Proteosome inhibitors

Extracellular barriers (DNA, enzymes, mucus) Paucity of receptors Proteosome-mediated degradation Inhibition of second-strand synthesis Airway clearance, anti-inflammatory, anti-protease pre-treatments Alternate serotypes, targeted capsid mutants Proteosome inhibitors (tripeptides, anthracyclines) Tyrosine kinase inhibitors... 

DCI was developed by James C. Powers and coworkers at Georgia Institute of Technology (Harper, J.W., Hemmi, K., and Powers, J.C., Reaction of serine proteases with substituted isocoumarins discovery of 3,4-dichloroisocoumatin, a new general mechanism-based serine protease inhibitor, Biochemistry 24,1831-1841,1985). This inhibitor is reasonably specific, although side reactions have been described. As with the sulfonyl fluorides and DFR the modification is slowly reversible and enhanced by basic solvent conditions and/or nucleophiles. DCI has been used as a proteosome inhibitor. See Rusbridge, N.M. and... 

During the total synthesis of the proteosome inhibitor TMC-95A by S.J. Danishefsky et al., the biaryl moiety of the compound was assembled in good yield by the Suzuki cross-coupling of an aryl iodide and an arylboron intermediate. ... 

First proteosome inhibitor administered as rapid IV bolus twice weekly for 2 weeks in 21-day cycle Increased risk of severe neuropathy in patients with pre-existing neuropathy... 

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