Parameters of pharmacophore hypothesis generation;Parameters of validation and screening;Chemistry;NMR Spectrum of compounds from Ligand-based pharmacophore model for the discovery of novel CXCR2 antagonists as anti-cancer metastatic agents CheJinxin WangZhilong ShengHaichao HuangFeng DongXiaowu HuYouhong XieXin HuYongzhou 2018 Metastatic cancer is considered a fatal progression of cancer worldwide. It has been shown that a key player in this scenario is the CXC chemokine receptor 2 (CXCR2). To identify novel CXCR2 antagonists, a pharmacophore model was built with HipHop program by screening a database containing compounds which were designed based on the known structure–activity relationship (SAR) of the diarylurea series CXCR2 antagonists. Compound <b>1a</b> bearing the novel skeleton was selected from database screening and subjected to the <i>in vitro</i> biological test which resulted in a moderate CXCR2 antagonist potential. With further modification and exploration of SAR, compound <b>1e</b> demonstrated improved CXCR2 antagonist activity with an IC<sub>50</sub> value of 14.8 μM. Furthermore, wound healing assay using the NCI-H1299 cell line indicated that <b>1e</b> showed an excellent anti-cancer metastatic effect (72% inhibition in cell migration at 50 μg ml<sup>−1</sup>).