Vipadenant (CEB-4520)(BIIB-014) is an adenosine A2a antagonist with Ki of 1.3 nM; less potent for A1(Ki=69 nM).

A1:69 nM(Ki), A2A:1.3 nM(Ki)

Vipadenant (0.3-30 mg/kg) 以剂量依赖的方式减少猫脑病模型中的僵直。在连续19天的给药方案中，Vipadenant (10 mg/kg) 并未在6-OHDA损伤的大鼠中产生任何统计学上显著的异动症发作[1]。在小鼠及大鼠的氟哌啶醇诱导的运动减缓模型中，Vipadenant的最小有效剂量分别为0.1 mg/kg 和 1 mg/kg。Vipadenant (3 和 10 mg/kg, p.o.) 能增加6-OHDA损伤大鼠的对侧旋转次数[2]。

Peptide substrate phosphorylation assays with GST-Abl kinase domains: The effect of AP24534 (0-320 nM) on GST-Abl kinase activity is assessed by using a synthetic peptide substrate (Abltide: EAIYAAPFAKKK). Assays are carried out at 30 °C for 15 min in 25 μL reaction mixture: 8 mM MOPS (pH 7), 0.2 mM EDTA, 50 μM Abltide, 30 mM MgCl2, 10 mM β-glycerol phosphate, 1 mM EGTA, 0.002% Brij-35, 0.4 mM DTT, 0.2 mg/mL BSA, 0.4 mM sodium orthovanadate, 10 nM WT or mutant GST-Abl kinase, and 100 μM ATP/γ-32[P]ATP (5000 cpm/pmol). Reactions are terminated by transferring a portion of the reaction mixture onto a p81 phosphocellulose filter and immersing in 0.75% phosphoric acid. Filters are washed 3 times in 0.75% phosphoric acid, rinsed in acetone, and air dried; phosphate incorporation is determined by scintillation counting. All results are corrected for background binding to the filters, as determined by omitting peptide substrate from the kinase reaction. Time course experiments to establish the linear range of enzymatic activity precedes kinase assays.