Succinyl phosphonate
目录号 : GC30030
Succinyl phosphonate是一种特异性的α-酮戊二酸脱氢酶（α-KGDHC）抑制剂,在肌肉、细菌、大脑和培养的人成纤维细胞中有效抑制α-KGDHC。
Cas No.:26647-82-5
Sample solution is provided at 25 µL, 10mM.
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Succinyl phosphonate is a specific inhibitor of α -ketoglutarate dehydrogenase (α-KGDHC), effective inhibits KGDHC in muscle, bacterial, brain, and cultured human fibroblasts[1]. α-KGDHC is not only the core enzyme of cellular energy metabolism, but also plays an important role in various physiological processes such as antioxidation and gene expression regulation [2]. Succinyl phosphonate is usually used in the research of the mechanisms of oxidative stress and neuroinflammation in neurodegenerative diseases, such Alzheimer's disease and Parkinson's disease [3][4].
In vitro, treatment of NG108-15 cells with Succinyl phosphonate (0.2mM) for 48h drastically increased the release of LDH induced by glutamate and elevated the levels of resting extracellular glutamate[5].
In vivo, intracerebroventricular injection of Succinyl phosphonate(1mg/kg; 24h) in lipopolysaccharide-induced(LPS-induced) microglia mice down-regulated the succinylation levels, reduced ROS production and improved lipid metabolism, and ameliorated MG senescence[6]. Administration of Succinyl phosphonate(0.02mmol/kg; intranasally; 24h) in rats significantly decreased levels of either citrulline or carnosine and increased the activities of OGDHC and malate dehydrogenase[7].
References:
[1] Biryukov, A. I., Bunik, V. I., Zhukov, Y. N., Khurs, E. N., & Khomutov, R. M. (1996). Succinyl phosphonate inhibits alpha-ketoglutarate oxidative decarboxylation, catalyzed by alpha-ketoglutarate dehydrogenase complexes from E. coli and pigeon breast muscle. FEBS letters, 382(1-2), 167–170.
[2] Tretter, L., & Adam-Vizi, V. (2005). Alpha-ketoglutarate dehydrogenase: a target and generator of oxidative stress. Philosophical transactions of the Royal Society of London. Series B, Biological sciences, 360(1464), 2335–2345.
[3] Trofimova, L., Lovat, M., Groznaya, A., Efimova, E., Dunaeva, T., Maslova, M., Graf, A., & Bunik, V. (2010). Behavioral impact of the regulation of the brain 2-oxoglutarate dehydrogenase complex by synthetic phosphonate analog of 2-oxoglutarate: implications into the role of the complex in neurodegenerative diseases. International journal of Alzheimer's disease, 2010, 749061.
[4] Sayehmiri, F., Khodagholi, F., Pourbadie, H. G., Naderi, N., Aliakbarzadeh, F., Hashemi, R., Naderi, S., & Motamedi, F. (2022). Phosphonate analog of 2-oxoglutarate regulates glutamate-glutamine homeostasis and counteracts amyloid beta induced learning and memory deficits in rats. Experimental gerontology, 168, 111944.
[5] Weidinger, A., Milivojev, N., Hosmann, A., Duvigneau, J. C., Szabo, C., Törö, G., Rauter, L., Vaglio-Garro, A., Mkrtchyan, G. V., Trofimova, L., Sharipov, R. R., Surin, A. M., Krasilnikova, I. A., Pinelis, V. G., Tretter, L., Moldzio, R., Bayır, H., Kagan, V. E., Bunik, V. I., & Kozlov, A. V. (2023). Oxoglutarate dehydrogenase complex controls glutamate-mediated neuronal death. Redox biology, 62, 102669.
[6] Zhao, X., Yang, X., Du, C., Hao, H., Liu, S., Liu, G., Zhang, G., Fan, K., & Ma, J. (2024). Up-regulated succinylation modifications induce a senescence phenotype in microglia by altering mitochondrial energy metabolism. Journal of neuroinflammation, 21(1), 296.
[7] Bunik, V. I., Artiukhov, A. V., Kazantsev, A. V., Aleshin, V. A., Boyko, A. I., Ksenofontov, A. L., Lukashev, N. V., & Graf, A. V. (2022). Administration of Phosphonate Inhibitors of Dehydrogenases of 2-Oxoglutarate and 2-Oxoadipate to Rats Elicits Target-Specific Metabolic and Physiological Responses. Frontiers in chemistry, 10, 892284.
