Thiostrepton

BeschreibungThe mammalian transcription factor forkhead box M1 (FoxM1) is induced during G1 phase, with expression continuing through S phase and mitosis. Thiostrepton is a natural peptide thiazole antibiotic that inhibits FoxM1 in mammalian cells, preventing the expression of FoxM1-regulated genes, which includes FoxM1 itself. Through this mechanism, thiostrepton prevents proliferation and induces apoptosis in human cancer cells. These effects correlate with the ability of thiostrepton to act as a proteasome inhibitor.

VerwendenThiostrepton is a macrocyclic antibiotic incorporating thiazoles and other atypical amino acids. Patented in 1961, thiostrepton has been used as an antibiotic and acts by binding to ribosomes to prevent the binding of the EF-G elongation factor and GTP to the 50S ribosomal subunit. Thiostrepton is an inducer of tipA, a gene that controls the bacterial transcription regulators, TipAL and TipAS, that are central regulators in multidrug resistance. Thiostrepton is closely related to siomycin, a recently discovered inhibitor of oncogenic transcription factor, FoxM1.

DefinitionChEBI: A heterodetic cyclic peptide, in which the cyclisation step involves a formal lactonisation between the carboxy group of a quinaldic acid-based residue and a secondary alcohol. An antibiotic that inhibits bacterial protein synthesis. Also acts as an antitu or agent.