The Anti-inflammatory Effect of Selonsertib (GS-4997), an ASK1 Inhibitor, on LPS-Stimulated THP-1 Cells

Abstract

Selonsertib (GS-4997), a serine/threonine kinase inhibitor, targets apoptosis signal-regulating kinase 1 (ASK1) and is now in a phase III clinical trial for the treatment of non-alcoholic steatohepatitis (NASH). Inflammation is a defense against an effect that can damage the tissue or organ itself. Cytokines are the agents that play a key role in acute inflammation and one of the most important cytokine proteins, IL-1β. In this study, we investigated whether selonsertib and diclofenac sodium (positive control) could inhibit IL-1β caused by two different LPS (Salmonella enterica serotype enteritidis and Escherichia coli O111:B4) stimulated on THP-1 cell line. As a result of the WST-1 assay, the inhibitory concentration of diclofenac sodium at doses of IC50 of 32.5 μM/mL and selonsertib was calculated to be 120 μM/mL. The immunological responses of diclofenac sodium and selonsertib (IL-1β) in different LPS-stimulated THP-1 cells were assessed cytometrically: diclofenac sodium and Selonsertib were found to be effective in stimulation from E. coli. The results showed that selonsertib had a significantly anti-inflammatory effect like diclofenac sodium.