Vialinin A is a potent inhibitor of ubiquitin-specific peptidases with IC50 values of 1.5, 5.9 and 22.3 μM for ubiquitin-specific peptidase 4 (USP4), USP5/isopeptidase T (IsoT) and UCH-L1 deubiquitinating enzyme (DUB), respectively [1].
Ubiquitin-specific peptidases (USPs) are a series of proteases that deubiquitinate target proteins. The dynamic modification of a protein with ubiquitin can modify its function, localization and fate in the cell. Ubiquitin hydrolase plays an important role in immunology and infection [2].
In RBL-2H3 cells, vialinin A inhibited TNF-ɑ production and release and inhibited USP5 enzymatic activity. In USP5 siRNA-knockdown RBL-2H3 cells, vialinin A inhibited TNF-ɑ production and release in a dose dependent way. Also, the mRNA expression of TNF-ɑ was decreased significantly [2]. In RBL-2H3 cells, Vialinin A inhibited TNF-ɑ production with IC50 value of 0.09 nM. Also, it inhibited the release of interleukin 4, β-hexosaminidase and monocyte chemotactic protein 1, which suggested Vialinin A had anti-allergic activities [3].
References:
[1]. Okada K, Ye YQ, Taniguchi K, et al. Vialinin A is a ubiquitin-specific peptidase inhibitor. Bioorg Med Chem Lett, 2013, 23(15): 4328-4331.
[2]. Yoshioka Y, Ye YQ, Okada K, et al. Ubiquitin-specific peptidase 5, a target molecule of vialinin A, is a key molecule of TNF-α production in RBL-2H3 cells. PLoS One, 2013, 8(12): e80931.
[3]. Onose J, Xie C, Ye YQ, et al. Vialinin A, a novel potent inhibitor of TNF-alpha production from RBL-2H3 cells. Biol Pharm Bull, 2008, 31(5): 831-833.