Screening of CCR4 antagonist and its pharmacodynamics study of anti-inflammation
会议名称：《第三届中日双边药理学和临床药理学学术会议》
会议日期：2007年
学科分类：1007[医学-药学(可授医学、理学学位)] 1006[医学-中西医结合] 100706[医学-药理学] 100602[医学-中西医结合临床] 10[医学]
关 键 词：CCR4 antagonist screening anti-inflammation phannacodynamics
摘 要：AIM To establish a cell-based assay for CCR4 antagonist screening and its pharmacodynamics study of anti-inflammation in *** The hu- man PCDI-CCR4 plasmid was transfected in HEK-293 *** cell line over-expressing CCR4 was selected with G418 and identified by Western blotting analysis and immunofluorescence *** assay condition was opti- mized with FITC labeled CCR4 ligand CKLF1,a novel hu- man chemokine isolated from PHA-stimulated U937 cells. The compounds were screened by fluorescence *** anti-inflammatory pharmacodynamics study of CCR4 antag- onist was further evaluated in *** We have generated a stable cell line and reliable functional assay for CCR4 antagonist *** incubation time was 50 min,the concentration of FITC-CKLF1 was 0.16 g· L,and the cell number per cell was *** the 1080 compounds tested,IMMLG-190 exhibited strong binding to CCR4 (IC=25.4 nmol·L) and inhibited the calci- um transient stimulated by *** IMMLG-190 inhibited the amount of pleural cavity effusion and the in- crease in PGE content in rats induced by an intrapleural injection of *** This technolo- gy can be optimized for high throughput screening and suc- cessfully applied to identify antagonist for *** IMMLG-190 exhibited the protective effect on acute pleu- ral effusion.