VIP(pr)-619 is a broad-range DUB inhibitor with potential for further development as a chemotherapeutic agent in cancer therapy.
in vitro: VIP(pr)-619 induces HCT116 cell death with EC50 values of 6.3 μM [1]. The general deubiquitylase (DUB) inhibitor, VIP(pr)-619 attenuated KCa3.1 degradation, indicative of deubiquitylation being required for lysosomal delivery [2]. Proteasome inhibition by MG-132 and deubiquitinase inhibition by VIP(pr)-619 induces significant changes to the ubiquitin landscape, but that not all ubiquitination sites regulated by MG-132 and VIP(pr)-619 are likely substrates for the ubiquitin-proteasome system [3]. Cells were incubated with VIP(pr)-619, a broad-range, reversible inhibitor of ubiquitin isopeptidases. Incubation with VIP(pr)-619 led to morphological changes, the upregulation of heat shock proteins (HSP), including HSP70 and αB-crystallin, and