Discovery of small-molecule inhibitors of the TLR1/TLR2 complex

Angew Chem Int Ed Engl. 2012 Dec 3;51(49):12246-9. doi: 10.1002/anie.201204910. Epub 2012 Sep 11.

Abstract

The protein complex of toll-like receptor 1 and 2 (TLR1/2) is an important regulator of innate immunity, and therefore provides an attractive target for the treatment of various immune disordres. Here we report a novel compound (CU-CPT22) that can compete with the synthetic triacylated lipoprotein (Pam3CSK4) binding to TLR1/2 with high inhibitory activity and specificity. Repression of downstream signaling from TNF-α and IL-1β has also been observed.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Animals
  • Biflavonoids / chemistry*
  • Biflavonoids / pharmacology*
  • Catechin / analogs & derivatives*
  • Catechin / chemistry
  • Catechin / pharmacology
  • Drug Discovery
  • Macrophages / drug effects
  • Macrophages / metabolism
  • Mice
  • Nitric Oxide / antagonists & inhibitors
  • Nitric Oxide / biosynthesis
  • Structure-Activity Relationship
  • Toll-Like Receptor 1 / antagonists & inhibitors*
  • Toll-Like Receptor 1 / chemistry*
  • Toll-Like Receptor 2 / antagonists & inhibitors*
  • Toll-Like Receptor 2 / chemistry*

Substances

  • Biflavonoids
  • Toll-Like Receptor 1
  • Toll-Like Receptor 2
  • benzotropolone
  • Nitric Oxide
  • Catechin