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Inhibition of TLR1/2 dimerization by enantiomers of metal complexes.

We report herein the identification of an immunomodulatory metal-based complex 1 as a direct inhibitor of TLR1/2 heterodimerization. Both enantiomers of complex 1 selectively suppressed TNF-α and TLR1/2 heterodimerization in Pam3CSK4-induced macrophages, with Λ-1 being more potent than Δ-1. Moreover, the complexes inhibited NF-κB transduction via the modulation of TLR1/2 signaling. To our knowledge, complex 1 is the first metal-based inhibitor of TLR1/2 heterodimerization reported to date.