Bindarit (Synonyms: AF 2838)

Bindarit (2-methyl-2-[(1-[phenylmethyl]-1H-indazol-3yl) methoxy] propanoic acid) is a small molecule that is able to prevent the chronicity of inflammation and thus decrease the cytotoxic effects of inflammation as well as inhibit the synthesis of C–C chemokines including CCL2, CCL7, and CCL8. Treatment of Bindarit has been shown to lead to a dramatic reduction of urinary CCL2 and albumin excretion.^[1]

In vitro study indicated that Bindarit selectively inhibited the production of the monocyte chemotactic protein subfamily of CC inflammatory chemokines (MCP-1/CCL2) at the transcriptional level. Other in vitro research also showed that Bindarit exerted a concentration-related neuroprotective activity against both Aβ25-35 and Aβ1-42 toxicity. Specifically, in cultures of mixed cortical neural cells, Bindarit reduced Aβ-related neurotoxicity in a dose-dependent manner. This effect correlated with CCL2 suppression at both mRNA and protein level.^[2]

In vivo study demonstrated that Bindarit limited MCP-1/CCL2 upregulation in the kidney of PCK rats and that inhibition of the chemotactic signal translated in a reduced accumulation of inflammatory cells in the kidney. In vitro studies in murine podocytes exposed to albumin overload were instrumental to establish that amelioration of podocyte structure and antiproteinuric effect by Bindarit in PCK rats could be ascribed to drug’s ability of inhibiting podocyte MCP-1/ CCL2 production.^[3]

References:
[1]. Shen Z, et al. Inhibition of CCL2 by Bindarit alleviates diabetes-associated periodontitis by suppressing inflammatory monocyte infiltration and altering macrophage properties. Cell Mol Immunol. 2021 Sep;18(9):2224-2235.
[2]. Severini C, et al. Bindarit, inhibitor of CCL2 synthesis, protects neurons against amyloid-β-induced toxicity. J Alzheimers Dis. 2014;38(2):281-93.
[3]. Zoja C, et al. Effects of MCP-1 inhibition by Bindarit therapy in a rat model of polycystic kidney disease. Nephron. 2015;129(1):52-61.