HMB-Val-Ser-Leu-VE is an irreversible, cell-permeable, potent and specific inhibitor of the trypsin-like activity of the 20S proteasome with IC50 value of 33 nM [1].
The 20S proteasome is a 700 kDa, cylinder-shaped protease with multiple catalytic centers within the ubiquitin-proteasome pathway and plays an important role in the selective degradation of intracellular proteins. Proteasomes remove abnormal proteins and play an important role in cell-cycle progression and apoptosis [1][2].
HMB-Val-Ser-Leu-VE is a tripeptide-based compound bearing a C-terminal vinyl ester that acts as a potent and selective inhibitor of the trypsin-like activity of the 20S proteasome with IC50 value of 33 nM [1]. In two colon-carcinoma cell lines (COO115, HCT116), HMB-Val-Ser-Leu-VE was nontoxic and did not affect cell proliferation. In HLA-A2 positive lymphoblastoid cells, HMB-Val-Ser-Leu-VE caused a dose-dependent increase of CLG-specific killing, suggesting that HMB-Val-Ser-Leu-VE favored the generation and presentation of immunogenic peptides presented by MHC class I molecules [1].
References:
[1]. Marastoni M, Baldisserotto A, Cellini S, et al. Peptidyl vinyl ester derivatives: new class of selective inhibitors of proteasome trypsin-like activity. J Med Chem. 2005 Jul 28;48(15):5038-42.
[2]. DeMartino GN, Slaughter CA. The proteasome, a novel protease regulated by multiple mechanisms.