Development of a Lactam-Bridged Peptide as Interleukin-11 Antagonist for Renal Fibrosis Treatment.

In recent years, the role of interleukin-11 (IL-11) in renal fibrosis has garnered considerable interest and is regarded as a promising therapeutic target for this condition. Herein, we explored the effects of replacing the oxidation-sensitive thioether moiety with a lactam bridge. By screening linker length and performing further optimization, we developed an analog, 4L6-16. This compound exhibited a high binding affinity for IL-11, with a KD value of 134 nM, along with enhanced antagonistic activity. Moreover, 4L6-16 demonstrated significant renoprotective effects in both in vitro and in vivo models of renal fibrosis, supporting its potential for further optimization to develop novel IL-11-targeted therapeutic agents.