Structure-based development of antagonists for chemokine receptor CXCR4.
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.
Institute of Functional Nano & Soft Materials and Jiangsu Key Laboratory for Carbon-Based Functional Materials & Devices, Soochow University, Suzhou, Jiangsu, China. yyli@suda.edu.cn
Chongqian
C
Zhang
Tingjun
T
Hou
Zhiwei
Z
Feng
Youyong
Y
Li
D000818:Animals; D019380:Anti-HIV Agents / Q000737:chemistry* / Q000494:pharmacology*; D055808:Drug Discovery / Q000379:methods*; D015658:HIV Infections / Q000188:drug therapy*; D015497:HIV-1 / Q000187:drug effects / Q000502:physiology; D054884:Host-Pathogen Interactions / Q000187:drug effects; D006801:Humans; D062105:Molecular Docking Simulation; D019718:Receptors, CXCR4 / Q000037:antagonists & inhibitors* / Q000737:chemistry / Q000378:metabolism; D053586:Virus Internalization / Q000187:drug effects
D019380:Anti-HIV Agents; D019718:Receptors, CXCR4