Opicapone-BIA-9-1067-DataSheet-生命科學(xué)試劑-MedChemExpress

1、Hotline: 400-820-3792Inhibitors Agonists Screening Librarieswww.MedChemEOpicaponeCat. No.: HY-14896CAS No.: 923287-50-7Synonyms: BIA 9-1067分式: CHClNO分量: 413.17作靶點: COMT作通路: Metabolic Enzyme/Protease; Neuronal Signaling儲存式: Powder -20C 3 years4C 2 yearsIn solvent -80C 6 months-20C 1 month溶解性數(shù)據(jù)體外實驗 DM

2、SO : 100 mg/mL (242.03 mM; Need ultrasonic)H2O : 40% PEG300 5% Tween-80 45% salineSolubility: 2.5 mg/mL (6.05 mM); Clear solution2. 請依序添加每種溶劑： 10% DMSO 90% (20% SBE-CD in saline)Solubility: 2.5 mg/mL (6.05 mM); Suspended solution; Need ultrasonic1/3 Master of Small Molecules 您邊的抑制劑師www.MedChemEBIOLO

3、GICAL ACTIVITY物活性 Opicapone種每次的、有效的第三代茶酚-O-甲 轉(zhuǎn)移酶e (COMT)抑制劑，于帕森病和運動波動治療。Opicapone 降低細胞 ATP 含量，IC50為 98 M。IC50 & Target COMT 1體外研究 Opicapone has a prolonged inhibitory effect on peripheral COMT, which extends the bioavailability oflevodopa, without inducing toxicity. Opicapone decreases the ATP conte

4、nt of the cells with IC50 values of 98M. Incubation of human primary hepatocytes for 24 h with increasing concentrations of Tolcapone,entacapone or Opicapone resulted in a concentration-dependent decrease in the mitochondrial membranepotential of the cells, evaluated by the ratio JC-1 aggregates ove

5、r JC-1 monomer (ratio ex 544 em 590over ex 485 em 538). Opicapone decreases the mitochondrial membrane potential of the cells with IC50 of181 M 1.體內(nèi)研究 Opicapone inhibits rat peripheral COMT with ED50 values below 1.4 mg/kg up to 6 h post-administration.The effect is sustained over the first 8 h and

6、by 24 h COMT had not returned to control values. A singleadministration of Opicapone resulted in increased and sustained plasma levodopa levels with a concomitantreduction in 3-O-methyldopa from 2 h up to 24 h post-administration, while Tolcapone produced significanteffects only at 2 h post-administ

7、ration. The effects of Opicapone on brain catecholamines after levodopaadministration are sustained up to 24 h post-administration. Opicapone is also the least potent compound indecreasing both the mitochondrial membrane potential and the ATP content in human primary hepatocytesafter a 24 h incubati

8、on period 1.PROTOCOLKinase Assay 1 ATP content of human primary hepatocytes is determined using the ATP Lite assay system, which is basedon the production of light caused by the reaction of ATP with added luciferase and D-luciferin. Twenty-fourhours after being seeded, cell cultures are washed with

9、Hanks balanced salt solution (HBSS) and are thenincubated with test compounds prepared in culture media without fetal bovine serum (0, 1.56, 3.13, 6.25,12.5, 25, 50, 100 and 200 M) for 24 h at 37C in humidified 5% CO2-95% air. Positive controls (cellsincubated with carbonyl cyanide-p-trifluoromethox

10、yphenylhydrazone-FCCP, 10 and 50 M) are run inparallel. After incubation, media are removed from the wells and substituted with 100 L HBSS plus 50 Lcell lysis solution. Plates are shaken for 5 min at 400 r.p.m. at room temperature. Substrate solution (50 L)is then added to each well and plates are a

11、gain shook for 5 min at 400 r.p.m. at room temperature insubdued light. Three standard concentrations of ATP (1, 10 and 100 M) and blanks are run in parallel inplate wells without cells. Plates are dark adapted for 10 min and luminescence is determined on aMicrobetaTriLux scintillation counter 1.MCE

12、 has not independently confirmed the accuracy of these methods. They are for reference only.Animal Rats 1Administration 1 Male Wistar rats (240) are used. In experiments designed to evaluate the efficacy of the compound at2/3 Master of Small Molecules 您邊的抑制劑師www.MedChemEinhibiting COMT, animals are

13、administered Opicapone (0.03, 0.1, 0.3, 0.6, 1, 3 and 10 mg/kg) and are killedat 2 and 6 h post-administration. In experiments designed to evaluate COMT time-activity profile, animals aregiven Opicapone (3 mg/kg) and are killed at different post-administration periods (15 and 30 min, and 1, 2, 4,8,

14、18, 24, and 48 h). In experiments designed to evaluate the effects of the compounds on centralcatecholamines, animals are given 3 mg/kg Opicapone or Tolcapone and 1 h before being killed, animals areadministered levodopa/benserazide (levodopa 12 mg/kg and benserazide 3 mg/kg).MCE has not independent

15、ly confirmed the accuracy of these methods. They are for reference only.REFERENCES1. Bonifcio MJ, et al. Pharmacological profile of Opicapone, a third-generation nitrocatechol catechol-O-methyl transferase inhibitor, in therat. Br J Pharmacol. 2015 Apr;172(7):1739-52.2. Ferreira JJ, et al. Opicapone as an adjunct to levodopa in patients with Parkinsons disease and end-of-dose motor fluctuations: arandomised, double-blind, controlled trial. Lancet