生物活性

• 描述The A2B adenosine receptor is a G protein-coupled receptor that belongs to the four member family of adenosine receptors: A1, A2A, A2B, A3. The activity of the A2B adenosine receptor is mediated by G proteins which activate adenylyl cyclase, and it stimulates adenylate cyclase activity in the presence of adenosine. This protein also interacts with netrin-1, which is involved in axon elongation. BAY -545 is a potent and selective A2B adenosine receptor antagonist. In a high-throughput screening procedure measuring clytin luminescence, the IC50 of BAY-545 against human A2B adenosine receptor was 59 nM. According to alternative radioligand displacement assays, BAY-545 exhibited IC50s of 66, 400, 280 nM for human, mouse, rat A2B adenosine receptor in cells, respectively, and a Ki of 97 nM for human A2B adenosine receptor, with more selectivity over A1, A2A, and A3 adenosine receptors^[2]. In ELISA assay to measure the release of IL-6 from human fibroblast LL29 cells incubated with BAY-545 for 24h, it was reported that BAY-545 inhibited NECA induced release of IL-6 with an IC50 of 185 nM ^[2]. In a FITC-induced pulmonary fibrosis model in mice, BAY-545 orally administrated at 100 or 500 mg/kg twice a day for 3 days significantly reduced Osteopontin in bronchoalveolar lavage fluid (BALF) compared to placebo group, and BAY-545 at the dose of 500 mg/kg significantly reduced relative lung weight, IL-6 level in the lung tissue homogenate and cell counts in BALF compared to placebo. In a silica-induced pulmonary fibrosis model in mice, BAY-545 orally administrated at 100 or 500 mg/kg twice a day for 7 days significantly reduced TGF-β1 level in the lung tissue homogenate compared to placebo group, and BAY-545 at the dose of 500 mg/kg significantly reduced relative lung weight compared to placebo^[2].

• 动物研究
  剂量	Mice: 100 mg/kg - 500 mg/kg[2] (p.o.)
  给药途径	p.o.
  动物药代数据	Animal Mice[2] Rats[2] Dogs[2] Dose 0.3 mg/kg (i.v.) 1 mg/kg (p.o.) 0.3 mg/kg (i.v.) 1 mg/kg (p.o.) 0.3 mg/kg (i.v.) 1 mg/kg (p.o.) Administration i.v. p.o. i.v. p.o. i.v. p.o. MRT 0.65 h (i.v.) 1.2 h (p.o.) 1.3 h (i.v.) 2.0 h (p.o.) 1.3 h (i.v.) 4.4 h (p.o.) F 65% (p.o.) 88% (p.o.) 79% (p.o.) T1/2 1.2 h (i.v.) 2.1 h (p.o.) 1.4 h (i.v.) 1.4 h (p.o.) 1.4 h (i.v.) 5.1 h (p.o.) AUCnorm 1.6 kg·h/L (i.v.) 1.0 kg·h/L (p.o.) 0.78 kg·h/L (i.v.) 1.0 kg·h/L (p.o.) 2.5 kg·h/L (i.v.) 2.0 kg·h/L (p.o.) CL 0.61 L/h/kg (i.v.) 1.1 L/h/kg (i.v.) 0.4 L/h/kg (i.v.) Cmax, norm 1.2 kg/L (p.o.) 0.33 kg/L (p.o.) 0.61 kg/L (p.o.) Vss 0.4 L/kg (i.v.) 1.5 L/kg (i.v.) 2.0 L/kg (i.v.)