School of Biomedical Sciences, Faculty of Medicine, The Chinese University of Hong Kong , Shatin, Hong Kong SAR, China.
J Chem Inf Model. 2014 Nov 24;54(11):3046-50. doi: 10.1021/ci500503b. Epub 2014 Nov 4.
We first identified fluorescein, ketazolam, antrafenine, darifenacin, fosaprepitant, paliperidone, risperidone, pimozide, trovafloxacin, and levofloxacin as inhibitors of fatty acid binding protein 4 using molecular docking screening from FDA-approved drugs. Subsequently, the biochemical characterizations showed that levofloxacin directly inhibited FABP4 activity in both the in vitro ligand displacement assay and cell-based function assay. Furthermore, levofloxacin did not induce adipogenesis in adipocytes, which is the major adverse effect of FABP4 inhibitors.
我们首先通过从 FDA 批准的药物中进行分子对接筛选，鉴定出荧光素、卡唑兰、安他非宾、达非那新、福沙匹坦、帕利哌酮、利培酮、匹莫齐特、曲伐沙星和左氧氟沙星为脂肪酸结合蛋白 4 的抑制剂。随后，生化特性分析表明，左氧氟沙星在体外配体置换测定和基于细胞的功能测定中直接抑制 FABP4 活性。此外，左氧氟沙星不会诱导脂肪细胞发生脂肪生成，这是 FABP4 抑制剂的主要不良反应。
