Nicotinamide phosphoribosyltransferase (Nampt) converts nicotinamide into nicotinamide mononucleotide (NMN), which is subsequently converted to NAD+ by NMN adenyltransferase. Cancer cells commonly have an unusually high rate of NAD+ turnover, suggesting that inhibition of Nampt might selectively target cancer cells. STF-118804 is a small molecule inhibitor of Nampt (IC50s = 3-6 nM) that prevents NAD+ synthesis from nicotinamide. It inhibits the viability of multiple B-cell acute lymphoblastic leukemia (B-ALL) cell lines with nanomolar potency and induces apoptosis in MV4-11 cells. At 50 mg/kg for 20 days, STF-118804 has been shown to improve survival in an orthotopic xenotransplant model of high-risk ALL in mice. It has also been shown to target leukemia stem cells.
