Tolcapone (Ro 40-7592) 是一种选择性，

Tolcapone  (Synonyms: 托卡朋; Ro 40-7592)

Tolcapone (Ro 40-7592) 是一种选择性，有效的，具有口服活性的外周和中枢 COMT 抑制剂，在肝脏中对 COMT 的 IC₅₀ 为 773 nM。Tolcapone 还是一种 α-syn 和 Aβ42 寡聚和原纤维形成的有效抑制剂。Tolcapone 诱导氧化应激导致神经母细胞瘤细胞凋亡(apoptosis) 和抑制肿瘤生长。

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生物活性    
Tolcapone (Ro 40-7592) is a selective, orally active and powerful mixed (peripheral and central) COMT inhibitor with an IC50 of 773 nM in the liver[1]. Tolcapone is also a potent inhibitor of α-syn and Aβ42 oligomerization and fibrillogenesis[2]. Tolcapone induces oxidative stress leading to apoptosis and inhibition of tumor growth in neuroblastoma[3].

IC50 & Target    
COMT[1]
α-syn and Aβ42 oligomerization, fibrillogenesis[2]

体外研究(In Vitro)    
Tolcapone is cytotoxic to neuroblastoma (NB) cells with IC50 values ranging from 32.27 μM for SMS-KCNR cells to 219.8 μM for MGT9-102-08 primary cells[3].
Tolcapone (25, 50,75, 100 μM) treatment activates downstream apoptotic events in NB cells. Tolcapone induces caspase-mediated apoptosis in neuroblastoma[3].

Cell Viability Assay[3]

Cell Line:    BE(2)-C, SMS-KCNR, CHLA-90, SH-SY5Y, MGT-015-08 and MGT9-102-08
Concentration:    1.5625~400 μM
Incubation Time:    48 hours
Result:    IC50s of 32.27, 72.31, 80.29, 109.4, 174.6, 219.8 μM for SMS-KCNR, SH-SY5Y, BE(2)-C, CHLA-90, MGT-015-08 and MGT9-102-08, respectively.

体内研究(In Vivo)    
Tolcapone (125 mg/kg; orally) inhibits tumor growth and prolongs survival in vivo. There are no adverse events or differences in weight or behavior noted in the mice[3].

Animal Model:    4-week-old female nude mice (nu/nu) bearing SMS‐KCNR xenograft models [3]
Dosage:    125 mg/kg
Administration:    Treated orally every 24 h for 35 days
Result:    Decreased tumor volume compared to control.
Resulted in a smaller average tumor of 490±310 mm3 compared to control tumors of 1100±450 mm3.


分子量    
273.24

性状    
Solid

Formula    
C14H11NO5

CAS 号    
134308-13-7

中文名称    
托卡朋

运输条件    
Room temperature in continental US; may vary elsewhere.

储存方式    
Powder    -20°C    3 years
4°C    2 years
In solvent    -80°C    6 months
-20°C    1 month
溶解性数据    
In Vitro: 
DMSO : 100 mg/mL (365.98 mM; Need ultrasonic)

配制储备液    
浓度溶剂体积质量    1 mg    5 mg    10 mg
1 mM    3.6598 mL    18.2989 mL    36.5979 mL
5 mM    0.7320 mL    3.6598 mL    7.3196 mL
10 mM    0.3660 mL    1.8299 mL    3.6598 mL
*
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, 6 months; -20°C, 1 month。-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。

In Vivo:
请根据您的实验动物和给药方式选择适当的溶解方案。以下溶解方案都请先按照 In Vitro 方式配制澄清的储备液，再依次添加助溶剂：

——为保证实验结果的可靠性，澄清的储备液可以根据储存条件，适当保存；体内实验的工作液，建议您现用现配，当天使用； 以下溶剂前显示的百分比是指该溶剂在您配制终溶液中的体积占比；如在配制过程中出现沉淀、析出现象，可以通过加热和/或超声的方式助溶

1.
请依序添加每种溶剂： 10% DMSO    40% PEG300    5% Tween-80    45% saline

Solubility: ≥ 2.5 mg/mL (9.15 mM); Clear solution

2.
请依序添加每种溶剂： 10% DMSO    90% (20% SBE-β-CD in saline)

Solubility: ≥ 2.5 mg/mL (9.15 mM); Clear solution
 

参考文献

[1]. Catechol-O-methyltransferase: variation in enzyme activity and inhibition by entacapone and tolcapone. C De Santi, et al. Eur J Clin Pharmacol. 1998 May;54(3):215-9.  [Content Brief] [2]. Saviana Di Giovanni, et al. Entacapone and tolcapone, two catechol O-methyltransferase inhibitors, block fibril formation of alpha-synuclein and beta-amyloid and protect against amyloid-induced toxicity. J Biol Chem. 2010 May 14;285(20):14941-14954.  [Content Brief] [3]. Tyler Maser,et al. Tolcapone induces oxidative stress leading to apoptosis and inhibition of tumor growth in Neuroblastoma.Cancer Med. 2017 Jun;6(6):1341-1352.  [Content Brief]