Isocitrate Dehydrogenase (IDH) Inhibitor

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 IDH1^R132H, IDH1^R132C and IDH1^wt, respectively. IDH889 shows potent cellular inhibition of R-2-hydroxyglutarate (2-HG) production with an IC₅₀ of 0.014 μM.

ZD-2767P (Compound 1) is a reversible and competitive inhibitor of IDH1, with its IC₅₀ value being 410 nM.

Mutant IDH1-IN-2 is a inhibitor of mutant Isocitrate dehydrogenase (IDH) proteins, with IC50 of in LS-MS biochemical assay, IC50 of 16.6 nM in Fluorescence biochemical assay.

Mutant IDH1-IN-6 is a potent, selective and orally active mutant isocitrate dehydrogenase (IDH) inhibitor with IC₅₀s 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. Mutant IDH1-IN-6 is less active at inhibiting the IDH wild-type enzymes.

IDH1 Inhibitor 1 is a potent, orally bioavailable, brain-penetrant and selective mutant IDH1 inhibitor with IC₅₀s of 0.021 μM, 0.045 μM, and 2.52 μM for IDH1^R132H, IDH1^R132C, and IDH1^WT, respectively. Anticancer activity.

IDH1 Inhibitor 7 (Compound 88) is an IDH1 inhibitor with an IC₅₀ of less than 100 nM.

IDH1 Inhibitor 7-d₂ is the deuterium labeled IDH1 Inhibitor 7 (HY-150238). IDH1 Inhibitor 7 is an IDH1 inhibitor with an IC₅₀ of less than 100 nM.

Mutant IDH1 inhibitor is a potent mutant IDH1 R132H inhibitor with IC₅₀ of < 72 nM.

IDH1 Inhibitor 3 (compound 6f) is a mutant isocitric dehydrogenase 1 (IDH1) inhibitor, with an IC₅₀ of 45 nM for IDH1^R132H.

TC-E 5008 is a potent mutant IDH1 inhibitor with K_i values of 190 nM and 120 nM for R132H and R132C IDH1 mutants, respectively. TC-E 5008 exhibits very weak activity against WT-IDH1 with a K_i value of 12.3 μM. TC-E 5008 has anti-proliferative activity on multiple ER positive breast cancer cell lines.

(S,S)-GSK321 is a (S,S)-enantiomer of GSK321.

Mutant IDH1-IN-4 (compound 434) is an inhibitor of mutant Isocitrate dehydrogenase 1 (IDH 1), with IC₅₀ values of ≤ 0.5 μM for mutant IDH1 in R132H, HT1080 and U87R132H cells.

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.

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.

IDH2^R140Q-IN-2 (compound 36) is an an orally active IDH2^R140Q inhibitor (IC₅₀: 29 nM). IDH2^R140Q-IN-2 reduces D2HG production in TF-1 cell lines expressing mutant IDH2^R140Q (IC₅₀: 10 nM). IDH2^R140Q-IN-2 suppresses D2HG levels in tumor tissue. IDH2^R140Q-IN-2 can be used for research of acute myeloid leukemia (AML).

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.

IDH2R140Q-IN-1 (compound C6) is a potent inhibitor of IDH2^R140Q, with an IC₅₀ of 6.1 nM. IDH2R140Q-IN-1 can be used for the research of acute myeloid leukemia.

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.

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 IDH2^R140Q and IDH2^R172K, respectively.

IDH-C227 is a potent and selective IDH1^R132H inhibitor. IDH-C227 has anticancer effcts.