Ligand-based pharmacophore model for the discovery of novel CXCR2 antagonists as anti-cancer metastatic agents.

ABSTRACT: 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 the 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 1a bearing the novel skeleton was selected from database screening and subjected to the in vitro biological test which showed a moderate CXCR2 antagonist potential. With further modification and exploration of SAR, compound 1e demonstrated improved CXCR2 antagonist activity with an IC₅₀ value of 14.8 µM. Furthermore, wound healing

SUBMITTER: Che J 

PROVIDER: S-EPMC6083693 | biostudies-literature | 2018 Jul

REPOSITORIES: biostudies-literature