IDH1
IDH1 (isocitrate dehydrogenase 1) is a cytosolic and peroxisomal NADP+-dependent enzyme that catalyzes the conversion of isocitrate to α-ketoglutarate (α-KG) while generating NADPH, thereby supporting cellular redox homeostasis and intermediary metabolism[1][2]. Mechanistically, IDH1 contributes to metabolic pathways that regulate oxidative stress responses, biosynthetic processes, and α-KG availability for multiple cellular reactions[1][2]. In cancer biology, IDH1 is notable because recurrent mutations, most commonly affecting residue R132, confer a neomorphic enzymatic activity that converts α-KG into D-2-hydroxyglutarate (D-2HG), an oncometabolite that accumulates in tumor cells[3][2][4]. Elevated D-2HG inhibits α-KG-dependent dioxygenases, resulting in widespread epigenetic alterations and impaired cellular differentiation that contribute to tumor development and progression[2][4][5]. These molecular effects have been extensively studied in glioma and acute myeloid leukemia models, where mutant IDH1 functions as an early driver of tumorigenesis and metabolic reprogramming[4][5][6]. Compared with the related isoform IDH2, which is localized primarily in mitochondria, IDH1 is predominantly cytosolic and peroxisomal, creating distinct subcellular metabolic functions despite sharing similar catalytic chemistry[1][7]. For experimental applications, selective mutant IDH1 inhibitors reduce D-2HG production and promote cellular differentiation in preclinical models, making them valuable tools for investigating IDH1-dependent metabolic and epigenetic mechanisms in cancer research[5][6][8].
References:
- [1]. IDH1 gene information from NCBI.
- [2]. Alzial G, et al. Wild-type isocitrate dehydrogenase under the spotlight in glioblastoma. Oncogene. 2022 Jan;41(5):613-621. [Content Brief]
- [3]. Liu Z, et al. Inhibition of cancer-associated mutant isocitrate dehydrogenases: synthesis, structure-activity relationship, and selective antitumor activity. J Med Chem. 2014 Oct 23;57(20):8307-18. [Content Brief]
- [4]. Waitkus MS, et al. Biological Role and Therapeutic Potential of IDH Mutations in Cancer. Cancer Cell. 2018 Aug 13;34(2):186-195. [Content Brief]
- [5]. Rohle D, et al. An inhibitor of mutant IDH1 delays growth and promotes differentiation of glioma cells. Science. 2013 May 3;340(6132):626-30. [Content Brief]
- [6]. Golub D, et al. Mutant Isocitrate Dehydrogenase Inhibitors as Targeted Cancer Therapeutics. Front Oncol. 2019 May 17;9:417. [Content Brief]
- [7]. Al-Khallaf H. Isocitrate dehydrogenases in physiology and cancer: biochemical and molecular insight. Cell Biosci. 2017;7:37.
- [8]. Popovici-Muller J, et al. Discovery of the First Potent Inhibitors of Mutant IDH1 That Lower Tumor 2-HG in Vivo. ACS Med Chem Lett. 2012 Sep 17;3(10):850-5. [Content Brief]
All Product Categories
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IDH1 Related Products (27)
Related Products (27)
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Antibodies (1)
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ML309
0 ImagesCat. No.: HY-121916CAS No.: 1355446-05-7ML309 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.
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Mutant IDH1-IN-7
0 ImagesCat. No.: HY-175213Mutant IDH1-IN-7 is a highly selective Isocitrate Dehydrogenase 1 (IDH1) R132H (IC50 = 0.26 μM, Kd = 2.1 μM)/R132C (IC50 = 1.1 μM) inhibitor. Mutant IDH1-IN-7 has no inhibitory effect on wild-type IDH1, IDH2-wt, and IDH2 R140Q. Mutant IDH1-IN-7 inhibits 2-Hydroxyglutarate (2-HG) production in U87-MG R132H cells (EC50 = 0.55 μM). Mutant IDH1-IN-7 exhibits moderate antiproliferative effects on U87-MG R132H and HT-1080 cells.
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BRD2879
0 ImagesCat. No.: HY-120765CAS No.: 1304750-47-7BRD2879 is a potent IDH1-R132H inhibitor with IC50 values of 0.05, 2.5, >20, >20 µM for IDH1-R132H, IDH1-R132C, IDH1-WT, IDH2-R140Q, respectively. BRD2879 reduces (R)-2-hydroxyglutarate (R-2HG) levels.
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IDH1 Inhibitor 9
0 ImagesCat. No.: HY-162631CAS No.: 3037967-71-5IDH1 Inhibitor 9 (compound 11S) is a potent IDH1 inhibitor with IC50 values of 124.4, 95.7 nM for IDH1 R132H, IDH1 R132C, respectively. IDH1 Inhibitor 9 induces apoptosis and cell cycle arrest at the S phase. IDH1 Inhibitor 9 shows anti-tumor activity.
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mIDH1-IN-2
0 ImagesCat. No.: HY-175770mIDH1-IN-2 is a brain-penetrant isocitrate dehydrogenase 1 (IDH1) inhibitor. mIDH1-IN-2 shows subnanomolar potency against IDH1 R132H and R132C (IC50 = 80.0 and 58.0 nM) and minimal activity against wt-IDH1/2. mIDH1-IN-2 also inhibits PDK1 (IC50 = 0.61 μM) and reduces PDH phosphorylation dose-dependently. mIDH1-IN-2 can inhibit cells proliferation, induces S phase arrest and promotes apoptosis. mIDH1-IN-2 can be used for the research of cancer, such as glioma.
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Mutant IDH1-IN-3
0 ImagesCat. No.: HY-100476CAS No.: 1648909-73-2Mutant IDH1-IN-3 (Compound 1) is a selective allosteric inhibitor of mutant isocitrate dehydrogenase 1 (IDH1). Mutant IDH1-IN-3 has an IC50 of 13 nM for R132H IDH1. Mutant IDH1-IN-3 inhibits the production of D-2-hydroxyglutaric acid (2HG) in cells. Mutant IDH1-IN-3 can be used in the study of cancer.
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Crelosidenib gentisate
0 ImagesCat. No.: HY-131312ACAS No.: 2759438-85-0Synonyms: LY3410738 gentisate; Mutant IDH1-IN-6 gentisateCrelosidenib (gentisate) is a potent, selective and orally active mutant isocitrate dehydrogenase (IDH) inhibitor with IC50 of 6.27 nM, 3.71 nM, 36.9 nM and 11.5 nM for IDH1 R132H, IDH1 R132C, IDH2 R140Q and IDH2 R172K mutant enzymes, respectively. Crelosidenib (gentisate) is less active at inhibiting the IDH wild-type enzymes.
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