AF10847 – Other Categories

Activation of the inflammatory response is critical to various infectious agents. Pro-inflammatory cytokines like-IL-1α and IL-1β are upregulated upon the initial detection of infection and bind to IL-1R1 to activate the signalling cascade. However, a hyperinflammatory response can lead to oxidative stress, apoptosis, and conditions such as diabetes, rheumatoid arthritis, cancer, and ischemia. To maintain homeostasis there are moderators of the inflammatory response. Binding of interleukin IL-1 to IL-1R1 stimulates the inflammatory cascade. Alternately, AF10847 binds to IL-1R1 resulting in significant conformational change of IL-1R1 but its lack of any cytokine activity locks IL-1R1 in an inactive state inhibiting a signalling event. AF10847 has an exceedingly high affinity for IL-1R1 compared to 1α and IL-1β. Extensive searches for lower molecular mass IL-1R antagonists-for oral delivery as a therapeutic for rheumatoid arthritis are being carried out. AF10847 is a 21-mer that has high affinity for the conserved IL-1R1 binding site that is also recognised by IL-1β. The remarkable high affinity of AF10847 for IL-1R1 makes it a perfect candidate for further investigations into novel IL-1R1 inhibitor development.