Isocitrate Dehydrogenase (IDH) 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].

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.

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.

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 K_i 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.

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.

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.

IDH-305 (Standard) is the analytical standard of IDH-305 (HY-104036). This product is intended for research and analytical applications. IDH-305 is an orally available, mutant-selective and brain-penetrant IDH1 inhibitor that targets IDH1 (R132) mutation. IDH-305 exhibits greater than 200 fold selectivity for mutant IDH1 isoforms vs. WT (IC₅₀= 27 nM (IDH1R132H), 28 nM (IDH1R132C), 6.14 µM (IDH1WT)).

Mutant IDH1-IN-7 is a highly selective Isocitrate Dehydrogenase 1 (IDH1) R132H (IC₅₀ = 0.26 μM, K_d = 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.

BRD2879 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.

AGI-14100 is a metabolically stable and orally available mIDH1 inhibitor (IC₅₀=6 nM). The pharmacochemical optimization of AGI-14100 is aimed at eliminating hPXR activation, resulting in the final drug candidate AG-120. AG-120 can be used in the study of cancers carrying IDH1 mutations. The discovery and development of AGI-14100 can be used for further studies of mutant isocitrate dehydrogenase 1 (mIDH1) inhibitors.

Ivosidenib (Standard) is the analytical standard of Ivosidenib (HY-18767). This product is intended for research and analytical applications. Ivosidenib (AG-120) is an orally active inhibitor of isocitrate dehydrogenase 1 mutant (mIDH1) enzyme, it exhibits profound d-2-hydroxyglutatrate (2-HG) lowering in vivo. Ivosidenib (AG-120) has the potential for AML therapy due to its acceptable safety profile and clinical activity.

DA-11004 is an orally active NADP-dependent isocitrate dehydrogenase (IDPc) inhibitor with an IC₅₀ of 1.49 μM. DA-11004 reduces NADPH production, decreases plasma NADPH levels and plasma free fatty acid levels. DA-11004 lowers plasma glucose levels, inhibits fatty acid synthesis in adipose tissue, reduces weight gain and decreases epididymal and retroperitoneal fat content. DA-11004 exerts antidiabetic effects in mice fed a high-fat and high-sugar diet. DA-11004 can be used for research on obesity and type 2 diabetes.

IDH1 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.

mIDH1-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.

Vorasidenib (Standard) is the analytical standard of Vorasidenib (HY-104042). This product is intended for research and analytical applications. Vorasidenib (AG-881) is an orally available, brain penetrant second-generation dual mutant isocitrate dehydrogenases 1 and 2 (mIDH1/2) inhibitor. Vorasidenib (AG-881) exhibits nanomolar inhibition of (D)-2-hydroxyglutarate (D-2-HG), and the IC₅₀ ranges of 0.04~22 nM against IDH1 R132C, IDH1 R132G, IDH1 R132H and IDH1 R132S and 7~14 nM against IDH2 R140Q and 130 nM against IDH2 R172K. Vorasidenib can be used for the study of grade 2 astrocytoma or oligodendroglioma with a susceptible IDH1/2 mutation.

Mutant 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.

Alternaphenol B2 is a selective IDH1 inhibitor from the coral-derived fungus Parengyodontium album SCSIO SX7W11. Alternaphenol B2 shows inhibitory activity against isocitrate dehydrogenase mutant R132H (IDH1m), with IC₅₀ values of 41.9 μM.

Enasidenib (Standard) is the analytical standard of Enasidenib. This product is intended for research and analytical applications. 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 (mesylate) (Standard) is the analytical standard of Enasidenib (mesylate). This product is intended for research and analytical applications. Enasidenib mesylate is a first-in-class, oral, potent, reversible, selective inhibitor of the IDH2 mutant enzymes.

BAY-1436032 (Standard) is the analytical standard of BAY-1436032 (HY-100020). This product is intended for research and analytical applications. BAY-1436032 is a novel pan-mutant isocitrate dehydrogenase 1 (IDH1) inhibitor.