Journal
EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY
Volume 51, Issue -, Pages 184-192Publisher
ELSEVIER FRANCE-EDITIONS SCIENTIFIQUES MEDICALES ELSEVIER
DOI: 10.1016/j.ejmech.2012.02.041
Keywords
CXCR7; Ligand; Agonist; 3D fingerprint; beta-arrestin2; Internalization
Categories
Funding
- Dutch Top Institute Pharma [D1.105]
Ask authors/readers for more resources
The chemokine receptor CXCR7 is an atypical G protein-coupled receptor as it preferentially signals through the beta-arrestin pathway rather than through G proteins. CXCR7 is thought to be of importance in cancer and the development of CXCR7-targeting ligands is of huge importance to further elucidate the pharmacology and the therapeutic potential of CXCR7. In the present study, we synthesized 24 derivatives based on a compound scaffold patented by Chemocentryx and obtained CXCR7 ligands with pK(i) values ranging from 5.3 to 8.1. SAR studies were supported by computational 3D Fingerprint studies, revealing several important affinity descriptors. Two key compounds (29 and 30, VUF11207 and VUF11403) were found to be high-potency ligands that induce recruitment of beta-arrestin2 and subsequent internalization of CXCR7, making them important tool compounds in future CXCR7 research. (C) 2012 Elsevier Masson SAS. All rights reserved.
Authors
I am an author on this paper
Click your name to claim this paper and add it to your profile.
Reviews
Recommended
No Data Available