[Screening and identification of the upregulators of ATP-binding cassette transporter A1].
ATP-binding cassette transporter A1 (ABCA1) promotes cholesterol and phospholipid efflux from cells to lipid-poor apolipoprotein A-I (apoA-I), and plays a key role in the initial steps of the whole process of reverse cholesterol transport (RCT). Upregulation of ABCA1 is beneficial for atherosclerosis (AS) prevention and/or therapy, which indicated that ABCA1 was a target for anti-AS drug development. In the previous study, a high-throughput screening method was established using ABCA1p-LUC HepG2 cell line to find the upregulators of ABCA1. In the present study, compound 2030421B was found using this method, with EC50 of 0.50 microg x mL(-1). The compound was further identified as an upregulator of ABCA1 expression by real-time quantitative reverse transcription-polymerase chain reaction (RT-PCR) and Western blotting analysis. Studies also showed that the 2030421B could induce apoA-I-mediated cholesterol efflux and inhibit lipids uptake into mouse peritoneal macrophages RAW264.7.
National Center for Drug (Microbiology) Screening Laboratory, Institute of Medicinal Biotechnology, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing 100050, China.
Yan-Ni
YN
Xu
Jie
J
Gao
Yang
Y
Xu
Ji-Kai
JK
Liu
Fang-Fang
FF
Lai
Ye-Xiang
YX
Wu
Bin
B
Hong
Shu-Yi
SY
Si
D064286:ATP Binding Cassette Transporter 1; D018528:ATP-Binding Cassette Transporters / Q000235:genetics / Q000378:metabolism*; D000818:Animals; D000924:Anticholesteremic Agents / Q000008:administration & dosage / Q000737:chemistry / Q000494:pharmacology*; D016632:Apolipoprotein A-I / Q000378:metabolism*; D001547:Benzaldehydes / Q000008:administration & dosage / Q000737:chemistry / Q000494:pharmacology*; D001692:Biological Transport; D002478:Cells, Cultured; D002784:Cholesterol / Q000378:metabolism*; D004305:Dose-Response Relationship, Drug; D056945:Hep G2 Cells; D057166:High-Throughput Screening Assays; D006801:Humans; D050356:Lipid Metabolism; D008055:Lipids / Q000032:analysis; D017737:Macrophages, Peritoneal / Q000166:cytology / Q000378:metabolism; D051379:Mice; D015394:Molecular Structure; D012333:RNA, Messenger; D015854:Up-Regulation / Q000187:drug effects
C582745:4-(2-(2-methoxyethoxy)ethoxy)benzaldehyde; C577836:ABCA1 protein, human; D064286:ATP Binding Cassette Transporter 1; D018528:ATP-Binding Cassette Transporters; D000924:Anticholesteremic Agents; D016632:Apolipoprotein A-I; D001547:Benzaldehydes; D008055:Lipids; D012333:RNA, Messenger; D002784:Cholesterol