trans-translation

MBX-4132, inhibit trans translation by binding to the bacterial ribosome,is a member of a chemical class called oxadiazoles.

PXYC2 is a ribosomal protein S1 (RpsA) antagonist with K ds of 6.35 and 5.11 µM for RpsA-CTD and RpsA-CTD Δ438A, respectively. During the trans-translation process, the ribosomal protein S1 (RpsA) plays a key role [1].

PXYC1 is a ribosomal protein S1 (RpsA) antagonist with Kd values of 0.81 and 0.31 μM for RpsA-CTD and RpsA-CTD Δ438A, respectively. During the trans-translation process of Mycobacterium Tuberculosis (Mtb), RpsA plays a key role [1].

KKL-35 is an inhibitor of trans-translation (IC50: 0.9 µM) with broad-spectrum antibiotic activity.

Lupus autoantigen peptide (LAP), a derivative of the autoantigen La found in systemic lupus erythematosus (SLE) patients, spans amino acids 11-28 of La and functions as an antiviral peptide. It primarily blocks the hepatitis C virus (HCV) from interacting with internal ribosome entry site (IRES) trans-acting factors (ITAFs), notably the polypyrimidine tract-binding protein (PTB) and poly(rC)-binding protein 2 (PCBP2). In a Huh7 cell-based reporter assay, LAP at a concentration of 60 µM effectively hampers HCV IRES-mediated translation, a process reversible by adding recombinant forms of PTB and PCBP2.

PXYC13 is an antagonist of ribosomal protein S1(RpsA). RpsA is essential for the Mycobacterium Tuberculosis(Mtb) trans-translation process. The Kd values of PXYC13 for RpsA-CTD and RpsA-CTD Δ438A is 7.61 and 8.50 μM, respectively [1].

KKL-40 is a small-molecule inhibitor that targets the trans-translation process, effectively suppressing methicillin-sensitive and resistant Staphylococcus aureus (S. aureus) and other Gram-positive pathogens, including vancomycin-resistant Enterococcus faecium, Bacillus subtilis, and Streptococcus pyogenes. It works in synergy with the human antimicrobial peptide LL-37 to inhibit S. aureus, but does not show synergistic effects with other antibiotics such as daptomycin, kanamycin, or erythromycin. KKL-40 inhibits trans-translation, an extreme form of recoding, while being non-toxic to HeLa cells.

IRES-C11 is a specific inhibitor of translation that targets the internal ribosome entry site (IRES) of the c-MYC gene. It functions by blocking the interaction between heterogeneous nuclear ribonucleoprotein A1, a trans-acting factor required for c-MYC IRES activity, and its corresponding IRES. Notably, IRES-C11 does not inhibit the IRES activity of BAG-1, XIAP, and p53.

PXYC12 is an antagonist of ribosomal protein S1(RpsA). RpsA is essential for the trans-translation process in Mycobacterium Tuberculosis (Mtb). The Kd values of PXYC12 for RpsA-CTD and RpsA-CTD Δ438A is 2.67 and 4.67 μM, respectively [1].

ISRIB (trans-isomer) is a potent inhibitor of PERK (IC50=5 nM) that restores protein translation and prevents SG formation in the presence of P-eIF2α.