4H-Thiopyran-4-one,tetrahydro-3,5-bis[(4-nitrophenyl)methylene]-1,1-dioxide

Description

Ubiquitin isopeptidase inhibitor I induces caspase activation and apoptosis (IC₅₀ = ~1.7 μM) through a Bcl-2-dependent and apoptosome-independent mitochondrial pathway that selectively inhibits ubiquitin isopeptidase activity (IC₅₀ = ~30 μM). It has also been shown to induce necrosis in apoptosis-resistant DKO cells.

Uses

Ubiquitin Isopeptidase Inhibitor I, G5 is a cell-permeable cross-conjugated unsaturated dienone compound.

in vitro

ubiquitin isopeptidase inhibitor i targeted the ubiquitinproteasome system via inhibiting the ubiquitin isopeptidases. ubiquitin isopeptidase inhibitor i could induce a rather unique apoptotic pathway, including a bcl-2-dependent but apoptosome-independent mitochondrial pathway with upregulation of the bh3-only protein noxa, stabilization of the inhibitor of apoptosis antagonist smac, but also the involvement of the death receptor pathway. moreover, the treatment of ubiquitin isopeptidase inhibitor i to cell extracts obtained from e1a cells did not inhibit the proteolytic activity of the proteasome, whereas mg-132 potently inhibited the cleavage of the llvy-amc substrate. in addition, noxa induction by ubiquitin isopeptidase inhibitor i could be inhibited by the specific rnai oligos efficiently. when apoptosis was scored, it was found that down-regulation of noxa was able to inhibit but did not suppress apoptosis and caspase activation in response to ubiquitin isopeptidase inhibitor i treatment [1].

IC 50

~30 μm

storage

Store at -20°C

References

[1] e. aleo, c. j. henderson, a. fontanini, et al. identification of new compounds that trigger apoptosome-independent caspase activation and apoptosis. cancer research 66(18), 9235-9244 (2006).