Abstract
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.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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ATP Binding Cassette Transporter 1
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ATP-Binding Cassette Transporters / genetics
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ATP-Binding Cassette Transporters / metabolism*
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Animals
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Anticholesteremic Agents / administration & dosage
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Anticholesteremic Agents / chemistry
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Anticholesteremic Agents / pharmacology*
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Apolipoprotein A-I / metabolism*
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Benzaldehydes / administration & dosage
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Benzaldehydes / chemistry
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Benzaldehydes / pharmacology*
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Biological Transport
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Cells, Cultured
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Cholesterol / metabolism*
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Dose-Response Relationship, Drug
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Hep G2 Cells
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High-Throughput Screening Assays
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Humans
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Lipid Metabolism
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Lipids / analysis
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Macrophages, Peritoneal / cytology
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Macrophages, Peritoneal / metabolism
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Mice
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Molecular Structure
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RNA, Messenger
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Up-Regulation / drug effects
Substances
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4-(2-(2-methoxyethoxy)ethoxy)benzaldehyde
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ABCA1 protein, human
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ATP Binding Cassette Transporter 1
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ATP-Binding Cassette Transporters
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Anticholesteremic Agents
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Apolipoprotein A-I
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Benzaldehydes
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Lipids
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RNA, Messenger
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Cholesterol