Danirixin

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Chemical Structure| 954126-98-8 同义名 : GSK1325756
CAS号 : 954126-98-8
货号 : A380808
分子式 : C19H21ClFN3O4S
纯度 : 99%+
分子量 : 441.904
MDL号 : MFCD27987922
存储条件：

Pure form Keep in dark place,Sealed in dry,2-8°C

In solvent -20°C:3-6个月-80°C:12个月
溶解度 :

DMSO: 6 mg/mL(13.58 mM)，配合低频超声，并水浴加热至45℃助溶，注意：DMSO长时间开封后，会吸水并导致溶解能力下降，请避免使用长期开封的DMSO
动物实验配方：
生物活性
描述 The CXC chemokine receptor 2 (CXCR2) mediates chemotaxis of leukocytes and controls the extravasation and activation of neutrophils. Danirixin is a small-molecule, selective, and reversible CXCR2 antagonist[2]. Danirixin competes with CXCL8 binding to the membranes prepared from Chinese hamster ovary cells transfected with human CXCR2 or CXCR1 with IC50 values of 12.5nM (pIC50 = 7.90 ± 0.04) and 977nM (pIC50 = 6.03 ± 0.05), respectively. It also acts as a competitive antagonist against CXCL8 in Ca2+ mobilization assays with a Kb of 6.5nM and a pA2 of 8.44. Oral administration of Lewis rats with danirixin at doses of 0.3, 3, and 30mg/kg increased the EC50 value for CXCL2-induced CD11b expression in neutrophils from 4.5nM (the vehicle-treated group) to 9.4, 11.9, and 38.1nM, respectively. In fasted rats following inhaled lipopolysaccharide challenge, danirixin at a dosage of 10 mg/kg led to 84% inhibition of neutrophil influx to the lung with an ED50 value of 1.4mg/kg. In fed rats, 10mg/kg of danirixin resulted in 64% inhibition with an ED50 value of 2.3 mg/kg. Danirixin also dose-dependently inhibited neutrophils when administered to fasted rats 1 hour prior to ozone exposure with an ED50 value of 16.0 mg/kg[3].
实验方案
1mg 5mg 10mg

1 mM

5 mM

10 mM

2.26mL

0.45mL

0.23mL

11.31mL

2.26mL

1.13mL

22.63mL

4.53mL

2.26mL
参考文献

[1]Busch-Petersen J, Carpenter DC, et al. Danirixin: A Reversible and Selective Antagonist of the CXC Chemokine Receptor 2. J Pharmacol Exp Ther. 2017 Aug;362(2):338-346.

[2]Miller BE, Mistry S, Smart K, et al. The pharmacokinetics and pharmacodynamics of danirixin (GSK1325756)--a selective CXCR2 antagonist --in healthy adult subjects. BMC Pharmacol Toxicol. 2015;16:18.

[3]Busch-Petersen J, Carpenter DC, Burman M, et al. Danirixin: A Reversible and Selective Antagonist of the CXC Chemokine Receptor 2. J Pharmacol Exp Ther. 2017;362(2):338-346.