HOIPIN-8

HOIPIN-8 is a potent inhibitor of linear ubiquitin chain assembly complex (LUBAC) with an IC50 of 11 nM. HOIPIN-8 is a HOIPIN-1 derivative with enhanced the potency by 255-fold in the petit-LUBAC inhibition, and 10-fold and 4-fold in the LUBAC- and TNF-α-mediated NF-κB activation, respectively than HOIPIN-1. HOIPIN-1 is a promising tool to explore the cellular functions of LUBAC[1].

HOIPIN-8 (0-100 μM; 72 hours) has little cell toxicity on A549 cells, and exhibits an IC50 value of 100 μM[1].HOIPIN-8 (0-10 μM; 24 hours) has an inhibitory effect over 10-fold enhancement over that of HOIPIN-1 on NF-κB activation, exhibits an IC50 value of 0.42?μM in HEK293T cells[1].HOIPIN-8 (0-30 μM; NF-κB luciferase reporter is transfected into cells for 18 hours; then with 10?ng/ml TNF-α for 6?h) exhibits a 4-fold enhancements of the potency than HOIPIN-1, the IC50 value is 11.9 μM. It also effectively reduces IL-1β-induced expression of NF-κB target genes, such as ICAM1 and IL-6 as compared to HOIPIN-1[1].

[1]. Ken Katsuya, et al. Small-molecule Inhibitors of Linear Ubiquitin Chain Assembly Complex (LUBAC), HOIPINs, Suppress NF-κB Signaling. Biochem Biophys Res Commun. 2019 Feb 12;509(3):700-706.