Nicotinamide phosphoribosyltransferase (NAMPT) catalyzes the condensation of nicotinamide with 5-phosphoribosyl-1-pyrophosphate to yield nicotinamide mononucleotide, an intermediate step in the biosynthesis of nicotinamide adenine dinucleotide (NAD⁺). FK-866 is a highly specific non-competitive inhibitor of NAMPT (K_i = 0.4 nM), causing gradual NAD⁺ depletion.¹ In Hep-G₂ human liver carcinoma cells, NAD⁺ depletion by FK-866 directs delayed cell death by apoptosis (IC₅₀ = ~1 nM).¹ In normal human smooth muscle cells, FK-866 causes premature senescence, an effect that may be linked to decreased activity of the NAD⁺-dependent enzyme SIRT1.² Also, FK-866 induces autophagy in SH-SY5Y neuroblastoma cells, as indicated by the formation of LC3-positive vesicles.³

1 Hasmann, M., Schemainda, I. FK866, a highly specific noncompetitive inhibitor of nicotinamide phosphoribosyltransferase, represents a novel mechanism for induction of tumor cell apoptosis. Cancer Res 63 7436-7442 (2003).

2 van der Veer, E., Ho, C., O'Neil, C., et al. Extension of human cell lifespan by nicotinamide phosphoribosyltransferase. J Biol Chem 282(15) 10841-10845 (2007).

3 Billington, R.A., Genazzani, A.A., Travelli, C., et al. NAD depletion by FK866 induces autophagy. Autophagy 4(3) 385-387 (2008).

Hasmann, M., Schemainda, I. FK866, a highly specific noncompetitive inhibitor of nicotinamide phosphoribosyltransferase, represents a novel mechanism for induction of tumor cell apoptosis. Cancer Res 63 7436-7442 (2003).

Billington, R.A., Genazzani, A.A., Travelli, C., et al. NAD depletion by FK866 induces autophagy. Autophagy 4(3) 385-387 (2008).

van der Veer, E., Ho, C., O'Neil, C., et al. Extension of human cell lifespan by nicotinamide phosphoribosyltransferase. J Biol Chem 282(15) 10841-10845 (2007).