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。
| 生物活性 | Tolcapone (Ro 40-7592) is a selective, orally active and powerful mixed (peripheral and central)COMTinhibitor with anIC50of 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 toapoptosisand 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 IC50values 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. |
Cell Viability Assay[3] | Cell Line: | NB cell lines: BE(2)-C, SMS-KCNR, CHLA-90, SH-SY5Y, MGT-015-08 and MGT9-102-08 | | Concentration: | 25, 50, 75, 100 μM | | Incubation Time: | | | Result: | A dose-dependent increase in cleaved caspase-3 and cleaved PARP protein in all six NB cell lines and a subsequent decrease in whole caspase-3 and whole PARP protein. |
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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 mm3compared to control tumors of 1100±450 mm3. |
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| 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 |
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| 溶解性数据 | In Vitro: DMSO : 100 mg/mL(365.98 mM;Need ultrasonic) 配制储备液 | 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 |
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