HOIPIN-8

• CAT Number: I028846
• Molecular Formula: C23H15F2N4NaO3
• Molecular Weight: 456.38
• Purity: ≥95%
• Synonyms: sodium;2-[(E)-3-[2,6-difluoro-4-(1H-pyrazol-4-yl)phenyl]-3-oxoprop-1-enyl]-4-(1-methylpyrazol-4-yl)benzoate
• InChI: InChI=1S/C23H16F2N4O3.Na/c1-29-12-17(11-28-29)13-2-4-18(23(31)32)14(6-13)3-5-21(30)22-19(24)7-15(8-20(22)25)16-9-26-27-10-16;/h2-12H,1H3,(H,26,27)(H,31,32);/q;+1/p-1/b5-3+
• InChIKey: DLJPWYFLGYVMKV-WGCWOXMQSA-M
• SMILES: CN1C=C(C=N1)C2=CC(=C(C=C2)C(=O)[O-])C=CC(=O)C3=C(C=C(C=C3F)C4=CNN=C4)F.[Na+]

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].

Reference

[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.
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