Disodium (R)-2-Hydroxyglutarate
Information here is from (R)-2-hydroxyglutarate ((R)-2HG) instead of Disodium (R)-2-Hydroxyglutarate. (R)-2HG inhibits adenosine triphosphate (ATP) synthase [1]. The IC50 value has not been found.
ATP synthase containing a rotary motor involved in energy conversion in organisms. It produces ATP from inorganic phosphate and adenosine diphosphate (ADP). It functions using the energy from a respiration- or photosynthesis-generated transmembrane proton-motive force [2].
Data showed that (R)-2HG accumulated in human cancers carrying mutant isocitrate dehydrogenase (IDH) 1 and 2 genes. In IDH1 mutant cells, the inhibition of (R)-2HG to ATP synthase was mirrored. This indicated that (R)-2HG has a growth-suppressive function. In glioblastoma cells, consistently, the inhibition of (R)-2HG to ATP synthase is sufficient for tumor cell killing and growth arrest under glucose limitation conditions, e.g., when ketone bodies are supplied for energy instead of glucose. In cells, treatment with (R)-2HG decreased the rate of ATP synthase-linked oxygen consumption [1].
The normal cellular concentration of (R)-2HG is 200 mM. At this concentration, ATP synthase is unlikely to be significantly inhibited by (R)-2HG. In glioma patients with IDH mutations, (R)-2HG accumulates to 10-100 times of normal levels, and ATP synthase would be possible to be inhibited. (R)-2HG extended the lifespan of C. elegans, in a similar way of α-KG. Data showed that 2-HG increased lifespan ATP-synthase-dependently [1].
References:
[1]. Fu X, Chin RM, Vergnes L, et al. 2-Hydroxyglutarate inhibits ATP synthase and mTOR signaling. Cell metabolism, 2015, 22(3): 508-515.
[2]. Stock D, Leslie AGW and Walker JE. Molecular architecture of the rotary motor in ATP synthase. Science, 1999, 286(5445): 1700-1705.
| Physical Appearance | A solid |
| Storage | Store at -20°C |
| M.Wt | 192.08 |
| Cas No. | 103404-90-6 |
| Formula | C5H6Na2O5 |
| Solubility | insoluble in EtOH; insoluble in DMSO; ≥9.1 mg/mL in H2O |
| Chemical Name | sodium (R)-2-hydroxypentanedioate |
| SDF | Download SDF |
| Canonical SMILES | O[C@](C([O-])=O)([H])CCC([O-])=O.[Na+].[Na+] |
| Shipping Condition | Small Molecules with Blue Ice, Modified Nucleotides with Dry Ice. |
| General tips | We do not recommend long-term storage for the solution, please use it up soon. |
| Cell experiment:[1] | |
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Cell lines |
TF-1 cells |
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Reaction Conditions |
100 ~ 500 μM (R)-2HG for 0 ~ 12 d incubation |
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Applications |
TF-1 cells passaged in the presence of the cell membrane-permeable version of (R)-2HG became growth factor-independent and no longer differentiated in response to erythropoietin (EPO). Promotion of growth factor-independence and loss of EPO-responsiveness by (R)-2HG was dose-dependent and passage-dependent. (R)-2HG was sufficient to promote leukemogenesis and its effects were reversible. |
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Note |
The technical data provided above is for reference only. |
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References: 1. Losman JA, Looper RE, Koivunen P, et al. (R)-2-hydroxyglutarate is sufficient to promote leukemogenesis and its effects are reversible. Science, 2013, 339(6127): 1621-1625. |
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Quality Control & MSDS
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Chemical structure
