Proteasome inhibitors are drugs that block the action of proteasomes, cellular complexes that break down proteins. They are being studied in the treatment of cancer; and three are approved for use in treating multiple myeloma.
Multiple mechanisms are likely to be involved, but proteasome inhibition may prevent degradation of pro-apoptotic factors such as the p53 protein, permitting activation of programmed cell death in neoplastic cells dependent upon suppression of pro-apoptotic pathways. For example, bortezomib causes a rapid and dramatic change in the levels of intracellular peptides.
- 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 (salinosporamide A) has started clinical trials for multiple myeloma.
- Oprozomib (ONX-0912), delanzomib (CEP-18770) 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.
- Bortezomib (Velcade) 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 (Kyprolis) 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 (Ninlaro) 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 
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Skeletal muscle proteolysis is increased in catabolic states such as fasting, immobilization, aging, and disease . HMB has been shown to decrease skeletal muscle protein degradation both in vitro[72,73] and in vivo. ... Indeed, HMB has been shown to decrease proteasome expression  and activity [72,78-80] during catabolic states, thus attenuating skeletal muscle protein degradation through the ubiquitin-proteasome pathway.
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HMB, a derivative of leucine, prevents muscle damage and increases muscle strength by reducing exercise-induced proteolysis in muscles and also helps in increasing lean body mass.
- Wilkinson DJ, Hossain T, Hill DS, Phillips BE, Crossland H, Williams J, Loughna P, Churchward-Venne TA, Breen L, Phillips SM, Etheridge T, Rathmacher JA, Smith K, Szewczyk NJ, Atherton PJ (June 2013). "Effects of leucine and its metabolite β-hydroxy-β-methylbutyrate on human skeletal muscle protein metabolism". J. Physiol. 591 (11): 2911–2923. doi:10.1113/jphysiol.2013.253203. PMC 3690694. PMID 23551944.
although orally supplied HMB produced no increase in plasma insulin, it caused a depression in MPB (−57%). Normally, postprandial decreases in MPB (of ∼50%) are attributed to the nitrogen-sparing effects of insulin since clamping insulin at post-absorptive concentrations (5 μU ml−1) while continuously infusing AAs (18 g h−1) did not suppress MPB (Greenhaff et al. 2008), which is why we chose not to measure MPB in the Leu group, due to an anticipated hyperinsulinaemia (Fig. 3C). Thus, HMB reduces MPB in a fashion similar to, but independent of, insulin. These findings are in-line with reports of the anti-catabolic effects of HMB suppressing MPB in pre-clinical models, via attenuating proteasomal-mediated proteolysis in response to LPS (Eley et al. 2008).
- Bonvini P, Zorzi E, Basso G, Rosolen A (2007). "Bortezomib-mediated 26S proteasome inhibition causes cell-cycle arrest and induces apoptosis in CD-30+ anaplastic large cell lymphoma". Leukemia. 21 (4): 838–42. doi:10.1038/sj.leu.2404528. PMID 17268529.
- "Press Announcements — FDA approves Kyprolis for some patients with multiple myeloma". U.S. Food and Drug Administration. July 20, 2012. Retrieved 24 April 2016.
- "Press Announcements — FDA approves Ninlaro, new oral medication to treat multiple myeloma". U.S. Food and Drug Administration. Retrieved 24 April 2016.