In JoVE (2)
Other Publications (1)
Articles by Anneleen Van Hout in JoVE
一种基于动力学荧光的 Ca2 +动员法, 用于识别 G 蛋白偶联受体激动剂、拮抗器和构调制器 Sandra Claes1, Thomas D'huys1, Anneleen Van Hout1, Dominique Schols1, Tom Van Loy1 1Laboratory of Virology and Chemotherapy, Department of Microbiology and Immunology, Rega Institute for Medical Research, KU Leuven 所描述的细胞检测是为鉴定 CXC 趋化因子受体 4 (CXCR4)-相互作用的代理, 抑制或刺激, 无论是竞争性或 allosterically, 细胞内 Ca2 +释放启动的 CXCR4 激活。
一种基于流式细胞仪的检测方法, 用于识别破坏荧光标记的 CXC 趋化因子配体12到 CXC 趋性因子受体4的化合物 Geert Schoofs1, Anneleen Van Hout1, Thomas D'huys1, Dominique Schols1, Tom Van Loy1 1Laboratory of Virology and Chemotherapy, Department of Microbiology and Immunology, Rega Institute for Medical Research, KU Leuven 本文介绍了一种基于流式细胞术的细胞结合检测方法, 主要用作筛选工具, 用于识别抑制荧光标记为 CXC 趋化因子配体 12 (CXCL12) 的化合物对 CXC 趋化因子受体 4 (CXCR4) 的束缚。
Other articles by Anneleen Van Hout on PubMed
Comparison of Cell-based Assays for the Identification and Evaluation of Competitive CXCR4 Inhibitors PloS One. | Pubmed ID: 28410420 The chemokine receptor CXCR4 is activated by its unique chemokine ligand CXCL12 and regulates many physiological and developmental processes such as hematopoietic cell trafficking. CXCR4 is also one of the main co-receptors for human immunodeficiency virus (HIV) entry. Dysfunction of the CXCL12/CXCR4 axis contributes to several human pathologies, including cancer and inflammatory diseases. Consequently, inhibition of CXCR4 activation is recognized as an attractive target for therapeutic intervention. In this regard, numerous agents modifying CXCR4 activity have been evaluated in in vitro experimental studies and pre-clinical models. Here, we evaluated a CXCL12 competition binding assay for its potential as a valuable initial screen for functional and competitive CXCR4 inhibitors. In total, 11 structurally diverse compounds were included in a side-by-side comparison of in vitro CXCR4 cell-based assays, such as CXCL12 competition binding, CXCL12-induced calcium signaling, CXCR4 internalization, CXCL12-guided cell migration and CXCR4-specific HIV-1 replication experiments. Our data indicated that agents that inhibit CXCL12 binding, i.e. the anti-CXCR4 peptide analogs T22, T140 and TC14012 and the small molecule antagonists AMD3100, AMD3465, AMD11070 and IT1t showed inhibitory activity with consistent relative potencies in all further applied CXCR4-related assays. Accordingly, agents exerting no or very weak receptor binding (i.e., CTCE-9908, WZ811, Me6TREN and gambogic acid) showed no or very poor anti-CXCR4 inhibitory activity. Thus, CXCL12 competition binding studies were proven to be highly valuable as an initial screening assay and indicative for the pharmacological and functional profile of competitive CXCR4 antagonists, which will help the design of new potent CXCR4 inhibitors.