IC50: ~30 μM

Ubiquitin Isopeptidase Inhibitor I is a ubiquitin isopeptidase inhibitor.

Conjugation or deconjugation of ubiquitin or ubiquitin-like proteins to or from cellular proteins is a multifaceted and universal ways of regulating cellular physiology, controlling the lifetime, localization, and activity of various key proteins.

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].

In vivo: So far, there is no animal in vivo data reported.

Clinical trial: Up to now, Ubiquitin Isopeptidase Inhibitor I is still in the preclinical development stage.