Chemokine-like receptor 1 (CMKLR1) (CMKLR1)

Chemokine-like receptor 1 (CMKLR1), also known as ChemR23 or the Resolvin E1 receptor, is a Class A G protein-coupled receptor (GPCR) that serves as a critical junction between the initiation and resolution phases of inflammation [3, 11, 16]. It is primarily expressed on myeloid cells, including macrophages, dendritic cells, and neutrophils, as well as on adipocytes and vascular smooth muscle cells [5, 10, 13]. CMKLR1 acts as a dual-function receptor: it binds the peptide adipokine chemerin, which typically promotes pro-inflammatory chemotaxis, and the omega-3 fatty acid-derived lipid mediator Resolvin E1 (RvE1), which triggers potent pro-resolving signals [9, 11, 18]. Activation by RvE1 initiates a cascade that inhibits NF-kappaB signaling, reduces pro-inflammatory cytokine production (such as IL-12 and TNF-alpha), and enhances the clearance of apoptotic cells by macrophages through non-phlogistic efferocytosis [2, 6, 18]. CMKLR1 is a promising therapeutic target for chronic inflammatory conditions, including inflammatory bowel disease (IBD), periodontitis, cardiovascular diseases, and metabolic disorders [7, 12, 15, 19]. Unlike traditional anti-inflammatory drugs that suppress the immune system, CMKLR1 agonists aim to actively promote the resolution of inflammation and restore tissue homeostasis [12, 17]. Therapeutic development is currently focused on synthetic Resolvin E1 analogs and small molecule agonists, such as the oral drug candidate TP-317, which is being evaluated in clinical trials for ulcerative colitis and Crohn's disease [1]. Beyond its role in inflammation, CMKLR1's involvement in bone metabolism and adipogenesis suggests a broader role in managing osteoporosis and obesity-related metabolic dysfunction [2, 9, 11].

Other names

ChemR23Resolvin E1 receptorChemerin receptorDEZERV1RVER1Chemerin-like receptor 1

Binding and activation (agonism) of the CMKLR1 receptor to trigger pro-resolving signaling pathways (e.g., NF-kappaB inhibition) and concurrent competitive antagonism of the BLT1 receptor to block pro-inflammatory leukotriene B4 signaling [1, 11, 18].