Proteasome inhibitor

Mechanism

Examples

• The first non-peptidic proteasome inhibitor discovered was the natural product lactacystin.
• Disulfiram has been proposed as another proteasome inhibitor.
• Epigallocatechin-3-gallate has also been proposed.
• Marizomib has started clinical trials for multiple myeloma.
• Oprozomib, delanzomib have also started clinical trials.
• Epoxomicin is a naturally occurring selective inhibitor.
• MG132 is a synthesized peptide commonly used for in vitro studies.
• Beta-hydroxy beta-methylbutyrate is a proteasome inhibitor in human skeletal muscle in vivo.

  Approved medications

• Bortezomib was approved in 2003. This was the first proteasome inhibitor approved for use in the U.S. Its boron atom binds the catalytic site of the 26S proteasome.
• Carfilzomib was approved by the FDA for relapsed and refractory multiple myeloma in 2012. It irreversibly binds to and inhibits the chymotrypsin-like activity of the 20S proteasome.
• Ixazomib was approved by the FDA in 2015 for use in combination with lenalidomide and dexamethasone for the treatment of multiple myeloma after at least one prior therapy. It is the first orally-available proteasome inhibitor