SMG7 Inhibitors

SMG7 inhibitors, as characterized here, are a group of compounds that indirectly alter the function or efficiency of the SMG7 protein within the NMD pathway. These inhibitors work by affecting various cellular processes, such as protein synthesis, mRNA transport, and cell cycle progression, which are all interconnected with the role of SMG7 in the degradation of aberrant mRNA molecules. Leptomycin B and Brefeldin A interfere with nuclear export and Golgi apparatus function, respectively, which are crucial for proper mRNA trafficking and localization. Such disruptions can indirectly impinge upon the NMD process involving SMG7. Proteasome inhibitors like MG132 and Clasto-lactacystin β-lactone can lead to the accumulation of misfolded proteins, triggering cellular stress responses that may affect the NMD pathway and consequently SMG7's activity.

Compounds such as Homoharringtonine, Silvestrol, and Rocaglamide target the initiation phase of protein synthesis, altering the pool of mRNA substrates that SMG7 recognizes and processes. Flavopiridol, by inhibiting cyclin-dependent kinases, can influence cell cycle checkpoints and indirectly modulate the cellular environment in which SMG7 operates. DNA intercalators and crosslinking agents like Mitomycin C and Actinomycin D can alter mRNA synthesis, potentially affecting the range of substrates available for SMG7-mediated NMD. Lastly, Tunicamycin, by inhibiting N-linked glycosylation, can induce endoplasmic reticulum stress, which is known to influence various mRNA decay pathways, including the one mediated by SMG7. These compounds, despite not directly targeting SMG7, can exert considerable influence on its activity by modulating related cellular pathways and processes.