Nifuroxazide (Diarlidan) is an orally available and cell-permeable nitrofuran-based antidiarrheal agent. It has the inhibitory effect against the activation of cellular STAT1/3/5 transcription.

Nifuroxazide does not affect the phosphorylation of Akt or MAPK. It inhibits the survival of myeloma cells by reducing the autophosphorylation of Jak kinases, thereby blocking the constitutive phosphorylation of STAT3, but has no effect on normal peripheral blood mononuclear cells. Nifuroxazide decreases the tyrosine phosphorylation of TYK2 and Jak, demonstrating selectivity towards TYK2 and Jak2 without impacting the tyrosine kinases of the EGF receptor or Src kinase. This effect is achieved through the reduction of Jak kinases' autophosphorylation, leading to the inhibition of constitutive phosphorylation of STAT3 in MM (multiple myeloma) cells and the downregulation of the STAT3 target gene, Mcl-1. Consequently, Nifuroxazide reduces the viability of primary myeloma cells and cell lines with activated STAT3 but does not affect normal peripheral blood mononuclear cells. It also blocks the survival signals provided by bone marrow stromal cells to myeloma cells. Compared to interactions with other cellular pathways, Nifuroxazide shows increased cytotoxicity when combined with the histone deacetylase inhibitor Trichostatin or the MEK inhibitor UO126, targeting STAT3.