IKKβ-IN-1

IKKβ-IN-1 is a potent and orally active IkappaB (IKK-β) inhibitor with IC50 of 0.20 μM. IKKβ-IN-1 can reduce PGE2 and TNF-α production in mouse macrophage cells. IKKβ-IN-1 has the ability to protect mice against septic shock induced mortality[1].

Signaling Pathways >> NF-κB >> IKK

Research Areas >> Inflammation/Immunology

IKK-β:0.2 (IC50)

IKKβ-IN-1 (compound 7a) (0.1, 1 and 10 μM; 24 hours) does not show significant cytotoxicity at the tested three concentrations[1]. IKKβ-IN-1 (0.1, 1 and 10 μM; 1 hours) significantly reduces PGE2 production even at the low 0.1 μM concentration, and IC50 is 9.83 μM[1]. IKKβ-IN-1 (0.1, 1 and 10 μM; 1 hours) elicits 44% reduction of TNF-α production at 10 μM concentration, and IC50 is 6.27 μM[1]. Cell Viability Assay Cell Line: RAW 264.7 macrophage cells[1] Concentration: 0.1, 1 and 10 μM Incubation Time: 24 hours Result: Did not show significant cytotoxicity at the tested three concentrations.

IKKβ-IN-1 (5 or 50 mg/kg; PO, single) exhibits an efficient protection of LPS-induced production of the inflammatory mediators at both of the two administered doses[1]. Animal Model: C57BL/6 male mice (6 or 10 weeks; LPS-induced production of the inflammatory mediators)[1] Dosage: 5 or 50 mg/kg Administration: PO, single (1 hour before LPS injection; survival was monitored for 36 hours) Result: Exhibited an efficient protection of LPS-induced production of the inflammatory mediators at both of the two administered doses.

[1]. Elkamhawy A, Kim NY, Hassan AHE, et al. Thiazolidine-2,4-dione-based irreversible allosteric IKK-β kinase inhibitors: Optimization into in vivo active anti-inflammatory agents. Eur J Med Chem. 2020;188:111955.