inhibitor of Ubiquitin-Activating Enzyme (E1)
CAS：418805-02-4
分子式：C17H13N3O7
分子量：371.3
纯度：98%
存储：Store at -20°C

Background:

Ubiquitylation is catalyzed by the sequential action of ubiquitinactivating enzyme (E1), a ubiquitin-conjugating enzyme (E2) and a ubiquitin protein ligase (E3). Ubiquitylation is essential to numerous cellular and developmental processes, including protein quality control, growth, apoptosis, antigen presentation, DNA repair, and signal transduction. PYR-41, 4[4-(5-nitro-furan-2-ylmethylene)-3,5-dioxo-pyrazolidin-1-yl]-benzoic acid ethyl ester, is a selective inhibitor of Ubiquitin-Activating Enzyme (E1).

In vitro: In addition to blocking ubiquitylation, PYR-41 was found to increase total sumoylation in cells. PYR-41 could attenuate cytokine-mediated nuclear factor-KBactivation. This correlated with inhibition of nonproteasomal ubiquitylation of TRAF6, which is important to IKBkinase activation. PYR-41 also prevented the downstream ubiquitylation and proteasomal degradation of IKBA. Moreover, PYR-41 has demonstrated effective UAE E1 inhibition as well as some off-target inhibition of the other ubiquitin regulatory enzymes and signal-transducing proteins, suggesting it is a nonspecific inhibitor [1].

In vivo: No animal in vivo data have been published so far.

Clinical trial: Up to now, PYR-41 is still in the preclinical development stage.

Reference:
[1] Yang Y1 Kitagaki J, Dai RM, Tsai YC, Lorick KL, Ludwig RL, Pierre SA, Jensen JP, Davydov IV, Oberoi P, Li CC, Kenten JH, Beutler JA, Vousden KH, Weissman AM.  Inhibitors of ubiquitin-activating enzyme (E1), a new class of potential cancer therapeutics. Cancer Res. 2007 Oct 1;67(19):9472-81.