FK-866

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 enzyme/substrate complex and the free enzyme (K_i=0.4 nM and K_i´=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. Induces autophagy in SH-SY5Y neuroblastoma cells, as indicated by the formation of LC3-positive vesicles.

NAMPT catalyzes the condensation of nicotinamide with 5-phosphoribosyl-1-pyrophosphate to yield nicotinamide mononucleotide, an intermediate in the biosynthesis of NAD⁺. It is the major rate limiting component in the mammalian NAD⁺ biosynthesis pathway.