(2R)-Octyl-α-hydroxyglutarate ((2R)-Octyl-2-HG)
(Synonyms: (2R)-辛基-Α-羟基戊二酸酯,(2R)-Octyl-2-HG) 目录号 : GC32754
(2R)-Octyl-α-hydroxyglutarate ((2R)-Octyl-2-HG)是2-Hydroxyglutarate的D型异构体的修饰物，具有细胞渗透性。
Cas No.:1391194-67-4
Sample solution is provided at 25 µL, 10mM.
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(2R)-Octyl-α-hydroxyglutarate ((2R)-Octyl-2-HG) is a cell-permeable modification of the D-isomer of 2-Hydroxyglutarate[1]. (2R)-Octyl-α-hydroxyglutarate is a membrane-permeable precursor of the oncometabolite (R)-2-hydroxyglutarate (R-2HG) produced in IDH1 mutant tumor cells[2]. (2R)-Octyl-α-hydroxyglutarate can act as a competitive inhibitor of α-ketoglutarate (α-KG)-dependent deoxygenase[3]. (2R)-Octyl-α-hydroxyglutarate can inhibit homology-directed repair (HDR) activity in IDH1/2 mutant cells[4].
In vitro, treatment of wild-type HCT116 cells with (2R)-Octyl-α-hydroxyglutarate (0-1000μM) for 10 days increased the sensitivity of the cells to poly(adenosine 5′-diphosphate ribose) polymerase (PARP) inhibitors[5]. Treatment of THP1 cells with (2R)-Octyl-α-hydroxyglutarate (300μM) for 7 days did not increase the level of (R)-2-hydroxyglutarate in the cells[6].
References:
[1] Reitman Z J, Duncan C G, Poteet E, et al. Cancer-associated isocitrate dehydrogenase 1 (IDH1) R132H mutation and d-2-hydroxyglutarate stimulate glutamine metabolism under hypoxia[J]. Journal of Biological Chemistry, 2014, 289(34): 23318-23328.
[2] Kim G H, Choi S Y, Oh T I, et al. IDH1R132H causes resistance to HDAC inhibitors by increasing NANOG in glioblastoma cells[J]. International Journal of Molecular Sciences, 2019, 20(11): 2679.
[3] Wang X, Liu R, Qu X, et al. α-Ketoglutarate-activated NF-κB signaling promotes compensatory glucose uptake and brain tumor development[J]. Molecular cell, 2019, 76(1): 148-162. e7.
[4] Dow J, Krysztofiak A, Liu Y, et al. Vulnerability of IDH1-mutant cancers to histone deacetylase inhibition via orthogonal suppression of DNA repair[J]. Molecular Cancer Research, 2021, 19(12): 2057-2067.
[5] Sulkowski P L, Corso C D, Robinson N D, et al. 2-Hydroxyglutarate produced by neomorphic IDH mutations suppresses homologous recombination and induces PARP inhibitor sensitivity[J]. Science translational medicine, 2017, 9(375): eaal2463.
[6] Bassal M A, Samaraweera S E, Lim K, et al. Germline mutations in mitochondrial complex I reveal genetic and targetable vulnerability in IDH1-mutant acute myeloid leukaemia[J]. Nature communications, 2022, 13(1): 2614.
(2R)-Octyl-α-hydroxyglutarate ((2R)-Octyl-2-HG)是2-Hydroxyglutarate的D型异构体的修饰物，具有细胞渗透性[1]。(2R)-Octyl-α-hydroxyglutarate是IDH1突变肿瘤细胞中产生的癌代谢物(R)-2-羟基戊二酸（R-2HG）的膜渗透性前体形式[2]。(2R)-Octyl-α-hydroxyglutarate能够用作α-酮戊二酸（α-KG）依赖性脱氧酶的竞争性抑制剂[3]。(2R)-Octyl-α-hydroxyglutarate能够抑制IDH1/2突变细胞中同源定向修复（HDR）活性[4]。
在体外，(2R)-Octyl-α-hydroxyglutarate（0-1000μM）处理野生型HCT116细胞10天，增加了细胞对聚（腺苷 5′-二磷酸核糖）聚合酶（PARP）抑制剂的敏感性[5]。(2R)-Octyl-α-hydroxyglutarate（300μM）处理THP1细胞7天，不会引起细胞中(R)-2-hydroxyglutarate水平升高[6]。
| Cell experiment [1]: | |
Cell lines | Wild-type HCT116 cells |
Preparation Method | After 4 days of culture in the presence of 300nM BMN-673 or DMSO control, wild-type HCT116 cells were treated with increasing concentrations of (2R)-Octyl-α-hydroxyglutarate ((2R)-Octyl-2-HG) (0-1000μM) for a short-term growth delay assay. For growth delay assays containing (2R)-octyl-2HG, cells were cultured with the indicated con centration for 10 days before plating. |
Reaction Conditions | 0-1000μM; 10 days |
Applications | Treatment of wild-type HCT116 cells with (2R)-Octyl-α-hydroxyglutarate conferred increased poly(adenosine 5′-diphosphate–ribose)polymerase (PARP) inhibitor sensitivity. |
| Cell experiment [2]: | |
Cell lines | THP1 cells |
Preparation Method | Parental THP1 cells seeded at 5×104 cells per ml were cultured for 7 days in RPMI supplemented with 1% serum in the presence of either 300μM (2R)-Octyl-α-hydroxyglutarate, 5μM IACS-010759, the combination of both or DMSO control. The ratio of live DAPI-positive cells to CountBright™ Absolute Counting Beads were determined on days 3, 5, and 7 using the BD FACSCanto™II flow cytometry system. |
Reaction Conditions | 300μM; 7 days |
Applications | (2R)-Octyl-α-hydroxyglutarate does not induce elevated (R)-2-hydroxyglutarate levels in THP1 cells. |
References: | |
| Cas No. | 1391194-67-4 | SDF | |
| 别名 | (2R)-辛基-Α-羟基戊二酸酯,(2R)-Octyl-2-HG | ||
| Canonical SMILES | O=C(OCCCCCCCC)[C@H](O)CCC(O)=O | ||
| 分子式 | C13H24O5 | 分子量 | 260.33 |
| 溶解度 | DMSO : 100 mg/mL (384.13 mM) | 储存条件 | Store at -20°C |
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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 |
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| % DMSO % % Tween 80 % saline | ||||||||||
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Quality Control & SDS
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- Purity: >97.00%
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