L-a-Hydroxyglutaric acid disodium salt (Synonyms: L-2-HG, L-2-Hydroxyglutarate, L-2-Hydroxyglutaric Acid, (S)-2-Hydroxypentanedioic Acid)

IC50: N/A

L-α-Hydroxyglutaric acid disodium salt is a salt form of L-α-Hydroxyglutaric acid. L-α-Hydroxyglutaric acid accumulates as a result of a rare defect in L-2-HG dehydogenase, resulting in the metabolic disorder L-α-hydroxyglutaric aciduria.

In vitro: It has been reported that L-α-Hydroxyglutaric acid disodium salt could be used as the collection buffer for increasing the recovery of hypoxia-inducible factor-1 α, which was a marker of hypoxia in human tumors [1]. In another previous study, L-α-Hydroxyglutaric acid disodium salt was also used in the radiolabeled conversion assay to evaluate its effect on the TET family of methyl hydroxylases [2].

In vivo: In the 30-day-old rats, L-α-Hydroxyglutaric acid was found to be able to significantly increase chemiluminescence, PCF and TBA-RS measurements and decrease the TAR values in cerebellum markedly. In addition, the L-α-Hydroxyglutaric acid-induced increase of TBA-RS was significantly attenuated by melatonin and also by the combinations of ascorbic acid and soluble alpha-tocopherol (Trolox) and of superoxide dismutase plus catalase but not by the inhibitor of nitric oxide synthase Nomega-nitro-L-arginine methyl ester (L-NAME), , superoxide dismutase or creatine or catalase alone in either cerebral structure [3].

Clinical trial: Up to now, L-a-Hydroxyglutaric acid disodium salt is still in the preclinical development stage.

References:
[1] Park SR,Kinders RJ,Khin S,et al.  Validation of a hypoxia-inducible factor-1 alpha specimen collection procedure and quantitative enzyme-linked immunosorbent assay in solid tumor tissues. Anal Biochem.2014 Aug 15;459:1-11.
[2] Evans B,Griner E.  Registered report: Oncometabolite 2-hydroxyglutarate is a competitive inhibitor of α-ketoglutarate-dependent dioxygenases. Elife.2015 Jul 31;4:e07420.
[3] Latini A,Scussiato K,Rosa RB,Leipnitz G,Llesuy S,Belló-Klein A,Dutra-Filho CS,Wajner M.  Induction of oxidative stress by L-2-hydroxyglutaric acid in rat brain. J Neurosci Res.2003 Oct 1;74(1):103-10.