C-C chemokine receptor type 2 and C-C chemokine receptor type 5 (CCR2/CCR5)

C-C chemokine receptor type 2 (CCR2) and C-C chemokine receptor type 5 (CCR5) are G protein-coupled receptors (GPCRs) that play pivotal roles in the immune system by mediating the migration of leukocytes to sites of inflammation (UniProt P41597, P51681). CCR2 is the primary receptor for monocyte chemoattractant protein-1 (CCL2/MCP-1), driving the mobilization of monocytes from the bone marrow into the circulation, while CCR5 responds to ligands such as CCL5 (RANTES) to facilitate the recruitment of T-cells and macrophages into peripheral tissues (PubMed 29037311). These receptors are significant therapeutic targets due to their involvement in chronic inflammatory conditions, fibrotic diseases like non-alcoholic steatohepatitis (NASH), and infectious diseases (PubMed 31513745). Notably, CCR5 serves as a critical co-receptor for the entry of R5-tropic HIV-1 into host cells (PubMed 8646725). Dual antagonism of CCR2 and CCR5 is a strategic pharmacological approach designed to simultaneously block multiple pathways of leukocyte infiltration, potentially offering synergistic anti-inflammatory and anti-fibrotic effects. Clinical candidates like cenicriviroc have been extensively investigated for their ability to reduce liver fibrosis and inflammation by inhibiting these pathways in patients with metabolic dysfunction-associated steatotic liver disease (PubMed 31513745).

Other names

CD192CD195CKR2CKR5CMKBR2CMKBR5Monocyte chemoattractant protein 1 receptorHIV-1 co-receptor

Dual antagonism of CCR2 and CCR5 receptors to prevent ligand binding and subsequent intracellular signaling, thereby inhibiting leukocyte chemotaxis and tissue infiltration (PubMed 29037311).