Monocyte chemoattractant protein-1 (MCP-1/CCL2) and other members of the MCP cluster (MCP-2/CCL8 and MCP-3/CCL7) are potent chemotactic cytokines that collaboratively promote inflammation through monocyte-macrophage recruitment. Bindarit is an indazolic derivative that inhibits the expression of CCL2, CCL7, and CCL8, as well as IL-12. It can inhibit LPS- or C. albicans-induced production of CCL2 in human monocytes with IC50 values of 172 and 403 μM, respectively. Bindarit has been shown to downregulate the NF-κB pathway, preventing p65 and p65/p50-mediated CCL2 promoter activation. Through potent suppression of CCL2 transcription, bindarit has been reported to reduce symptoms in several animal models of human inflammatory diseases, including lupus nephritis, arthritis, cancer, and encephalomyelitis.
