NPT1220-312, a TLR2/TLR9 Small Molecule Antagonist, Inhibits Pro-Inflammatory Signaling, Cytokine Release, and NLRP3 Inflammasome Activation

Figure 3

NPT1220-312 is an allosteric antagonist at TLR2 and TLR9. NPT1220-312 suppressed: (a) Pam₂CSK₄-, (b) Pam₃CSK₄-, and (c) ODN2006-evoked SEAP release (OD655 nm) to the medium in hTLR2 HEK293 cells; (d) the dose-effect curve for an agonist determined in the presence of various concentrations of an antagonist, Schild plots; and (e–g) dose ratios derived from Gaddum analysis of EC₅₀ and IC₅₀ values for (e) Pam₂CSK₄, (f) Pam₃CSK₄, and (g) ODN2006. NPT1220-312 concentration dependently suppressed the maximum TLR2 or TLR9 agonist-evoked responses in a manner consistent with a non-competitive interaction [40].

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