idh

IHMT-IDH1-053 (compound 16) is an irreversible inhibitor highly selective for the IDH1 R132H mutant, with an IC50 of 4.7 nM. It preferentially targets IDH1 mutants over wild-type IDH1 and IDH2, in both their wild-type and mutant forms. In 293T cells transfected with the IDH1 R132H mutant, IHMT-IDH1-053 reduces 2-hydroxyglutarate (2-HG) production with an IC50 of 28 nM. The compound binds to the R132H protein at an allosteric site near the NADPH binding region, forming a covalent linkage with Cys269. Additionally, IHMT-IDH1-053 inhibits the growth of both the HT1080 cell line and primary acute myeloid leukemia (AML) cells harboring IDH1 R132 mutations [1].

Enasidenib (AG-221) is an orally available inhibitor of specific mutant forms of the mitochondrial enzyme isocitrate dehydrogenase type 2 (IDH2), with potential antineoplastic activity.

Alternaphenol B2, a selective inhibitor of mutant isocitrate dehydrogenase 1 (IDH1m), is sourced from the coral-derived fungus Parengyodontium album SCSIO SX7W11. It exhibits inhibitory activity specifically against the IDH1 R132H mutation, with an IC50 of 41.9 μM [1].

Vorasidenib (PVM MA) is an inhibitor of mutant isocitrate dehydrogenase (IDH; IC50s = 31.9 and 31.7 nM for IDH1R132H and IDH2R140Q, respectively)

IDH-305 is an orally available, mutation-selective, and brain-penetrant IDH1 inhibitor targeting the IDH1 (R132) mutation. It is 200-fold more selective for mutant IDH1 isoforms than wild type, with IC50s of 27 nM, 28 nM, and 6.14 nM for IDH1R132H, IDH1R132C, and IDH1WT, respectively.

IDH-C227 is a selective and potent inhibitor of IDH1R132H that exhibits anticancer activity.

Mutant IDH1-IN-2 is an inhibitor of mutant Isocitrate dehydrogenase (IDH) proteins, with an IC50 of 16.6 nM in fluorescence biochemical assay and an IC50 of <22 nM in LS-MS biochemical assay.

IDH2R140Q-IN-2 is an orally active and potent IDH2R140Q inhibitor with an IC50 of 29 nM.IDH2R140Q-IN-2 possesses potential antitumour activity, reducing D2HG production in TF-1 cell lines carrying the IDH2R140Q mutation (IC50 of 10 nM) and inhibiting tumour tissue D2HG levels.IDH2R140Q-IN-2 is suitable for the study of acute myeloid leukaemia (AML).

Mutant IDH1-IN-1 is a potent inhibitor of the mutant IDH1 R132 h, exhibiting an IC50 of less than 0.1 μM.

Mutant IDH1 inhibitor is an effective inhibitor of mutant IDH1 R132H (IC50: < 72 nM).

IDH1 Inhibitor 2 (compound 13) is a potent IDH1 inhibitor through direct covalent modification of His315, with an IC50 of 110 nM.

IDH1 Inhibitor 3 is a mutant isocitric dehydrogenase 1 (IDH1) inhibitor (IC50: 45 nM for IDH1R132H).

Mutant IDH1-IN-4 is an mutant Isocitrate dehydrogenase 1 (IDH 1) inhibitor.

IDH889 is a brain penetrant, an allosteric and mutant specific IDH1 inhibitor. IDH889 has effective selectivity for IDH1 R132* mutations (IC50s: 0.02 μM, 0.072 μM, and 1.38 μM for IDH1R132H, IDH1R132C, and IDH1wt).

IDH1 Inhibitor 1 is an orally bioavailable, brain-penetrant, and selective mutant IDH1 inhibitor (IC50s: 0.021 μM, 0.045 μM, and 2.52 μM for IDH1R132H, IDH1R132C, and IDH1WT).

Mutant IDH1-IN-6 is an orally active compound that effectively inhibits mutant isocitrate dehydrogenase (IDH) enzymes. It demonstrates potency and selectivity, with IC50 values of 6.27, 3.71, 36.9, and 11.5 nM for IDH1 R132H, IDH1 R132C, IDH2 R140Q, and IDH2 R172K mutants, respectively. Notably, Mutant IDH1-IN-6 exhibits lower activity in inhibiting wild-type IDH enzymes.

IDH1 2-IN-1 (Compound 6b) is a dual inhibitor of IDH1(R132H) IDH2(R140Q) with IC50 values of 0.22 μM and 1.6 μM, respectively. This compound effectively inhibits tumor growth by suppressing tumor cell proliferation and activating antioxidative enzymes to enhance host defense. Additionally, IDH1 2-IN-1 reduces inflammation and promotes apoptosis, demonstrating significant anti-tumor activity. It is also utilized in leukemia research.

IDH1 Inhibitor 9 (compound 11S) (2, 4, 8, 10 µM) induces apoptosis and causes cell cycle arrest in the S phase in a dose-dependent manner.

WT IDH1 Inhibitor 2 is a wild-type isocitrate dehydrogenase 1 (WT IDH1) inhibitor (IC50: 120 nM) and is a mutant R132H IDH1 inhibitor, an isoform of GSK321 with wild-type cross-reactivity.

Mutant IDH1-IN-3 (Compound 1) is a selective allosteric inhibitor targeting the mutant isocitrate dehydrogenase 1 (IDH1), with an IC50 of 13 nM for R132HIDH1. It effectively suppresses the production of D-2-hydroxyglutarate (2HG) in cells and is applicable for research in oncology.

(R)-IDHP, an isomer of IDHP and a metabolite of salvia, exhibits vasorelaxant properties by inhibiting calcium (Ca 2+) release and inward flow through both voltage-dependent and receptor-operated calcium channels in vascular smooth muscle cells. It is utilized in cardiovascular disease research [1].

mIDH1-IN-1 (compound 43) is a potent and selective inhibitor of mIDH1 (isocitrate dehydrogenase 1 mutant) with an IC50 of 961.5 nM, and it effectively inhibits the production of 2-HG (2-hydroxyglutarate) in HT1080 cells. It also exhibits significant anti-proliferative effects on IDH1 mutant U-87 cells (IC50: 41.8 nM). mIDH1-IN-1 is an anti-tumor agent used to study IDH1 mutant solid tumors.

(S,R)-WT IDH1 Inhibitor 2 is a selective and potent mutant IDH1 inhibitor that inhibits R132G (IC50: 2.9 nM), R132C (IC50: 3.8 nM), R132H (IC50: 4.6 nM) and WT IDH1 (IC50: 46 nM) with 100-fold higher selectivity than IDH2. 100-fold higher selectivity than IDH2. (S,R)-WT IDH1 Inhibitor 2 is investigated in acute myeloid leukemia (AML) and other cancers for its ability to induce intracellular 2-HG reduction, failure of myeloid differentiation block, and induction of granulocyte differentiation at the level of leukemia mother cells and more immature stem cells.

IDH1 Inhibitor 5 (compound 2) is an IDH1 (isocitrate dehydrogenase 1) inhibitor with an IC50 of 64.4 nM for MOG cells and an IC50 of 34.9 nM for wild-type IDH1 glioma cells expressing exogenous mutant IDH1 R132H protein.