Macrocyclic mimetics of the Suppressor of Cytokine Signaling 1 and 3 proteins (SOCS1-SOCS3)

In numerous inflammatory, immune, and oncogenic processes, the Janus kinase (JAK)/signal transducer and activator of transcription (STAT) pathway is selectively upregulated in response to cytokine stimulation.Of particular interest are the endogenous proteins that modulate this pathway: the suppressors of cytokine signaling (SOCS) proteins, which operate via a negative feedback mechanism [1] .Notably, SOCS1 and SOCS3 are downregulated in chronic inflammatory diseases and cancer [2] .In this study, aiming to develop SOCS1 and SOCS3 mimetics, we designed and synthesized cyclic analogues using the CLIPS strategy.This method involves the formation of nonnative bonds between the thiol side chains of cysteines and xylene-based scaffolds [3].