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Tolcapone

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Chemical Structure| 134308-13-7 同义名 : Ro 40-7592
CAS号 : 134308-13-7
货号 : A207157
分子式 : C14H11NO5
纯度 : 99%+
分子量 : 273.241
MDL号 : MFCD00866569
存储条件：

粉末 Inert atmosphere,2-8°C

液体 -20°C:3-6个月-80°C:12个月
溶解度 :

DMSO: 105 mg/mL(384.28 mM)，配合低频超声助溶，注意：DMSO长时间开封后，会吸水并导致溶解能力下降，请避免使用长期开封的DMSO
动物实验配方：
生物活性
靶点

  • Transferase

    COMT, Ki:30 nM
描述 Catechol-O-methyltransferase (COMT) is an enzyme that inactivates dopamine and other catecholamines by O-methylation. Specifically, COMT plays a critical role in the inactivation and metabolism of dopamine and other catechol compounds. The enzyme reduces a catechol molecule in order to prevent genomic damage through DNA adduct formation or via oxygen radicals produced from the redox cycling of catechols. Tolcapone is a potent, reversible inhibitor of COMT and the only available COMT inhibitor that is permeable across the blood-brain barrier with Ki of 30 nM[3]. In HepaRG cells (human cell-line), tolcapone decreased the ATP content with IC50 of 100 ± 15 μM and was cytotoxic with IC50 of 333 ± 45 μM. This suggested that tolcapone's impairment of mitochondrial ATP production might be related to inhibition of enzyme complexes of the electron transport chain and to uncoupling of oxidative phosphorylation. In vivo, SMS-KCNR xenograft models treated orally with 125 mg/kg Tolcapone every 24 h, resulted in a smaller average tumor of 490 ± 310 mm3 compared to control tumors of 1100 ± 450 mm3[4]. The efficacy of tolcapone 200 mg three times daily for 6 months had also been examined in patients with stable Parkinson’s disease (n = 97 - 298), in the longer-term study, the reduction from baseline in the Unified Parkinson’s Disease Rating Scale subscale II score seen with tolcapone was significantly greater than the increase seen with placebo at 6 months (primary endpoint); improvements were maintained after 12 months’ therapy[5].
临床研究
NCT号 适应症或疾病 临床期 招募状态 预计完成时间 地点
NCT02994719 - Recruiting October 2019 United States, Massachusetts ... 展开 >> Clinical Research Center BIDMC Recruiting Boston, Massachusetts, United States, 02215 收起 <<
NCT01158950 Impulsive Behavior Not Applicable Active, not recruiting June 2019 United States, California ... 展开 >> University of California, Berkeley Berkeley, California, United States, 94704 UCSF: Ernest Gallo Clinic and Research Center Emeryville, California, United States, 94591 收起 <<
NCT02260570 Mild Traumatic Brain Injury Not Applicable Recruiting June 29, 2019 United States, California ... 展开 >> VA Northern California Health Care System, Mather, CA Recruiting Sacramento, California, United States, 95655 Contact: Andrew S Kayser, MD PhD    925-372-2059    andrew.kayser@va.gov    Principal Investigator: Andrew S Kayser, MD PhD 收起 <<
实验方案
1mg 5mg 10mg

1 mM

5 mM

10 mM

3.66mL

0.73mL

0.37mL

18.30mL

3.66mL

1.83mL

36.60mL

7.32mL

3.66mL
参考文献

[1]Vieira-Coelho MA, Soares-da-Silva P. Ontogenic aspects of liver and kidney catechol-O-methyltransferase sensitivity to tolcapone. Br J Pharmacol. 1996 Feb;117(3):516-520.

[2]Zurcher G, Keller HH, et al. Ro 40-7592, a novel, very potent, and orally active inhibitor of catechol-O-methyltransferase: a pharmacological study in rats. Adv Neurol. 1990;53:497-503.

[3]Funaki T, Onodera H, Ushiyama N, Tsukamoto Y, Tagami C, Fukazawa H, Kuruma I. The disposition of the tolcapone 3-O-methylated metabolite is affected by the route of administration in rats. J Pharm Pharmacol. 1994 Jul;46(7):571-4. doi: 10.1111/j.2042-7158.1994.tb03859.x. PMID: 7996385.

[4]Maser T, Rich M, Hayes D, Zhao P, Nagulapally AB, Bond J, Saulnier Sholler G. Tolcapone induces oxidative stress leading to apoptosis and inhibition of tumor growth in Neuroblastoma. Cancer Med. 2017 Jun;6(6):1341-1352. doi: 10.1002/cam4.1065. Epub 2017 Apr 21. PMID: 28429453; PMCID: PMC5463066.

[5]Keating GM, Lyseng-Williamson KA. Tolcapone: a review of its use in the management of Parkinson's disease. CNS Drugs. 2005;19(2):165-84. doi: 10.2165/00023210-200519020-00006. PMID: 15697329.