-Octyl-α-hydroxyglutarate Chemical Structure.png)
Physicochemical Properties
| Molecular Formula | C13H24O5 |
| Molecular Weight | 260.3267 |
| Exact Mass | 260.162 |
| CAS # | 1391194-67-4 |
| PubChem CID | 71749054 |
| Appearance | White to off-white solid powder |
| Density | 1.1±0.1 g/cm3 |
| Boiling Point | 420.5±35.0 °C at 760 mmHg |
| Flash Point | 152.3±19.4 °C |
| Vapour Pressure | 0.0±2.2 mmHg at 25°C |
| Index of Refraction | 1.473 |
| LogP | 3.03 |
| Hydrogen Bond Donor Count | 2 |
| Hydrogen Bond Acceptor Count | 5 |
| Rotatable Bond Count | 12 |
| Heavy Atom Count | 18 |
| Complexity | 240 |
| Defined Atom Stereocenter Count | 1 |
| SMILES | CCCCCCCCOC(=O)[C@@H](CCC(=O)O)O |
| InChi Key | UJZOKTKSGUOCCM-LLVKDONJSA-N |
| InChi Code | InChI=1S/C13H24O5/c1-2-3-4-5-6-7-10-18-13(17)11(14)8-9-12(15)16/h11,14H,2-10H2,1H3,(H,15,16)/t11-/m1/s1 |
| Chemical Name | (4R)-4-hydroxy-5-octoxy-5-oxopentanoic 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 Note: Please store this product in a sealed and protected environment, avoid exposure to moisture. |
| 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
| ln Vitro |
When (2R)-octyl-α-hydroxyglutarate, a modified form of 2-hydroxyglutarate with high cellular uptake, was added to IDH1-WT HeLa cells, it caused a dose-dependent DSB in log-phase cells and increased sex. It has been applied to investigate D-2-hydroxyglutarate's role in mitochondrial oxidative processes in cancer cells with IDH1 mutations [1]. Treatment of IDH1-WT HeLa cells with (2R)-Octyl-α-hydroxyglutarate resulted in a dose-dependent increase in DNA double-strand breaks (DSBs) in log-phase cells, as measured by neutral comet assay. A concentration of 900 µM induced the highest amount of DSBs, similar to the level caused by 5 Gy of ionizing radiation. This effect was rapid, occurring within 2 hours of exposure. [1] Exposure of IDH1-WT U2OS DR-GFP reporter cells to (2R)-Octyl-α-hydroxyglutarate caused a dose-dependent suppression of homologous recombination (HR) activity. Similar HR suppression was observed with the (S) enantiomer (octyl ester), but not with the octyl-α-ketoglutarate control. [1] Pre-treatment of IDH1-WT HCT116 cells with 900 µM (2R)-Octyl-α-hydroxyglutarate for 4 days conferred increased sensitivity to the PARP inhibitor BMN-673 in short-term growth delay assays. [1] Treatment with (2R)-Octyl-α-hydroxyglutarate (900 µM and 300 µM) was able to phenocopy the HR defect (measured by plasmid-based HR reporter assay) seen in IDH1-mutant cells or in BRCA2-deficient cells, when applied to various wild-type cell lines (HeLa, HCT116, DLD1, PEO1 C4-2). [1] Treatment of IDH1-WT primary patient-derived glioma cell lines with 300 µM (2R)-Octyl-α-hydroxyglutarate for 7 days recapitulated the phenotype of IDH1-mutant lines: it increased baseline DSBs (comet assay), increased γH2AX/53BP1 foci, and conferred sensitivity to the PARP inhibitor BMN-673 in clonogenic survival assays. [1] |
| Cell Assay |
Neutral Comet Assay: To assess DNA double-strand breaks (DSBs), cells were trypsinized, washed with PBS, and suspended in LM Agarose. Neutral electrophoresis was conducted at 21 V for 1 hour. Data were collected with a fluorescence microscope and analyzed using Open Comet software. Data are presented as the mean tail moment +/- SEM from at least 3 biological replicates with more than 100 cells analyzed per replicate. For experiments with (2R)-Octyl-α-hydroxyglutarate, cells were typically treated with the indicated concentrations for 24 hours before assay, unless otherwise specified. [1] U2OS DR-GFP Reporter Assay: To test