2-hg

TFMB-(R)-2-HG is a cell membrane-permeable (R)-2-HG, an oncogenic factor in acute myeloid leukemia. It impairs SCF ER-Hoxb8 cell differentiation in response to estrogen withdrawal.

TFMB-(S)-2-HG (TFMB S 2 HG) is a highly effective inhibitor of TET2, the 5'-methylcytosine hydroxylase. Additionally, it significantly inhibits the EglN prolyl hydroxylases. With its unique properties, TFMB-(S)-2-HG holds great promise for advancing research in the field of acute myeloid leukemia (AML).

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).

GSK864 is an IDH1 mutant inhibitor that inhibits IDH1 mutants R132C, R132H, and R132G, and is used in the study of cardiovascular and oncology diseases.

(2R)-Octyl-α-hydroxyglutarate ((2R)-Octyl-2-HG) is a modified form of D-isomer 2-hydroxyglutarate.

(2S)-Octyl-α-hydroxyglutarate ((2S)-Octyl-2-HG) is a modified form of the S-isomer of 2-Hydroxyglutarate.

Octyl-α-hydroxyglutarate (octyl-2-HG) enhances histone methylation and boosts the viability of LMP1-negative nasopharyngeal carcinoma (NPC) cells.

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.

AGI-026 (AGI-12026) is a novel and potent dual inhibitor of the mutant isocitrate dehydrogenase mIDH1/2 with the advantages of oral administration and penetration of the blood-brain barrier, with a drug concentration to plasma concentration ratio (brain/plasma ratio) of 1.5 in brain tissue, and the ability to reduce the accumulation of the carcinogenic metabolite d-2-hydroxyglutarate (2-HG), which is used in the study of mIDH gliomas.

L-2-Hydroxyglutaric acid (L-2-HG) is a compartmentalized metabolite and a substrate for L-2-hydroxyglutarate dehydrogenase (L2HGDH). It inhibits histone demethylases and increases the expression of ATF4 and its target genes by activating the mTOR pathway. L-2-Hydroxyglutaric acid mediates the mTOR-ATF4 signaling pathway and can be used in biosensor research.

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).

SNIPER(ABL)-047, a compound that links HG-7-85-01 (an ABL inhibitor) to MV-1 (an IAP ligand) via a linker, effectively decreases the BCR-ABL protein levels, achieving a DC50 value of 2 μM[1].

Mutant IDH1-IN-7 is a highly selective inhibitor of Isocitrate Dehydrogenase 1 (IDH1) with R132H mutation (IC50 = 0.26 μM, Kd = 2.1 μM) and R132C mutation (IC50 = 1.1 μM). It does not inhibit wild-type IDH1, IDH2-wt, or IDH2R140Q. Moreover, Mutant IDH1-IN-7 reduces the production of 2-hydroxyglutarate (2-HG) in U87-MG R132H cells (EC50 = 0.55 μM) and exhibits moderate antiproliferative effects on U87-MG R132H and HT-1080 cells.

GAT229 is a positive allosteric modulator of cannabinoid receptor 1 (CB1) and the S-(-) enantiomer of the CB1 modulator GAT211. It does not activate the receptor on its own but enhances the binding and activity of CB agonists. GAT229 (1 μM) enhances the binding of the CB1 full agonist CP 55,940 to CHO cells expressing human recombinant CB1 (hCB1), as well as the activity of 2-arachidonoyl glycerol , arachidonoyl ethanolamide , and CP 55,940 in arrestin2 recruitment assays and increases ERK1/2 and PLCβ3 phosphorylation in HEK293 cells expressing hCB1. GAT229 (1 μM) enhances depolarization-induced suppression of excitation but does not inhibit excitatory postsynaptic currents (EPSCs) in murine autaptic hippocampal neurons. GAT229 (0.2%, topical) reduces intraocular pressure by 5.8 and 7.7 mm Hg after 6 and 12 hours, respectively, in a transgenic mouse model of ocular hypertension using nose, ear, eye mutation (nee) mice.

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.

HG106, which is anti-inflammatory and may be used to treat the growth of diseases such as malignant tumours caused by mutations in the RAS gene., which is anti-inflammatory and may be used to treat the growth of diseases such as malignant tumours caused by mutations in the RAS gene.

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.

L6H9 is a novel inhibitor of myeloid differentiation factor 2 (MD2), suppressing HG-induced expression of ACE and AT1 receptor and Angiotensin II (AngII) production in renal NRK‐52E cells, resulting in the decrease in fibrosis markers such as TGF-β and collagen IV.

HG-10-102-01 is an inhibitor of leucine-rich repeat kinase 2 (LRRK2, IC50 of 20.3 nM).

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].

OAT1/3-IN-2 (compound 8) is a dual inhibitor of OAT1 and OAT3, demonstrating potential protective effects against Cys-Hg toxicity in HEK-OAT1 cells (10 μM) and may safeguard renal function. This compound is useful for investigating mercury-induced nephrotoxicity [1].

(Sodium) (2R)-Octyl-α-hydroxyglutarate is the sodium salt variant of (2R)-Octyl-α-hydroxyglutarate, which has been shown to possess anti-inflammatory properties [1].

TQ05310 is an orally active inhibitor of mutant IDH2, targeting both IDH2-R140Q (IC50=136.9 nM) and IDH2-R172K (IC50=37.9 nM) mutations. This compound suppresses the production of 2-hydroxyglutarate (2-HG) by inhibiting the enzymatic activity of mutant IDH2, and induces differentiation in cells expressing IDH2-R140Q and IDH2-R172K. TQ05310 is utilized in research on acute myeloid leukemia.