Institute of Pharmacy/Pharmaceutical Chemistry and Center for Molecular Biosciences Innsbruck, University of Innsbruck , Innrain 80-82, 6020 Innsbruck, Austria.
J Chem Inf Model. 2014 Feb 24;54(2):367-71. doi: 10.1021/ci400682b. Epub 2014 Feb 6.
Agonists of liver X receptors (LXR) α and β are important regulators of cholesterol metabolism, but agonism of the LXRα subtype appears to cause hepatic lipogenesis, suggesting LXRβ-selective activators are attractive new lipid lowering drugs. In this work, pharmacophore modeling and shape-based virtual screening were combined to predict new LXRβ-selective ligands. Out of the 10 predicted compounds, three displayed significant LXR activity. Two activated both LXR subtypes. The third compound activated LXRβ 1.8-fold over LXRα.
肝 X 受体（LXR）α和β的激动剂是胆固醇代谢的重要调节剂，但 LXRα 亚型的激动作用似乎会导致肝脏脂肪生成，这表明 LXRβ 选择性激动剂是有吸引力的新型降脂药物。在这项工作中，结合了药效基团建模和基于形状的虚拟筛选，以预测新的 LXRβ 选择性配体。在所预测的 10 种化合物中，有 3 种显示出显著的 LXR 活性。其中两种激活了两种 LXR 亚型。第三种化合物激活 LXRβ 的活性是激活 LXRα 的 1.8 倍。
