A small synthetic molecule capable of preferentially inhibiting the production of the CC chemokine monocyte chemotactic protein-1

Eur Cytokine Netw. 1999 Sep;10(3):437-42.

Abstract

Blocking chemokine production or action is a major target for pharmacological intervention in different human diseases. Bindarit (2-methyl-2-[[1-(phenylmethyl)-1H-indazol-3yl]methoxy]propan oic acid) dose-dependently inhibited MCP-1 and TNF-alpha production induced in vitro in monocytes by LPS and Candida albicans. It did not affect the production of the cytokines IL-1, IL-6, or the chemokines IL-8, MIP-1alpha and RANTES. In the air pouch model in mice, oral treatment reduced monocyte recruitment and local MCP-1 production, induced by carrageenan or IL-1 injection. In NZB/W mice, a model of lupus nephritis, oral treatment prolonged survival and delayed the onset of proteinuria. The results presented here show that bindarit is a preferential inhibitor of the production of MCP-1 in vitro and in vivo and suggest that its beneficial effects in models of joint and kidney inflammation are related to its anti-MCP-1 action. It is therefore possible to selectively and differentially regulate chemokines by targeting their production with small synthetic molecules.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Cell Line
  • Chemokine CCL2 / antagonists & inhibitors*
  • Chemokine CCL2 / biosynthesis
  • Chemokines / biosynthesis
  • Cytokines / biosynthesis
  • Female
  • Humans
  • Indazoles / pharmacology*
  • Mice
  • Monocytes / drug effects
  • Monocytes / metabolism
  • Propionates / pharmacology*

Substances

  • Chemokine CCL2
  • Chemokines
  • Cytokines
  • Indazoles
  • Propionates
  • bindarit