Alpha-Hydroxyglutaric acid (2-Hydroxyglutarate) is the alpha-hydroxy acid form of glutaric acid. α-Hydroxyglutaric acid is a competitive inhibitor of multiple α-ketoglutarate-dependent dioxygenases such as the TET family of histone demethylases and 5-methlycytosine (5mC) hydroxylases. agent.

Physicochemical Properties

Molecular Formula	C5H8O5
Molecular Weight	148.11
Exact Mass	146.022
CAS #	2889-31-8
Related CAS #	40951-21-1 (di-hydrochloride salt)
PubChem CID	43
Appearance	Colorless to light yellow liquid
LogP	-1
Hydrogen Bond Donor Count	3
Hydrogen Bond Acceptor Count	5
Rotatable Bond Count	4
Heavy Atom Count	10
Complexity	141
Defined Atom Stereocenter Count	0
SMILES	OC(CCC(C(=O)O)O)=O
InChi Key	HWXBTNAVRSUOJR-UHFFFAOYSA-N
InChi Code	InChI=1S/C5H8O5/c6-3(5(9)10)1-2-4(7)8/h3,6H,1-2H2,(H,7,8)(H,9,10)
Chemical Name	2-hydroxypentanedioic acid
HS Tariff Code	2934.99.9001
Storage	Powder-20°C 3 years 4°C 2 years In solvent -80°C 6 months -20°C 1 month
Shipping Condition	Room temperature (This product is stable at ambient temperature for a few days during ordinary shipping and time spent in Customs)

Biological Activity

Targets	Microbial Metabolite Human Endogenous Metabolite
ln Vitro	Acute myeloid leukemia and gliomas are common causes of Isocitrate Dehydrogenase 1 (IDH1) and IDH2 mutations, which result in concurrent loss and gain of activities in the synthesis of α-ketoglutarate (α-KG) and α-Hydroxyglutaric acid (2-Hydroxyglutarate), respectively [1]. Numerous histone demethylases are inhibited by α-Hydroxyglutaric acid (2-Hydroxyglutarate). The position of α-KG and α-Hydroxyglutaric acid in the active site of histone demethylases is identical. ) prevents TET 5-methylcytosine hydroxylases from acting[1]. α-Hydroxyglutaric acid (2-Hydroxyglutarate; 10–50 mM) treatment of U-87MG cells causes an increase in HIF-1α and a decrease in endostatin[1].
References	[1]. Oncometabolite 2-hydroxyglutarate is a competitive inhibitor of α-ketoglutarate-dependent dioxygenases. Cancer Cell. 2011 Jan 18;19(1):17-30.
Additional Infomation	2-hydroxyglutaric acid is a 2-hydroxydicarboxylic acid that is glutaric acid in which one hydrogen alpha- to a carboxylic acid group is substituted by a hydroxy group. It has a role as a metabolite and a mouse metabolite. It is a 2-hydroxydicarboxylic acid and a dicarboxylic fatty acid. It is functionally related to a glutaric acid. It is a conjugate acid of a 2-hydroxyglutarate(1-) and a 2-hydroxyglutarate. 2-Hydroxyglutaric acid has been reported in Drosophila melanogaster, Arabidopsis thaliana, and Saccharomyces cerevisiae with data available. Alpha-Hydroxyglutarate is the base form of alpha-hydroxyglutaric acid, which is an intermediate in the synthesis of alpha-ketoglutaric acid. Alpha-hydroxyglutarate accumulates in the blood of patients with 2-hydroxyglutaric aciduria; an organic acid metabolism disorder, which is caused by the genetic mutation of one of the enzymes responsible for the conversion of 2-hydroxyglutaric acid to alpha-ketoglutaric acid. 2-hydroxyglutaric acid is a metabolite found in or produced by Saccharomyces cerevisiae.

