syringolin A

Syringolin A is a natural product and member of the syrbactin class of proteasome inhibitors, originally isolated from the plant pathogen *Pseudomonas syringae* pv. *syringae*. It is a cyclic peptide-based molecule that functions as a potent and irreversible inhibitor of the eukaryotic 20S proteasome. Its mechanism of action involves a Michael addition of the catalytic N-terminal threonine residue of the proteasome's active subunits to the α,β-unsaturated carbonyl group within the syringolin ring. This covalent modification specifically targets the chymotrypsin-like activity of the proteasome, leading to the accumulation of misfolded proteins, induction of the unfolded protein response, and subsequent apoptosis and autophagy. Syringolin A has demonstrated significant antiproliferative activity in various cancer models, including neuroblastoma, multiple myeloma, and ovarian cancer, and serves as a lead compound for the development of novel proteasome-targeted anticancer therapies.

Other names

Syringolin A