Title:Current Status of SUMOylation Inhibitors
Volume: 28
Issue: 20
Author(s): Christopher M. Brackett and Brian S.J. Blagg*
Affiliation:
- Department of Chemistry and Biochemistry, University of Notre Dame, Notre Dame, Indiana 46556,United States
Keywords:
SUMO, cancer, ubiquitin-like, post-translational modifications, natural products, small-molecules,
enzyme inhibitors.
Abstract: SUMOylation has emerged as an important post-translational modification that involves
the covalent attachment of the Small Ubiquitin-like Modifier (SUMO) polypeptide to a
lysine residue of a target protein. The enzymatic pathway of SUMOylation is very similar to
ubiquitinylation and involves an activating enzyme, a conjugating enzyme, ligases, and deconjugating
enzymes. SUMOylation modulates the function of a number of proteins associated
with various pathways, and in fact, dysregulation of the SUMOylation pathway is observed
in both cancer and neurological diseases. In many cancers, the SUMO enzymes are
upregulated, and SUMO levels correlate directly with prognosis and disease progression. As a
result, there has been an emphasis on the discovery and development of inhibitors of SUMOylation.
In this review, the latest advances in SUMOylation inhibitors are described alongside
the methods used to discover small molecule SUMOylation inhibitors, which include natural
products, peptidomimetics, as well as synthetic derivatives identified via virtual screens.