Succinyl phosphonate是一种特异性的α-酮戊二酸脱氢酶（α-KGDHC）抑制剂,在肌肉、细菌、大脑和培养的人成纤维细胞中有效抑制α-KGDHC[1]。α-KGDHC不仅是细胞能量代谢的核心酶，还在抗氧化、基因表达调控等多种生理过程中发挥重要作用[2]。Succinyl phosphonate通常用于通常用于神经退行性疾病如阿尔茨海默病、帕金森病中氧化应激和神经炎症机制的研究[3][4]。
在体外实验中，用0.2mM 的Succinyl phosphonate处理NG108-15细胞48小时，显著增加了谷氨酸诱导的乳酸脱氢酶（LDH）释放，并提高了静息状态下细胞外谷氨酸的水平[5]。
在体内实验中，脂多糖诱导小胶质细胞活化小鼠的脑室内注射Succinyl phosphonate（1mg/kg; 24小时）可下调琥珀酰化水平，减少活性氧（ROS）的产生，改善脂质代谢，并延缓MG衰老[6]。在大鼠中，通过鼻腔给药Succinyl phosphonate（0.02mmol/kg）24小时，显著降低了瓜氨酸或肌肽的水平，并增加了2-氧代戊二酸脱氢酶（OGDHC）和苹果酸脱氢酶的活性[7]。
| Cell experiment [1]: | |
Cell lines | NG108-15 cells |
Preparation Method | Mus musculus neuroblastoma and Rattus norvegicus glioma hybrid cell line NG108-15 was cultured at 37℃ and 5% CO2 in DMEM with 4.5g/L glucose supplemented with 10% FBS and 100IU/ml penicillin and 100μg/ml streptomycin. OGDHC inhibition and activation treatment was introduced to confluent cells (seeding density 0.5 × 105 cells/cm2 ), after allowing a 24h period for attachment. During the attachment and treatment period, supplementation with L-glutamine was omitted in order to prevent endogenous production of glutamate from glutamine. Cells were treated with 5mM glutamate, 1mM TH, 0.5mM NO-donor DETA-NONOate and 0.2mM Succinyl phosphonate over 48h. Cell pellets were collected for determination of viability, OGDHC and PDH activity; culture supernatants were collected for detection of extracellular glutamate concentration and LDH release. |
Reaction Conditions | 0.2mM; 48h |
Applications | Succinyl phosphonate drastically increased the release of LDH induced by glutamate and elevated the levels of resting extracellular glutamate. |
| Animal experiment [2]: | |
Animal models | male mice |
Preparation Method | 2 to 4-month-old male WT mice were injected with injected with LPS 24h after the intracerebroventricular(icv.) injection of Succinyl phosphonate(1mg/kg body weight) in a volume of 2µL. Control mice were injected with body weight corresponding volumes of saline. 24h after the LPS injection, mice were euthanized, and the brains were extracted and were processed for the following experiments. |
Dosage form | 1mg/kg/day for 24h; icv. |
Applications | Succinyl phosphonate down-regulated the succinylation levels, reduced ROS production and improved lipid metabolism, and ameliorated MG senescence. |
References: | |
| Cas No. | 26647-82-5 | SDF | |
| Canonical SMILES | O=C(O)CCC(P(O)(O)=O)=O | ||
| 分子式 | C4H7O6P | 分子量 | 182.07 |
| 溶解度 | Water : ≥ 50 mg/mL (274.62 mM) | 储存条件 | Store at -20°C |
| General tips | 请根据产品在不同溶剂中的溶解度选择合适的溶剂配制储备液；一旦配成溶液，请分装保存，避免反复冻融造成的产品失效。 储备液的保存方式和期限：-80°C 储存时，请在 6 个月内使用，-20°C 储存时，请在 1 个月内使用。 为了提高溶解度，请将管子加热至37℃，然后在超声波浴中震荡一段时间。 |
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| 制备储备液 | |||
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1 mg | 5 mg | 10 mg |
| 1 mM | 5.4924 mL | 27.462 mL | 54.9239 mL |
| 5 mM | 1.0985 mL | 5.4924 mL | 10.9848 mL |
| 10 mM | 0.5492 mL | 2.7462 mL | 5.4924 mL |
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| 给药剂量 | mg/kg |  |
动物平均体重 | g | |
每只动物给药体积 | ul | |
动物数量 | 只 |
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| % DMSO % % Tween 80 % saline | ||||||||||
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工作液浓度： mg/ml；
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2.
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Quality Control & SDS
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- Purity: >98.00%
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