Meldonium

製品コードS4130 バッチS413001

印刷

化学情報

Chemical Structure Synonyms MET-88, Quaterin Storage
(From the date of receipt)		 3 years -20°C powder
1 years -80°C in solvent
化学式

C6H14N2O2
分子量 147.19 CAS No. 76144-81-5
Solubility (25°C)* 体外 Water 29 mg/mL (197.02 mM)
Ethanol 29 mg/mL (197.02 mM)
DMSO Insoluble
* <1 mg/ml means slightly soluble or insoluble.
* Please note that Selleck tests the solubility of all compounds in-house, and the actual solubility may differ slightly from published values. This is normal and is due to slight batch-to-batch variations.

溶剤液（一定の濃度）を調合する

生物活性

製品説明 Meldonium (MET-88, Quaterin) is an inhibitor of biosynthesis of L-carnitine by gamma-butyrobetaine (GBB) hydroxylase and as a competitive inhibitor of renal carnitine reabsorption.
in vitro

Meldonium (40 μM) inhibits the reaction of γ-butyrobetaine hydroxylase with γ-butyrobetaine with Km and Vmax of 36.8 μM and 0.08 nmol/min/mg protein, respectively. [1]
in vivo

Meldonium administered orally to rats for 10 days (150 mg/kg) elicits a reduction in myocardial free camitine and long-chain acyl carnitine content by 63.7 and 74.3%, respectively. Meldonium treatment (100 mg/kg, orally) subsequent administration of isoproterenol results in a reduction in free camitine concentration by 48.7% in comparison with the rats receiving isoproterenol. A prior administration of Meldonium effectively protects the myocardium from isoproterenol-induced variations in the content of ATP and myocardial energy charge, as well as preventing a rise in creatine phosphokinase and lactic dehydrogenase activity. [1] Meldonium  (200 mg/kg) long-term treatment significantly increases the rate of insulin-stimulated glucose uptake by 35% and the expression of glucose transporter 4 (1.7-fold increase), hexokinase II (2.1-fold increase), insulin receptor proteins (2.5-fold increase) and carnitine palmitoyltransferases IA (2.2-fold increase) in mouse hearts. Meldonium long-term treatment statistically significantly decreases fed state blood glucose from 6 to 5 mM. [2] Meldonium reduces the azidothymidine-induced alterations in mouse brain tissue. Meldonium (50 mg/kg) normalizes the increase in caspase-3, cellular apoptosis susceptibility protein (CAS) and iNOS expression. Meldonium also normalizes the changes in cytochromec oxidase (COX) expression, reduces the expression of glial fibrillary acidic protein (GFAP) and cellular infiltration. [3] Meldonium displays protective effects in experimental model of type 2 diabetes in Goto-Kakizaki rats. Meldonium (200 mg/kg) treatment decreases both the fed- and fasted-state blood glucose. Meldonium strongly inhibits fructosamine accumulation and loss of pain sensitivity (by 75%) and also ameliorates the enhanced contractile responsiveness of Goto-Kakizaki rat aortic rings to phenylephrine. In addition, in Meldonium-treated hearts, the necrosis zone following coronary occlusion is significantly decreased by 30%. [4]

プロトコル(参考用のみ)

キナーゼアッセイ γ-Butyrobetaine hydroxylase activity assay
γ-Butyrobetaine hydroxylase activity is assessed by the amount of carnitine formed from γ-butyrobetaine. Camitine is assayed radiometrically with the aid of camitine acetyltransferase and 14C-acetyl-CoA. The 14C-acetyl carnitine is isolated by ion-exchange chromatography on Dowex 2 × 8 (Cl--form, 200-400 mesh) following enzymatic reactions. The incubation mixture (final volume 125 μL) consists of γ-butyrobetaine (75 μL, 6.65-26.6 μM), Meldonium solution (10 μL, 50-500 μM), 20 μL of ascorbate and α-ketoglutarate mixture (500 μL 37.5 mM sodium ascorbate, 375 μL 25 mM αketoglutarate, 125 μL 1 M potassium phosphate buffer, pH 6.7), 10 μL of γ-butyrobetaine hydroxylase and catalase mixture (150 μL of isolated γ-butyrobetaine hydroxylase solution, -77 mU, 50μL catalase solution -2 mg, 50 μL 100 mM potassium phosphate buffer, pH 6.7, 250 μL H2O), ferrous ammonium sulphate (10μL, 6.25 mM). Following incubation for 30 min at 30 ℃ the samples are supplemented with 25 μL 1.6 M KOH and kept for 20 min at 56 ℃. Then, 35 μL of the neutralising solution are added (1 mL 1 M HEPES acid, 400μL 0.5 M glutathione, 10 μL 100 mM EDTA, 250 μL 2 M H3/sub>PO4, water to 1.75 mL). Following neutralisation the sample should have pH 7.6. After adding 10 μL of l-14C-acetyl-CoA (2 nm, 15 nCi) and 5 μL of camitine acetyltransferase (21 μg protein) the mixture is incubated for 30 min at 30 ℃ and each sample is supplemented with 290 mg of dry Dowex resin 2 × 8 (Cl--form, 200-400 mesh) and 600 μL H2O. The samples are shaken for 10 min, spun down (2000 g × 5 min) and the supematant (0.4 mL), is mixed with Bray’s scintillation fluid (10 mL). Radioactivity is measured in an counter.

Selleckの高級品が、幾つかの出版された研究調査結果（以下を含む）で使われた：

αKG-mediated carnitine synthesis promotes homologous recombination via histone acetylation [ bioRxiv, 2024, 2024.02.06.578742] PubMed: 38370789
CRIP1 suppresses BBOX1-mediated carnitine metabolism to promote stemness in hepatocellular carcinoma [ EMBO J, 2022, 41(15):e110218] PubMed: 35775648
Identification of BBOX1 as a Therapeutic Target in Triple-Negative Breast Cancer [ Cancer Discov, 2020, CD-20-0288] PubMed: 32690540

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人間や獣医の診断であるか治療的な使用のためにでない。

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