D-alpha-Hydroxyglutaric acid (disodium salt)

103404-90-6

C5H6Na2O5

H2O : >= 32 mg/mL (166.60 mM)

Metabolic Enzyme/Protease; NF-kappaB; Immunology/Inflammation

D-alpha-Hydroxyglutaric acid disodium salt is a weak competitive alpha-Ketoglutarate(alpha-KG)-dependent dioxygenase inhibitor with K_i of 10.87+/-1.85 mM. K_i for L-Hydroxyglutaric acid (L-2-HG) is 0.628+/-0.036 mM. IC50 & Target: Ki: 10.87+/-1.85 mM (alpha-KG)^[1] In Vitro: Addition of 50 mM and 100 mM of D-alpha-Hydroxyglutaric acid (D-2-HG) results in partial and nearly complete inhibition of CeKDM7A, respectively. To further examine the mode of interaction between alpha-KG and D-2-HG, CeKDM7A are incubated with a fixed concentration (50 mM) of D-2-HG and increasing amount of alpha-KG. A partial inhibition of KDM7A toward both H3K9me2 and H3K27me2 peptides is observed in the presence of 50 mM D-2-HG and 100 uM alpha-KG. Addition of 300 uM alpha-KG is capable of reversing the inhibition of CeKDM7A by 50 mM D-2-HG, indicating that D-2-HG is a weak competitive inhibitor against alpha-KG toward the CeKDM7A demethylase. D-2-HG with K_i of 10.87+/-1.85 mM for inhibiting KDM5B/JARID1B/PLU-1^[1]. D-alpha-Hydroxyglutaric acid (R-2HG) increases the lifespan of C. elegans. (R)-2HG interacts distinctly with the alpha-KG dependent dioxygenases. The intracellular (R)-2HG levels are 20-100 fold higher in U87 and HCT 116 cells expressing IDH1(R132H) than in control cells. The elevated (R)-2HG levels are comparable to those found in cells treated with octyl (R)-2HG, and levels reported for IDH1-mutant tumor samples^[2].