhibitor
    CP-17 is a potent and selective IDH2/R140Q inhibitor with an IC50 of 40.75 nM. CP-17 exhibits excellent selectivity of >55-fold against the wild-type IDH2. CP-17 exhibits robust D-2-HG suppression activity in TF-1 (IDH2/R140Q) cells and reverses the cellular differentiation block induced by the R140Q mutation. CP-17 can be used for acute myeloid leukemia (AML) research.
    CP-17
  • HY-164542
    TQ05310
    		Inhibitor
    TQ05310 is an orally available inhibitor of IDH2 mutants, targeting both IDH2-R140Q (IC50=136.9 nM) and IDH2-R172K (IC50=37.9 nM) mutants. TQ05310 inhibits the production of 2-hydroxyglutarate (2-HG) and induces differentiation of cells expressing IDH2-R140Q and IDH2-R172K by inhibiting the enzymatic activity of mutant IDH2. TQ05310 can be used for the study of acute myeloid leukemia.
    TQ05310
  • HY-121916
    ML309
    		Inhibitor
    ML309 is a highly selective and potent inhibitor of the R132H mutant isocitrate dehydrogenase 1 (IDH1 R132H), with an IC50 of 96 nM. ML309 is a competitive inhibitor of α-KG, with a Ki value of 156 nM, and its inhibitory activity against the wild-type IDH1 is greater than 35 μM. ML309 effectively reduces the production of the tumor metabolite 2-HG in U87MG cells. ML309 can be used as a chemical probe to study the role of the mutant IDH1 in cancer.
    ML309
  • HY-123153
    GSK990
    		Control
    GSK990 is an inactive mutant IDH1 inhibitor with no significant inhibitory activity against wild-type or mutant IDH1/IDH2 enzymes. In experiments, GSK990 can serve as an inactive negative control for the IDH1 inhibitor GSK321 (HY-18948). GSK990 is applicable to the research of acute myeloid leukemia.
    GSK990
  • HY-P2993E
    Isocitrate dehydrogenase, Bacillus subtilis
    Isocitrate dehydrogenase, Bacillus subtilis (EC 1.1.1.42) is an enzyme that catalyzes the oxidative decarboxylation of isocitrate, producing alpha-ketoglutarate (α-ketoglutarate) and CO2.
    Isocitrate dehydrogenase, Bacillus subtilis
  • HY-124698
    MRK-A
    		Inhibitor
    MRK-A is a selective, blood-brain-barrier permeable mutant IDH1 inhibitor with an IC50 value of 5 nM. MRK-A inhibits 2-HG production. MRK-A has anti-cancer activity against brain tumors.
    MRK-A
  • HY-143234
    mIDH1-IN-1
    		Inhibitor
    mIDH1-IN-1 (compound 43) is a potent and selective mIDH1 (mutant isocitrate dehydrogenases 1) inhibitor, with an IC50 of 961.5 nM. mIDH1-IN-1 potently inhibits intracellular 2-HG (2-hydroxyglutarate) production in HT1080 cells, with an EC50 of 208.6 ± 8.0 nM. mIDH1-IN-1 shows a significant anti-proliferation activity on IDH1 mutant-U-87 cells, with an IC50 of 41.8 nM. mIDH1-IN-1 is an antitumor agent, and can be used for IDH1 mutated solid tumors research.
    mIDH1-IN-1
Cat. No. Product Name / Synonyms Application Reactivity
Isocitrate Dehydrogenase (IDH) Isoform Comparison

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