Solubility Data

Solubility (In Vitro)

May dissolve in DMSO (in most cases), if not, try other solvents such as H2O, Ethanol, or DMF with a minute amount of products to avoid loss of samples

Solubility (In Vivo)

Note: Listed below are some common formulations that may be used to formulate products with low water solubility (e.g. < 1 mg/mL), you may test these formulations using a minute amount of products to avoid loss of samples. Injection Formulations (e.g. IP/IV/IM/SC) Injection Formulation 1: DMSO : Tween 80： Saline = 10 : 5 : 85 (i.e. 100 μL DMSO stock solution → 50 μL Tween 80 → 850 μL Saline) *Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH ₂ O to obtain a clear solution. Injection Formulation 2: DMSO : PEG300 ：Tween 80 : Saline = 10 : 40 : 5 : 45 (i.e. 100 μL DMSO → 400 μLPEG300 → 50 μL Tween 80 → 450 μL Saline) Injection Formulation 3: DMSO : Corn oil = 10 : 90 (i.e. 100 μL DMSO → 900 μL Corn oil) Example: Take the Injection Formulation 3 (DMSO : Corn oil = 10 : 90) as an example, if 1 mL of 2.5 mg/mL working solution is to be prepared, you can take 100 μL 25 mg/mL DMSO stock solution and add to 900 μL corn oil, mix well to obtain a clear or suspension solution (2.5 mg/mL, ready for use in animals). Injection Formulation 4: DMSO : 20% SBE-β-CD in saline = 10 : 90 [i.e. 100 μL DMSO → 900 μL (20% SBE-β-CD in saline)] *Preparation of 20% SBE-β-CD in Saline (4°C，1 week): Dissolve 2 g SBE-β-CD in 10 mL saline to obtain a clear solution. Injection Formulation 5: 2-Hydroxypropyl-β-cyclodextrin : Saline = 50 : 50 (i.e. 500 μL 2-Hydroxypropyl-β-cyclodextrin → 500 μL Saline) Injection Formulation 6: DMSO : PEG300 : castor oil : Saline = 5 : 10 : 20 : 65 (i.e. 50 μL DMSO → 100 μLPEG300 → 200 μL castor oil → 650 μL Saline) Injection Formulation 7: Ethanol : Cremophor : Saline = 10： 10 : 80 (i.e. 100 μL Ethanol → 100 μL Cremophor → 800 μL Saline) Injection Formulation 8: Dissolve in Cremophor/Ethanol (50 : 50), then diluted by Saline Injection Formulation 9: EtOH : Corn oil = 10 : 90 (i.e. 100 μL EtOH → 900 μL Corn oil) Injection Formulation 10: EtOH : PEG300：Tween 80 : Saline = 10 : 40 : 5 : 45 (i.e. 100 μL EtOH → 400 μLPEG300 → 50 μL Tween 80 → 450 μL Saline) Oral Formulations Oral Formulation 1: Suspend in 0.5% CMC Na (carboxymethylcellulose sodium) Oral Formulation 2: Suspend in 0.5% Carboxymethyl cellulose Example: Take the Oral Formulation 1 (Suspend in 0.5% CMC Na) as an example, if 100 mL of 2.5 mg/mL working solution is to be prepared, you can first prepare 0.5% CMC Na solution by measuring 0.5 g CMC Na and dissolve it in 100 mL ddH2O to obtain a clear solution; then add 250 mg of the product to 100 mL 0.5% CMC Na solution, to make the suspension solution (2.5 mg/mL, ready for use in animals). Oral Formulation 3: Dissolved in PEG400 Oral Formulation 4: Suspend in 0.2% Carboxymethyl cellulose Oral Formulation 5: Dissolve in 0.25% Tween 80 and 0.5% Carboxymethyl cellulose Oral Formulation 6: Mixing with food powders Note: Please be aware that the above formulations are for reference only. InvivoChem strongly recommends customers to read literature methods/protocols carefully before determining which formulation you should use for in vivo studies, as different compounds have different solubility properties and have to be formulated differently.  (Please use freshly prepared in vivo formulations for optimal results.)

Preparing Stock Solutions		1 mg	5 mg	10 mg
	1 mM	6.7517 mL	33.7587 mL	67.5174 mL
	5 mM	1.3503 mL	6.7517 mL	13.5035 mL
	10 mM	0.6752 mL	3.3759 mL	6.7517 mL

*Note: Please select an appropriate solvent for the preparation of stock solution based on your experiment needs. For most products, DMSO can be used for preparing stock solutions (e.g. 5 mM, 10 mM, or 20 mM concentration); some products with high aqueous solubility may be dissolved in water directly. Solubility information is available at the above Solubility Data section. Once the stock solution is prepared, aliquot it to routine usage volumes and store at -20°C or -80°C. Avoid repeated freeze and thaw cycles.