FK-866 is a selective inhibitor of the nicotinamide pathway dependent NAD+ synthesis, causing NAD+ depletion. Highly specific, non-competitive inhibitor of nicotinamide phosphoribosyltransferase (NAMPT/NAPRT) for both the substrate complex and the free enzyme (Ki=0.4 nM and Ki?=0.3 nM, respectively). NAD+ depletion by FK-866 directs delayed cell death by apoptosis in Hep-G2 human liver carcinoma cells (IC50=~1 nM). Causes premature senescence in normal human smooth muscle cells, an effect that may be linked to decreased activity of the NAD+-dependent enzyme SIRT1.