Chemokine receptor antagonists: part 2
EXPERT OPINION ON THERAPEUTIC PATENTS
Authors: Pease, James E.; Horuk, Richard
Abstract
Background: The first part of this two-part review discussed approaches to generating antagonists for some of the CC chemokine receptors, including CCR1, CCR2, CCR3, and CCR4. Objective/method: This second part of the series concludes the review by describing antagonists for CCR5, CCR8, CCR9, CXCR3, CXCR4, and promiscuous antagonists. Conclusion: Chemokine receptor antagonists have found mixed success as therapeutics. Although one antagonist - maraviroc, a CCR5 inhibitor to treat AIDS - has been registered as an approved drug, this is the only success so far. There have been many failures in the clinic and we discuss the idea of promiscuous receptor antagonists as an alternative approach.
I-309 binds to and activates endothelial cell functions and acts as an angiogenic molecule in vivo
BLOOD
Authors: Bernardini, G; Spinetti, G; Ribatti, D; Camarda, G; Morbidelli, L; Ziche, M; Santoni, A; Capogrossi, MC; Napolitano, M
Abstract
Several chemokines have been shown to act as angiogenic molecules or to modulate the activity of growth factors such as fibroblast growth factor 2 (FGF-2) and vascular endothelial growth factor (VEGF). The detection of the CC chemokine receptor (CCR) 8 message in human umbilical vein endothelial cells (HUVECs) by reverse transcription-polymerase chain reaction (RT-PCR) and RNase protection assay (RPA), prompted us to investigate the potential role exerted by the CC chemokine I-309, a known ligand of such receptor, in both in vitro and in vivo angiogenesis assays. We show here that I-309 binds to endothelial cells, stimulates chemotaxis and invasion of these cells, and enhances HUVEC differentiation into capillary-like structures in an in vitro Matrigel assay. Furthermore; I-309 is an inducer of angiogenesis in vivo in both the rabbit cornea and the chick chorioallantoic membrane assay (CAM), (C) 2000 by The American Society of Hematology.