DrugBank screening revealed alitretinoin and bexarotene as liver X receptor modulators

被引：43

作者：

Heitel, Pascal ^{[1
]}

Achenbach, Janosch ^{[1
]}

Moser, Daniel ^{[1
]}

Proschak, Ewgenij ^{[1
]}

Merk, Daniel ^{[1
]}

机构：

[1] Goethe Univ Frankfurt, Inst Pharmaceut Chem, Max von Laue Str 9, D-60438 Frankfurt, Germany

来源：

BIOORGANIC & MEDICINAL CHEMISTRY LETTERS | 2017年 / 27卷 / 05期

关键词：

Nuclear receptors; Liver X receptor; Alitretinoin; Bexarotene; SOSA; 9-CIS RETINOIC ACID; NUCLEAR RECEPTOR; LXR-ALPHA; INDOLE-DERIVATIVES; RESPONSE PATHWAY; ADIPOSE-TISSUE; AGONISTS; METABOLISM; CHOLESTEROL; ACTIVATION;

D O I：

10.1016/j.bmcl.2017.01.066

中图分类号：

R914 [药物化学];

学科分类号：

100705 [微生物与生化药学];

摘要：

In silico screening of DrugBank database to detect liver X receptor (LXR) agonism of marketed drugs using a self-organizing map and successive LXR-Gal4 hybrid reporter gene assay evaluation in vitro discovered alitretinoin and bexarotene as partial liver X receptor agonists. Dose-response curves demonstrated that plasma concentrations observed in clinical trials are sufficient for LXR activation and thus could account for LXR-mediated side-effects such as hypercholesterolemia and hyperlipidemia. The discovered drugs are the first reported dual LXR/RXR agonists and can serve as lead structures for LXR and dual LXR/RSR modulator development. (C) 2017 Elsevier Ltd. All rights reserved.

引用

页码：1193 / 1198

页数：6

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