the effect on homologous recombination (HR), U2OS DR-GFP cells were treated with (2R)-Octyl-α-hydroxyglutarate for the indicated times (e.g., 24 hours). Then, 10^6 cells were transfected in triplicate with 4 µg of the I-SceI expression plasmid (pI-Scel) using nucleofection. Seventy-two hours after transfection, cells were analyzed for GFP expression by flow cytometry. The percentage of GFP-positive cells was calculated and normalized to controls to determine relative HR efficiency. [1] Short-term Growth Delay Assay: For synergy or sensitivity tests, cells were plated in 96-well plates. After 24 hours, media were changed, and drugs (e.g., BMN-673) were added at varying concentrations. For experiments involving pre-treatment with (2R)-Octyl-α-hydroxyglutarate, cells were cultured with the indicated concentration (e.g., 900 µM) for several days (e.g., 4-10 days) before plating and drug addition. At 96 hours after drug addition, cells were fixed, stained with Hoechst, imaged, and counted. [1] |
| References |
[1]. 2-Hydroxyglutarate produced by neomorphic IDH mutations suppresses homologousrecombination and induces PARP inhibitor sensitivity. Sci Transl Med. 2017 Feb 1;9(375). |
| Additional Infomation |
(2R)-Octyl-α-hydroxyglutarate is a cell-permeable octyl ester derivative of (R)-2-hydroxyglutarate (R-2HG). It was used in this study as a pharmacological tool to deliver 2HG into cells, demonstrating that 2HG itself is sufficient to induce a homologous recombination (HR) defect and confer PARP inhibitor sensitivity, thereby mimicking the "BRCAness" phenotype caused by mutant IDH1/2. [1] The study found that both (R)- and (S)- enantiomers of 2HG (in octyl ester forms) could induce this HR defect, suggesting the effect is mediated by 2HG's inhibition of α-ketoglutarate-dependent dioxygenases rather than being enantiomer-specific. [1] Typical working concentrations used in cell culture experiments ranged from 300 µM to 900 µM. [1] |
Solubility Data
| Solubility (In Vitro) | DMSO : ~100 mg/mL (~384.13 mM) |
| Solubility (In Vivo) |
Solubility in Formulation 1: ≥ 2.5 mg/mL (9.60 mM) (saturation unknown) in 10% DMSO + 40% PEG300 + 5% Tween80 + 45% Saline (add these co-solvents sequentially from left to right, and one by one), clear solution. For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 25.0 mg/mL clear DMSO stock solution to 400 μL PEG300 and mix evenly; then add 50 μL Tween-80 to the above solution and mix evenly; then add 450 μL normal saline to adjust the volume to 1 mL. Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH₂ O to obtain a clear solution. Solubility in Formulation 2: ≥ 2.5 mg/mL (9.60 mM) (saturation unknown) in 10% DMSO + 90% (20% SBE-β-CD in Saline) (add these co-solvents sequentially from left to right, and one by one), clear solution. For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 25.0 mg/mL clear DMSO stock solution to 900 μL of 20% SBE-β-CD physiological saline solution and mix evenly. 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. Solubility in Formulation 3: ≥ 2.5 mg/mL (9.60 mM) (saturation unknown) in 10% DMSO + 90% Corn Oil (add these co-solvents sequentially from left to right, and one by one), clear solution. For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 25.0 mg/mL clear DMSO stock solution to 900 μL of corn oil and mix evenly. (Please use freshly prepared in vivo formulations for optimal results.) |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 3.8413 mL | 19.2064 mL | 38.4128 mL | |
| 5 mM | 0.7683 mL | 3.8413 mL | 7.6826 mL | |
| 10 mM | 0.3841 mL | 1.9206 mL | 3.8413 mL |