FP7 and FP12, Two Synthetic Toll-like Receptor Antagonists, Do Not Cause Adverse Effects in Mice

Toll-like receptor 4 (TLR4) is a pattern-recognition receptor that detects lipopolysaccharides (LPSs) from Gram-negative bacteria, triggering innate immune and inflammatory responses. Research into TLR4 antagonists and agonists is crucial for developing novel therapies to modulate immune responses in infectious, inflammatory, and autoimmune diseases. Accordingly, some authors of this study developed synthetic TLR4 antagonists, including FP7 and FP12, and demonstrated their efficacy in inhibiting TLR4-mediated effects. This study specifically assesses the safety profile of these two novel TLR4 antagonists in mice following intraperitoneal administration. Clinical signs, body weights, and biochemical and haematological parameters in mice were assessed over four weeks after intraperitoneal administration of these molecules. No mortality or adverse effects were observed after administration of FP molecules. Key circulating biomarkers were also unaffected by these molecules. Preliminary LC–MS analysis detected both compounds in mouse plasma one hour after administration. Overall, this study demonstrates that FP7 and FP12 were well tolerated in mice, with no significant toxicological effects at the tested dose. These findings are an initial step toward further preclinical and clinical development of these molecules.