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Immunomodulatory imide drugs interactions with cereblon (CRBN) and TNF-α mRNA. IMiDs destabilize the 3′-untranslated region (3′-UTR) of TNF-α mRNA, inhibiting TNF-α protein synthesis and inhibiting inflammatory pathways (Moreira, 1993; Zhu et al., 2003). The glutarimide moiety of the thalidomide backbone catalyzes E3 ubiquitin ligase complex formation, targeting proteins for proteolysis (Chamberlain et al., 2014; Fischer et al., 2014; Petzold et al., 2016; Steinebach et al., 2018).
