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Screening and identification of the upregulators of ATP-binding cassette transporter A1
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- Author:
- No author available
- Journal Title:
- Acta Pharmaceutica Sinica
- Issue:
- 4
- DOI:
- No doi available
- Key Word:
- ABCA1;上调剂;动脉粥样硬化;高通量筛选
Abstract： 人ATP结合盒转运体A1 (ATP-binding cassette transporter A1,ABCA1)可介导细胞内磷脂和游离胆固醇转运至贫脂或无脂的载脂蛋白A-I (apolipoprotein A-I,apoA-I),从而促进高密度脂蛋白(high density lipoprotein,HDL)生成,启动胆固醇逆转运过程,在机体清除多余脂质的过程中发挥重要作用.因此,本研究以ABCA1为靶点,前期建立了ABCA1上调剂抗动脉粥样硬化(atherosclerosis,AS)药物筛选模型,以期寻找具有新作用机制的抗AS药物.在此研究中,利用该模型对1 600个化合物进行筛选,发现2030421B上调活性大于50％,其EC50为0.50 μg?mL-1.进一步研究发现,2030421B不仅能上调ABCA1的mRNA以及蛋白水平,而且能使小鼠巨噬细胞RAW264.7内胆固醇流出增加,脂滴量减少,是具有较好效果的ABCA1上调剂.
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