LARP4 Inhibitors

Chemical inhibitors of LARP4 function mainly by disrupting various stages of the mRNA translation process, which is integral to the protein's role in mRNA stabilization and poly(A) tail length regulation. Blebbistatin, by inhibiting non-muscle myosin II, affects cytoskeletal rearrangements that are necessary for the proper functioning of LARP4 in translation initiation. Latrunculin A contributes to this disruption by binding to actin monomers, preventing their polymerization and consequently impacting the actin dynamics essential for LARP4-associated mRNA stability. Paclitaxel, on the other hand, hyperstabilizes microtubules, potentially interfering with microtubule-dependent processes that LARP4 might utilize for its role in mRNA translation and stability. Rocaglamide and Silvestrol exert their effects by inhibiting the activity of eukaryotic initiation factor 4A (eIF4A), which is necessary for the mRNA translation process in which LARP4 is involved. This inhibition can impair LARP4's function in the translation machinery.

Furthermore, Homoharringtonine and Harringtonine target the elongation phase of protein synthesis, where Homoharringtonine disrupts the alignment of aminoacyl-tRNAs with the ribosomal A site, and Harringtonine blocks the peptidyl transferase reaction, both leading to an inhibition of the protein synthesis process that involves LARP4. Cycloheximide impedes the translocation step in protein synthesis on eukaryotic ribosomes, thereby potentially inhibiting the elongation process crucial for LARP4's function. Emetine brings about its inhibitory action by blocking ribosomal movement along mRNA, which is a fundamental step in the translation process where LARP4 is implicated. Puromycin causes premature termination of the growing polypeptide chain, which can disrupt mRNA translation and consequently LARP4's function in mRNA stabilization. Anisomycin inhibits peptidyl transferase on the 60S ribosomal subunit, which is essential for LARP4's function in translation. Lastly, Sordarin impedes the function of eukaryotic elongation factor 2 (eEF2), essential for the translocation of ribosomes along mRNA, thereby affecting the translation process in which LARP4 is involved.