Isocitrate Dehydrogenase (IDH) Inhibitor

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.

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.

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.

AGI-6780 that potently and selectively inhibits the tumor-associated mutant IDH2^R140Q with IC₅₀ of 23±1.7 nM. AGI-6780 is less potent against IDH2^WT with IC₅₀ of 190±8.1 nM.

AGI-5198 (IDH-C35) is a potent and selective mutant IDH1^R132H inhibitor with an IC₅₀ of 0.07 μM.

GSK864, a chemical probe, is an isocitrate dehydrogenase 1 (IDH1) mutant inhibitor; inhibits IDH1 mutants R132C, R132H, and R132G with IC₅₀ values of 8.8, 15.2 and 16.6 nM.

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

GSK321 is a potent, selective mutant IDH1 inhibitor with IC₅₀ values of 2.9, 3.8, 4.6 and 46 nM for R132G, R132C, R132H and WT IDH1, respectively, and >100-fold selectivity over IDH2. GSK321 induces decrease in intracellular α-Hydroxyglutaric acid (2-HG) (HY-113038B), abrogation of the myeloid differentiation block and induction of granulocytic differentiation at the level of leukemic blasts and more immature stem-like cells. GSK321can be used for research of acute myeloid leukemia (AML) and other cancers.

BAY-1436032 is a novel pan-mutant isocitrate dehydrogenase 1 (IDH1) inhibitor.

Enasidenib mesylate is a first-in-class, oral, potent, reversible, selective inhibitor of the IDH2 mutant enzymes.

DS-1001b is an orally active, blood-brain permeable, potent IDH-1 (isocitrate dehydrogenase-1) mutant inhibitor. DS-1001b has antitumor activity.

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 (IDH1^R132H), 28 nM (IDH1^R132C), 6.14 µM (IDH1^WT)).

IDH1 Inhibitor 2 (compound 13) is a potent wild-type IDH1 inhibitor that exerts its activity through covalent modification of His315 with an IC₅₀ value of 110 nM. IDH1 Inhibitor 2 can dose-dependently reduce the intracellular reduced glutamine metabolic flux, thereby affecting cellular metabolic homeostasis. IDH1 Inhibitor 2 can be used to study the role of IDH1 in cellular metabolic regulation and cancer development.

IDH1 Inhibitor 8 (91) is isocitrate dehydrogenase 1 (IDH1) inhibitor. IDH1 Inhibitor 8 can be used for the research of cancer.

DIM-C-pPhCO2Me is a nuclear receptor 4A1 (NR4A1) antagonist. DIM-C-pPhCO2Me induces Apoptosis. DIM-C-pPhCO2Me decreases PAX3-FOXO1A, N-Myc, Rassf4, MyoD1, Grem1, and DAPK1 proteins. DIM-C-pPhCO2Me decreases expression of TXNDC5 and IDH1, induces markers of ER stress (CHOP, ATF4 and p-PERK). DIM-C-pPhCO2Me inhibits renal cell carcinoma, breast cancer. DIM-C-pPhCO2Me can also be used in rhabdomyosarcoma research.

Safusidenib (AB-291; DS-1001) is an orally bioavailable, selective mutant IDH1 inhibitor. Safusidenib strongly inhibits mutant IDH1 but not wild-type IDH1. Safusidenib impairs tumor activity in chondrosarcoma. Safusidenib exhibits activity against IDH1R132H, and IDH1R132C with IC₅₀s of 15, and 130 nM in assays without any preincubation, respectively.

(R,R)-GSK321 is a wild-type isocitrate dehydrogenase 1 (WT IDH1) inhibitor with an IC₅₀ value of 120 nM. (R,R)-GSK321 as a mutant R132H IDH1 inhibitor, is an isomer of GSK321 with some wild-type cross reactivity.

Oxalomalic acid (Oxalomalate) trisodium is a aconitase and NADP-dependent isocitrate dehydrogenase inhibitor. Oxalomalic acid trisodium inhibits nitrite production and iNOS protein expression in lipopolysaccharide (HY-D1056)-activated J774 macrophages.

Mutant IDH1-IN-1 (Agios 135) is a selective mutant IDH1 inhibitor with activity against both IDH1^R132H and IDH1^R132C. Mutant IDH1-IN-1 reduces the level of 2-hydroxyglutarate (2-HG), stabilizes mutant IDH1 protein, and restores blocked monocyte differentiation. Mutant IDH1-IN-1 can be used in tumor-related research.

trans-3-(3-Pyridyl) acrylic acid is an unsaturated carboxylic acid and synthetic building block, which serves as a synthetic precursor of 3-(3-pyridyl) propanoic acid. trans-3-(3-Pyridyl) acrylic acid can be used to prepare dual mutant IDH1/NAMPT inhibitors and PGE₂ antagonist analogs. In addition, trans-3-(3-Pyridyl) acrylic acid exhibits antiviral activity against tobacco mosaic virus (TMV).