Thiopeptides hold considerable clinical potential , as evidenced by Thiostrepton's use in veterinary medicine as a topical ointment. However, poor solubility has restricted their application in human-use drugs . Thiopeptides are attractive scaffolds to develop novel antibiotics thanks to their potent activity against key cellular processes. Thiopeptides bearing a 26-membered macrocyclic core (e.g., Thiostrepton, Micrococcin peptides) bind the ribosomal protein L11 and the 23S rRNA with high affinity [172](Thiostrepton-bound structure shown in Figure ), effectively blocking the binding of the elongation factor EF-G . Notably, these thiopeptides act on highly conserved bacterial structures [177] while sparing eukaryotic ribosomes [178], minimizing toxicity. Some thiopeptides, including GE2270 and other 29-membered macrocycles, act by inhibiting the ternary complex formation of EFTu-GTP-tRNA, leading to similar effects on bacterial protein synthesis .