Tolcapone

製品コードS4021 バッチS402101

印刷

化学情報

Chemical Structure Synonyms Ro 40-7592 Storage
(From the date of receipt)		 3 years -20°C powder
1 years -80°C in solvent
化学式

 

C14H11NO5
分子量 273.24 CAS No. 134308-13-7
Solubility (25°C)* 体外 DMSO 55 mg/mL (201.28 mM)
Ethanol 55 mg/mL (201.28 mM)
Water Insoluble
体内 （毎回新しく調製した物を用意してください）
Homogeneous suspension
CMC-NA
≥5mg/ml Taking the 1 mL working solution as an example, add 5 mg of this product to 1 ml of CMC-Na solution, mix evenly to obtain a homogeneous suspension with a final concentration of 5 mg/ml.
* <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 Tolcapone (Ro 40-7592) is a selective, potent and reversible of catechol-O-methyl transferase (COMT) inhibitor with Ki of 30 nM.
in vitro Tolcapone functions as a selective peripheral and central COMT inhibitor, exerting no effect on adrenergic, serotonergic, or cholinergic receptors or other enzymes involved in synthesis or catabolism of catecholamines. [1] This compound produces a concentration-dependent decrease in COMT activity in liver homogenates of developing (3 days-old) and adult (60 days-old) rats with Vmax, Km and IC50 of 5.3 nM/mg/h, 3.3 μM, 41 nM, and 2.9 nM/mg/h, 13.1 μM, 720 nM, respectively. It also produces a concentration-dependent decrease in COMT activity in kidney of developing (3 days-old) and adult (60 days-old) rats with Vmax, Km and IC50 of 2.6 nM/mg/h, 2.7 μM, 8 nM, and 3.5 nM/mg/h, 24 μM, 177 nM, respectively. [2]
in vivo Tolcapone orally administrated is able to crosses the blood-brain barrier. Acute administration of this compound increases basal levels of L-DOPA and dihydroxyphenylacetic acid (DOPAC) and decreases basal homovanillic acid (HVA) levels, but does not affect basal dopamine levels. [3] This compound (30 mg/kg p.o.) combined with benserazide (15 mg/kg p.o.) and a low dose of L-dopa (10 mg/kg p.o.) almost completely blockes (for about 6 h) the formation of 3-O-methyldopa (3-OMD) in brain and plasma, producing a long-lasting increase of L-DOPA in plasma and a parallel marked increase of L-DOPA and dopamine in the brain. [4] It displays behavioural and neurochemical benefits on animals. This chemical (30 mg/kg p.o.) increases the effect of L-DOPA (plus benserazide) on locomotor activity, reserpine-induced hypothermia, and catalepsy induced by pimozide, haloperidol and fluphenazine. It also increases locomotor hyperactivity induced by amphetamine or nomifensine, as well as stereotypy induced by amphetamine (but not apomorphine). [5]

プロトコル(参考用のみ)

キナーゼアッセイ COMT activity assay
COMT activity is evaluated by the ability of homogenates to methylate adrenaline to metanephrine. Aliquots of 0.5 mL of the homogenate are preincubated for 20min with 0.5 mL of phosphate buffer (0.5 mM); thereafter, the reaction mixture is incubated for 30 min with increasing concentrations of adrenaline (5 to 500 μM) in the presence of a saturating concentration (100μM) of the methyl donor (S-adenosyl-L-methionine); the incubation medium contains also pargyline (100 μM), MgCl2 (100 μM) and EGTA (1 mM). The preincubation and incubation are carried out at 37 ℃, in conditions of light protection, with continuous shaking and without oxygenation. In experiments conducted with the aim of studying the inhibitory effect of this compound on COMT activity, homogenates are preincubated for 15 min with increasing concentrations of this chemical (0.5 to 10,000 nM); the incubation is performed in the presence of a concentration of adrenaline three times the corresponding Km value, as determined in saturation experiments. At the end of the incubation period the tubes are transferred to ice and the reaction is stopped by the addition of 100 μL of perchloric acid (2 M). The samples are then centrifuged (200 g, 4 min, 4 ℃), and 500 μL aliquots of the supernatant filtered on microfilters are used for the assay of metanephrine. This procedure allows 99% extraction of catecholamines and their methylated metabolites. The assay of metanephrine is carried out by means of HPLC with electrochemical detection.

参考

  • https://pubmed.ncbi.nlm.nih.gov/2239490/
  • https://pubmed.ncbi.nlm.nih.gov/8821542/
  • https://pubmed.ncbi.nlm.nih.gov/1549240/
  • https://pubmed.ncbi.nlm.nih.gov/2089102/
  • https://pubmed.ncbi.nlm.nih.gov/1977408/

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：

Entacapone alleviates acute kidney injury by inhibiting ferroptosis [ FASEB J, 2022, 36(7):e22399] PubMed: 35691001
Inhibitors of Venezuelan Equine Encephalitis Virus Identified Based on Host Interaction Partners of Viral Non-Structural Protein 3 [ Viruses, 2021, 13(8)1533] PubMed: 34452398
Differential Interactome Based Drug Repositioning Unraveled Abacavir, Exemestane, Nortriptyline Hydrochloride, and Tolcapone as Potential Therapeutics for Colorectal Cancers [ Front Bioinform, 2021, 1:710591] PubMed: 36303724

長期の保管のために-20°Cの下で製品を保ってください。

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。

各々の製品のための特定の保管と取扱い情報は、製品データシートの上で示されます。大部分のSelleck製品は、推薦された状況の下で安定です。製品は、推薦された保管温度と異なる温度で、時々出荷されます。長期の保管のために必要とされてそれと異なる温度で、多くの製品は、短期もので安定です。品質を維持するが、夜通しの積荷のために最も経済的な貯蔵状況を用いてあなたの送料を保存する状況の下に、製品が出荷されることを、我々は確実とします。製品の受領と同時に、製品データシートの上で貯蔵推薦に従ってください。