Small-molecule inhibitor: MLN519
Name
- Common name
- MLN519
- Other names
- PS-519
Inhibition
- History
- MLN519 was described as a highly active analogue of clasto-lactacystin beta-lactone by Soucy et al. (1999).
- Peptidases inhibited
- Inhibits particularly the chymotrypsin-like activity of the proteasome, but inhibition of some other peptidases is possible, as by clasto-lactacystin beta-lactone.
- Mechanism
- Inhibition is irreversible, by covalent reaction with the threonine N-terminal nucleophile.
- Pharmaceutical relevance
- PS-159 has been submitted to clinical trials for cerebral ischaemia (Shah et al., 2002) and reperfusion injury (Elliott et al., 2003).
Chemistry
- Structure
![[MLN519 (T01.012 inhibitor) structure ]](/merops/smi/structures/ps519.gif)
- Chemical/biochemical name
- 1R-[1S,4R,5S]-1-(1->hydroxy-2-methylpropyl)-4-propyl-6-oxa-2-azabicyclo[3.2.1.]heptane-3,7-dione; 1R-[1S,4R,5S]-1-(1-hydroxy-2-methylpropyl)-4-propyl-6-oxa-2-azabicyclo[3.2.1.]heptane-3,7-dione
- Related inhibitors
- clasto-lactacystin beta-lactone
Properties
- Synthesis
- Soucy et al. (1999)
General
- Reviews
- Elliott et al. (2003)
