FBXO42 Inhibitors

FBXO42, a member of the F-box protein family, serves as the substrate recognition component of the Skp1-Cullin-F-box (SCF) E3 ubiquitin ligase complex. It plays a crucial role in the regulation of protein turnover by targeting specific substrates for ubiquitination and subsequent proteasomal degradation. Functionally, FBXO42 contributes to various cellular processes, including cell cycle progression, DNA repair, signal transduction, and apoptosis, by controlling the abundance of key regulatory proteins. Dysregulation of FBXO42 activity has been implicated in the pathogenesis of various diseases, including cancer, neurodegenerative disorders, and inflammatory conditions. The inhibition of FBXO42 involves targeting its ubiquitin ligase activity or modulating the expression of its target substrates. Several chemical inhibitors have been identified that directly interfere with the function of FBXO42, including proteasome inhibitors like MG-132 and Velcade, which lead to the accumulation of FBXO42 substrates and subsequent inhibition of its activity. Additionally, compounds such as Nutlin-3 and MLN4924 disrupt the interaction between FBXO42 and its substrates or inhibit the neddylation of cullin proteins, respectively, thereby preventing substrate ubiquitination and degradation. Indirect inhibition of FBXO42 can also be achieved by down-regulating its expression using inhibitors of transcription or protein synthesis, such as Actinomycin D or Cycloheximide. Overall, understanding the mechanisms of FBXO42 inhibition provides insights into its role in cellular homeostasis and disease pathology, offering potential avenues for intervention in FBXO42-associated disorders.