Small molecule specifically inhibiting microglial nitric oxide release could become a potential treatment for neuroinflammation


  • P. Jordan
  • A. Costa
  • E. Specker
  • O. Popp
  • A. Volkamer
  • R. Piske
  • T. Obrusnik
  • S. Kleissle
  • K. Stuke
  • A. Rex
  • M. Neuenschwander
  • J.P. von Kries
  • M. Nazare
  • P. Mertins
  • H. Kettenmann
  • S.A. Wolf


  • PLoS ONE


  • PLoS ONE 18 (2): e0278325


  • Microglia are the immune effector cells of the central nervous system (CNS) and react to pathologic events with a complex process including the release of nitric oxide (NO). NO is a free radical, which is toxic for all cells at high concentrations. To target an exaggerated NO release, we tested a library of 16 544 chemical compounds for their effect on lipopolysaccharide (LPS)-induced NO release in cell line and primary neonatal microglia. We identified a compound (C1) which significantly reduced NO release in a dose-dependent manner, with a low IC50 (252 nM) and no toxic side effects in vitro or in vivo. Target finding strategies such as in silico modelling and mass spectroscopy hint towards a direct interaction between C1 and the nitric oxide synthase making C1 a great candidate for specific intra-cellular interaction with the NO producing machinery.