Exportin 5 Inhibitors

Exportin 5 inhibitors constitute a diverse class of chemicals that modulate the activity of Exportin 5 through direct or indirect mechanisms. While specific inhibitors directly targeting Exportin 5 are limited, compounds that disrupt shared nuclear export pathways, particularly those involving CRM1 (Exportin 1), indirectly impact Exportin 5 function. Leptomycin B and Leptomycin A directly inhibit Exportin 1, impacting the broader nuclear export machinery and potentially influencing the export of pre-miRNAs by Exportin 5. KPT-330 (Selinexor) and other selective inhibitors of nuclear export (SINE) target XPO1, affecting CRM1-mediated nuclear export and potentially influencing Exportin 5-mediated export of pre-miRNAs.

The compounds like CBS9106, KPT-185, and Ratjadone A also interfere with XPO1, indirectly affecting Exportin 5 by disrupting shared export pathways. Additionally, compounds such as LMB-100 and Valtrate, which are based on Leptomycin B, utilize different delivery mechanisms to impact CRM1 and potentially modulate Exportin 5 function. Chromomycin A3, by binding to G-quadruplex structures in DNA, and 2-Methoxyestradiol, by inhibiting HIF-1α, represent compounds that indirectly influence Exportin 5 by altering the processing and availability of pre-miRNAs. The derivatives of KPT-185 further exemplify the ongoing efforts to enhance the specificity and potency of XPO1 inhibitors, potentially influencing Exportin 5-mediated export of pre-miRNAs. Collectively, these inhibitors provide valuable tools for understanding and manipulating the intricate regulatory mechanisms governing Exportin 5 in cellular processes related to miRNA biogenesis.