CMKLR1

CMKLR1 shows wide RNA expression profile but is notably high in plasmacytoid dendritic cells, macrophages, cardiomyocytes, adipocytes and endothelial cells. == Function ==

Activating CMKLR1 by an agonist mobilizes intracellular calcium and causes the activation of several other signaling cascades like the ERK1 and NF-κB. Initial studies of CMKLR1 suggested that it might have a role in the inflammatory pathways. Its cognate ligand, chemerin was found in joint aspirate from rheumatoid arthritis and absent in aspirate from degenerative arthritis. CMKLR1 expression by plasmacytoid dendritic cells and macrophages also helped foster this idea. In vitro chemotaxis assays showed it to be utilized in attracting these cells. As an adipokine receptor it has a role in adipogenesis and adipocyte maturation. It seems also to have a role in peripheral insulin resistance. Also studies using the mouse zymosan model and chemerin peptides showed that these peptides suppressed and helped resolve the peritonitis in mice. The same model showed that this particular molecule enhances macrophage efferocytosis (phagocyting apoptotic cells). == Ligands ==

; Agonists • RvE1 • Navamepent ;Antagonists • CCX832 is an orally active molecule used as a tool compound in experimental pharmacology. It antagonises the effect of CMKLR1. Its chemical structure is undisclosed. The substance was originally developed for use as a pharmaceutical drug against inflammatory diseases by ChemoCentryx, a pharmaceutical firm based in California, in alliance with GlaxoSmithKline (GSK). Development was terminated after a Phase I clinical trial in 2012. • ChemR23-IN-1 • ChemR23-IN-2 • ChemR23-IN-3 • ChemR23-IN-4 • VU0514009 == References ==