Entacapone is a potent, reversible, peripherally acting and orally active inhibitor of catechol-O-methyltransferase (COMT), which effectively inhibits rat liver total COMT with IC50 and Ki values of 20.1nM and 10.7nM, respectively[1]. Entacapone has IC50 values of 14.3nM and 73.3nM for rat liver soluble COMT (S-COMT) and rat liver membrane-bound COMT (MB-COMT), respectively[1]. Entacapone is a weak uncoupler of oxidative phosphorylation[2]. Entacapone is commonly used in combination with levodopa (L-DOPA) to treat Parkinson's disease[3]. Entacapone is a ferroptosis inhibitor that can enhance antioxidant capacity[4].
In vitro, treatment of esophageal cancer cell lines (KYSE-30 and YM-1 cells) with Entacapone (25-150μM) for 48h reduced cell viability in a dose-dependent manner, and induced apoptosis and altered the cell cycle at a concentration of 140μM[5]. Treatment of Hep-G2 cells with Entacapone (50μM) for 48h increased the amount of m6A on mRNA in cells[6].
In vivo, oral treatment of C57BL/6J mice with Entacapone (10, 50, 200mg/kg/day) for 21 days significantly improved ANA-12-induced memory impairment and the reduction of hippocampal brain-derived neurotrophic factor (BDNF) and tyrosine kinase receptor B (TrkB) expression, and significantly increased the number of Ki67-positive proliferating cells, doublecortin-positive immature neurons, and phosphorylated cAMP response element binding protein (pCREB)-positive cells in the dentate gyrus of the hippocampus[7]. Oral treatment of C57BL/6J mice with Entacapone (50mg/kg) for 21 days induced changes in the expression of proteins involved in synaptic transmission, cellular processes, cell signaling, cytoskeletal structure regulation, energy metabolism, and various other cellular responses in the mouse hippocampus[8].
References:
[1] Forsberg M, Lehtonen M, Heikkinen M, et al. Pharmacokinetics and pharmacodynamics of entacapone and tolcapone after acute and repeated administration: a comparative study in the rat[J]. Journal of Pharmacology and Experimental Therapeutics, 2003, 304(2): 498-506.
[2] Nissinen E, Kaheinen P, Penttilä K E, et al. Entacapone, a novel catechol-O-methyltransferase inhibitor for Parkinson's disease, does not impair mitochondrial energy production[J]. European journal of pharmacology, 1997, 340(2-3): 287-294.
[3] Stocchi F, Rascol O, Kieburtz K, et al. Initiating levodopa/carbidopa therapy with and without entacapone in early Parkinson disease: the STRIDE‐PD study[J]. Annals of neurology, 2010, 68(1): 18-27.
[4] Yang J, Sun X, Huang N, et al. Entacapone alleviates acute kidney injury by inhibiting ferroptosis[J]. The FASEB Journal, 2022, 36(7): e22399.
[5] Ramedani F, Jafari S M, Saghaeian Jazi M, et al. Anti‐cancer effect of entacaponeon esophageal cancer cells via apoptosis induction and cell cycle modulation[J]. Cancer Reports, 2023, 6(3): e1759.
[6] Peng S, Xiao W, Ju D, et al. Identification of entacapone as a chemical inhibitor of FTO mediating metabolic regulation through FOXO1[J]. Science Translational Medicine, 2019, 11(488): eaau7116.
[7] Yoo D Y, Jung H Y, Kim W, et al. Entacapone promotes hippocampal neurogenesis in mice[J]. Neural Regeneration Research, 2021, 16(6): 1005-1010.
[8] Yoo D Y, Jung H Y, Kim W, et al. Entacapone treatment modulates hippocampal proteins related to synaptic vehicle trafficking[J]. Cells, 2020, 9(12): 2712.
Entacapone是一种有效的、可逆的、外周作用和具有口服活性的儿茶酚-O-甲基转移酶（COMT）抑制剂，可有效抑制大鼠肝脏总COMT，IC50和Ki值分别为20.1nM和10.7nM[1]。Entacapone对大鼠肝可溶性COMT（S-COMT）和大鼠肝膜结合COMT（MB-COMT）的IC50值分别为14.3nM和73.3nM[1]。Entacapone是一种弱的氧化磷酸化解偶联剂[2]。Entacapone通常与左旋多巴 （L-DOPA）联合使用来治疗帕金森病[3]。Entacapone是一种铁死亡抑制剂，能够增强抗氧化能力[4]。
在体外，Entacapone（25-150μM）处理食管癌细胞系（KYSE-30和YM-1细胞）48h，均剂量依赖性地降低了细胞活力，浓度为140μM时可诱导细胞凋亡并改变了细胞周期[5]。Entacapone（50μM）处理Hep-G2细胞48h，增加了细胞中mRNA上m6A的量[6]。
在体内，Entacapone（10, 50, 200mg/kg/day）通过口服治疗C57BL/6J小鼠21天，显著改善了ANA-12诱导的记忆障碍以及海马脑源性神经营养因子（BDNF）和酪氨酸激酶受体B（TrkB）表达的减少，显著增加了海马齿状回Ki67阳性增殖细胞、双皮质素阳性未成熟神经元和磷酸化cAMP反应元件结合蛋白（pCREB）阳性细胞的数量[7]。Entacapone（50mg/kg）通过口服治疗C57BL/6J小鼠21天，诱导了小鼠海马参与突触传递、细胞过程、细胞信号传导、细胞骨架结构调节、能量代谢和各种其他细胞反应的蛋白质表达变化[8]。