BC-1471 is a STAMBP deubiquitinase inhibitor with an IC50 of 0.33μM [1]. BC-1471 can inhibit the cleavage of di-ubiquitin and block the ability of recombinant STAMBP to deubiquitinate the physiologically relevant substrate Ub-NALP7 [2]. BC-1471 has been widely used for regulating deubiquitination processes, and has also been employed as a model compound to screen specific STAMBP inhibitors[3].
In vitro, BC-1471 pretreatment for 2h at 10μM resulted in a significant decrease in the endogenous NALP7 abundance in THP-1 cells[4]. BC-1471 pretreatment (10μM) for 2 hours inhibited the release of IL-1β in human peripheral blood mononuclear cells (PBMCs) exposed to lipopolysaccharide (LPS)[4].
References:
[1] Pan X, Wu S, Wei W, et al. Structural and functional basis of JAMM deubiquitinating enzymes in disease[J]. Biomolecules, 2022, 12(7): 910.
[2] Schauer N J, Magin R S, Liu X, et al. Advances in discovering deubiquitinating enzyme (DUB) inhibitors[J]. Journal of medicinal chemistry, 2019, 63(6): 2731-2750.
[3] Wu H Q, Baker D, Ovaa H. Small molecules that target the ubiquitin system[J]. Biochemical Society Transactions, 2020, 48(2): 479-497.
[4] Bednash J S, Weathington N, Londino J, et al. Targeting the deubiquitinase STAMBP inhibits NALP7 inflammasome activity[J]. Nature communications, 2017, 8(1): 15203.
BC-1471是一种STAMBP去泛素化酶抑制剂，IC50值为0.33µM[1]。BC-1471 能够抑制二聚化的泛素的裂解过程，并阻断重组的STAMBP对生理相关底物 Ub-NALP7 的去泛素化能力[2]。BC-1471已被广泛用于调控去泛素化过程，并作为模型化合物用于筛选特异性STAMBP抑制剂[3]。
在体外，使用10µM的BC-1471预处理THP-1细胞2小时，导致内源性NALP7丰度显著下降[4]。用10µM的BC-1471预处理2小时，抑制了暴露于脂多糖（LPS）的人外周血单核细胞（PBMCs）中IL-1β的释放[4]。