Current Computer-Aided Drug Design

Subhash C. Basak
Departments of Chemistry, Biochemistry & Molecular Biology University of Minnesota Duluth
Duluth, MN 55811
USA

Back

Structure-Based Development of Antagonists for Chemokine Receptor CXCR4

Author(s): Chongqian Zhang, Tingjun Hou, Zhiwei Feng, Youyong Li.

Abstract:

The C-X-C chemokine receptor-4(CXCR4) is a G-protein coupled receptor (GPCR) which belongs to the family I GPCR or rhodopin-like GPCR family. CXCR4 plays a crucial role as a co-receptor with CCR5 for HIV-1 anchoring to mammalian cell membrane, and is implicated in cancer metastasis and inflammation. Recently, crystal structure of human CXCR4 receptor was reported, which facilitates the structure-based drug discovery of CXCR4 significantly. Here we summarize the structure feature of C-X-C chemokine and its difference from other rhodopsin-like GPCR family, the impact of recent crystal structure on CXCR4 drug development, the available active compounds for CXCR4 receptor, SAR studies of the available active compounds, the recognition mechanism of the inhibitors of CXCR4 receptor (molecular docking results and molecular dynamics results), which illustrates the interaction between the inhibitors and critical residues of CXCR4, and the outlook of drug development for CXCR4 receptor.

Keywords: CXCR4, crystal structure, anti-HIV-1 inhibitors, DOCK, molecular dynamics, SAR, drug development, critical residues, chemokine receptor, antagonist

Order Reprints Order Eprints Rights & PermissionsPrintExport

Article Details

VOLUME: 9
ISSUE: 1
Year: 2013
Page: [60 - 75]
Pages: 16
DOI: 10.2174/1573409911309010006