Mex67 Inhibitors

Chemical inhibitors of Mex67 can affect its function through various mechanisms, primarily by targeting and inhibiting proteins that interact with or are necessary for the activity of Mex67. For instance, Leptomycin B, Ratjadone, Karyostatin 1A, and Anguinomycin C bind directly to exportin 1 (CRM1), a key protein that Mex67 requires for the nuclear export of messenger RNA (mRNA). By inhibiting CRM1, these chemicals effectively disrupt the CRM1-Mex67 complex, preventing Mex67 from fulfilling its role in transporting mRNA from the nucleus to the cytoplasm. Another compound, Goniothalamin, can interfere with Mex67 by binding to it and potentially altering its conformation, thereby impeding its ability to bind to mRNA and other associated export factors.

Further disrupting the Mex67-mediated mRNA export pathway, Emetine and Mitoxantrone act indirectly by inhibiting the synthesis of proteins that are crucial for Mex67's function. Emetine reduces protein synthesis generally, which includes the synthesis of CRM1, while Mitoxantrone interferes with DNA transcription, which would lead to a decrease in CRM1 production. In addition, Elaiophylin targets the protein VCP/p97, which has roles in mRNA transport; by inhibiting VCP/p97, the transport of mRNA that relies on Mex67 could be affected. LMB-100, while not directly targeting Mex67, may disrupt the nuclear export of various RNA-binding proteins, including Mex67. PKR Inhibitor maintains the translation of proteins essential for mRNA export by preventing PKR-induced inhibition of translation initiation, thus ensuring the availability of Mex67's cofactors. Conversely, Shikonin inhibits the phosphorylation of proteins necessary for the optimal function of Mex67 in mRNA export. Lastly, NSC 617145, by disrupting WEE1 kinase and affecting cell cycle progression, can indirectly affect Mex67's role in mRNA export, as the cell cycle influences the nuclear export processes. Each of these chemicals, through their unique interactions with proteins involved in the Mex67 pathway, can contribute to the inhibition of Mex67's function in mRNA export.