Bindarit

Description

Bindarit is an inhibitor of monocyte chemoattractant protein (MCP) production that is selective for MCP-1/CCL2, MPC-3/CCL7, and MCP-2/CCL8 over other chemokines. It inhibits LPS- or C. albicans-induced production of MCP-1/CCL2 in isolated human monocytes (IC₅₀s = 172 and 403 μM, respectively). Bindarit downregulates NF-κB signaling and prevents p65 and p65/p50-mediated MCP-1/CCL2 promoter activation in RAW264.7 cells. It delays the onset of proteinuria and prolongs survival in a mouse model of experimental lupus nephritis when administered at a dose of 50 mg/kg. It prevents LPS-induced increases in MCP-1/CCL2 expression in mouse brain and spinal cord when administered at a dose of 200 mg/kg and reduces the incidence and severity of experimental autoimmune encephalomyelitis (EAE) in mice. Bindarit is also a noncompetitive inhibitor of monocarboxylate transporter 4 (MCT4; K_i = 30.2 μM for the human transporter) that is selective for MCT4 over MCT1.

Uses

Bindarit shows anti-inflammatory activity due to a selective inhibition of a subfamily of inflammatory chemokines. Bindarit is a also protein antidenaturant agent. Bindarit modulates the NFkB pathway and has been shown to reduce secondary phase of adjuvant arthritis in rats.

Uses

Bindarit exhibits selective inhibition against monocyte chemotactic proteins MCP-1/CCL2, MCP-3/CCL7 and MCP-2/CCL8.

in vivo

References

[1] MASSIMILIANO MIROLO. Impact of the anti-inflammatory agent bindarit on the chemokinome: selective inhibition of the monocyte chemotactic proteins.[J]. European cytokine network, 2008, 19 3: 119-122. DOI: 10.1684/ecn.2008.0133
[2] M SIRONI. A small synthetic molecule capable of preferentially inhibiting the production of the CC chemokine monocyte chemotactic protein-1.[J]. European cytokine network, 1999, 10 3: 437-442.
[3] EUGENIO MORA. Bindarit: an anti-inflammatory small molecule that modulates the NFκB pathway.[J]. Cell Cycle, 2012, 11 1: 159-169. DOI: 10.4161/cc.11.1.18559
[4] CARLA ZOJA. Bindarit retards renal disease and prolongs survival in murine lupus autoimmune disease[J]. Kidney international, 1998, 53 3: Pages 726-734. DOI: 10.1046/j.1523-1755.1998.00804.x
[5] SHUJUN GE. The CCL2 synthesis inhibitor bindarit targets cells of the neurovascular unit, and suppresses experimental autoimmune encephalomyelitis.[J]. Journal of Neuroinflammation, 2012: 171. DOI: 10.1186/1742-2094-9-171
[6] YUYA FUTAGI . Identification of a selective inhibitor of human monocarboxylate transporter 4[J]. Biochemical and biophysical research communications, 2018, 495 1: Pages 427-432. DOI: 10.1016/j.bbrc.2017.10.025