idh1 inhibitor 2

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

(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.

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.

Ivosidenib (AG-120) is an orally available inhibitor of isocitrate dehydrogenase type 1 (IDH1) with potential antineoplastic activity. It specifically inhibits a mutated form of IDH1 in the cytoplasm, preventing the formation of the oncometabolite 2-hydroxyglutarate (2 hG), which may induce cellular differentiation and inhibit cellular proliferation in IDH1-expressing tumor cells.

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.

D-α-Hydroxyglutaric acid disodium [Disodium (R)-2-Hydroxyglutarate] is a competitive inhibitor of α-ketoglutarate-dependent dioxygenases with a Ki of 0.628 mM.

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).

Olutasidenib (FT-2102) is under the study in the treatment of acute myeloid leukemia (AML) or myelodysplastic syndrome (MDS). Olutasidenib is a highly effective, brain penetrant, and selective inhibitor of the mutant Isocitrate dehydrogenase 1 (IDH1) (IC50: 21.2 nM and 114 nM for IDH1- R132H and IDH1- R132C, respectively).

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.

ML-309 is an inhibitor of mutant isocitrate dehydrogenase 1 (IDH1). It reversibly and selective inhibits IDH1R132H over wild-type IDH1 (IC50s = 96 and 36,500 nM, respectively). ML-309 reduces 2-hydroxyglutarate production in U87 MG glioblastoma cells (EC50 = 55 nM).

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.

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.

ML309 is a potent inhibitor of R132H mutant IDH1 capable of reducing 2-hydroxyglutarate production in U87 MG glioblastoma cells. ML309 is capable of potent and selective inhibition of mutant IDH1 and effectively lowers cell-based production of 2-HG in a U87MG mutant glioblastoma cell line.

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].

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.

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.