Tanzisertib

Tanzisertib (CC-930) is a potent inhibitor of JNK1/2/3 with IC50s of 61/7/6 nM, respectively, with potential antifibrotic activity.Tanzisertib (CC-930) inhibits the formation of phospho-cJun in human PBMC stimulated by phorbol-12-myristate-13-acetate and phytohemeagglutinin (IC50=1 μM) and it blocks the JNK pathway that is activated by pro-fibrotic cytokines in systemic sclerosis. Tanzisertib (CC-930) (1-2 μM) substantially reduces hepatocyte apoptosis and necrosis, abrogates apoptosis and necrosis in FC-loaded WT hepatocytes.Tanzisertib (CC-930) (10 and 30 mg/kg, p.o.) inhibits the production of TNFa by 23% and 77% in the acute rat LPS-induced TNFa production PK-PD model. Tanzisertib (CC-930) (150 mg/kg) prevents the development of fibrosis in different models. However, it can also induce the regression of pre-existing fibrosis. (In Vitro) :Tanzisertib (CC-930) inhibits the formation of phospho-cJun in human PBMC stimulated by phorbol-12-myristate-13-acetate and phytohemeagglutinin (IC50=1 μM) . Tanzisertib (CC-930) (1-2 μM) substantially reduces hepatocyte apoptosis and necrosis, abrogates apoptosis and necrosis in FC-loaded WT hepatocytes. Tanzisertib (CC-930) blocks the JNK pathway that is activated by pro-fibrotic cytokines in systemic sclerosis. (In Vivo) :Tanzisertib (CC-930) (10 and 30 mg/kg, p.o.) inhibits the production of TNFa by 23% and 77% in the acute rat LPS-induced TNFa production PK-PD model. Tanzisertib (CC-930) (150 mg/kg) prevents the development of fibrosis in different models, but can also induce the regression of pre-existing fibrosis.