Itacitinib

Itacitinib (INCB039110) is an orally active selective inhibitor of JAK1 with an IC₅₀ value of 2 nM for human JAK1. Itacitinib inhibits IFN-γ-mediated phosphorylation of STAT1 and downstream pro-inflammatory signaling pathways. Itacitinib reduces the frequency and number of splenic neutrophils in mouse models, downregulates the levels of pro-inflammatory cytokines and chemokines, and inhibits pro-inflammatory gene expression pathways. Itacitinib improves survival rate and clinical scores in mouse models of hemophagocytic lymphohistiocytosis (HLH), and also suppresses metastasis in NSCLC models with high Rab1A expression. Itacitinib can be used for research on hemophagocytic lymphohistiocytosis and non-small cell lung cancer^[1][2][3][4]. IC50 & Target:JAK1^[1] In Vitro:Itacitinib adipate (50-2500 nM; 1 h pretreatment) dose-dependently inhibits IFN-γ-induced STAT1 phosphorylation in bone marrow-derived macrophages, with significant suppression observed at 2500, 500, and 50 nM concentrations^[1].
Itacitinib (INCB039110) is a potent and selective JAK1 inhibitor with an IC₅₀ value of 2 nM for human JAK1. Its selectivity for JAK1 is more than 20 times that for JAK2, and its selectivity for JAK3 and TYK2 is more than 100 times^[4]. In Vivo:Itacitinib adipate (120 mg/kg; p.o.; twice daily; for 5 or 6 consecutive days) significantly improves survival rate and clinical scores in mouse models of secondary HLH, while reducing tissue neutrophilia levels and the levels of multiple proinflammatory cytokines^[1].
Itacitinib adipate (120 mg/kg; p.o.; twice daily; for 30 consecutive days) is well tolerated in untreated wild-type mice and effectively inhibits IFN-γ-induced STAT1 phosphorylation in vivo^[1].
Itacitinib adipate (120 mg/kg; p.o.; twice daily; for 5 or 26 consecutive days) partially improves survival rate and clinical scores in a primary HLH mouse model, and exerts only mild effects on disease-related immune parameters and transcriptional profiles^[1].
Itacitinib adipate (25 mg/kg; intraperitoneal injection; administration schedule consists of 9 cycles, with 5 consecutive days of dosing followed by 2 days of withdrawal per cycle, lasting for 2 months) significantly inhibits the metastasis of non-small cell lung cancer with high Rab1A expression in the xenograft model derived from the A549-Rab1A-OE cell line, reduces bioluminescence flux and the number of metastatic organs; it also significantly reduces the number of metastatic organs in the non-small cell lung cancer xenograft model derived from the H358 cell line^[2].