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Nifuroxazide


ACCESSION NB: (CID 5337997)


DESCRIPTION:
Nifuroxazide (INN) is an oral nitrofuran antibiotic, patented since 1966 and used to treat colitis and diarrhea in humans and non-humans. In 1997, in an Ivory Coast promotional leaflet, SmithKline Beecham claimed that nifuroxazide (under the brand name "Ambatrol") is an anti-dehydration treatment, "neutralise[s] microbacterials" in diarrhoea, and has "a spectrum which covers most enteropathogenic microbacterials, Shigella, Escherichia Coli, Salmonella, Staphylococci, Klebsiella, Yersinia".

PHARMACODYNAMICS:
Nifuroxazide inhibits the constitutive phosphorylation of STAT3 in multiple myeloma (MM) cells by reducing Jak kinase autophosphorylation, and leads to down-regulation of the STAT3 target gene Mcl-1. Nifuroxazide causes a decrease in viability of primary myeloma cells and myeloma cell lines containing STAT3 activation, but not normal peripheral blood mononuclear cells. Although bone marrow stromal cells provide survival signals to myeloma cells, nifuroxazide can overcome this survival advantage. Reflecting the interaction of STAT3 with other cellular pathways, nifuroxazide shows enhanced cytotoxicity when combined with either the histone deacetylase inhibitor depsipeptide or the MEK inhibitor UO126. Therefore, using a mechanistic-based screen, we identified the clinically relevant drug nifuroxazide as a potent inhibitor of STAT signaling that shows cytotoxicity against myeloma cells that depend on STAT3 for survival.