(E)-N-[4-(1-BENZOYL-PIPERIDIN-4-YL)-BUTYL]-3-PYRIDIN-3-YL-ACRYLAMIDE

Описание

FK-866 is a highly specific non-competitive inhibitor of Nampt (K_i = 0.4 nM), causing gradual NAD⁺ depletion. In HepG2 human liver carcinoma cells, NAD⁺ depletion by FK-866 directs delayed cell death by apoptosis (IC₅₀ = ~1 nM). 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. Also, FK-866 induces autophagy in SH-SY5Y neuroblastoma cells, as indicated by the formation of LC3-positive vesicles.

Использование

FK866 hydrochloride hydrate has been used:

• to investigate its effects on intra-axonal NAD⁺ levels
• to induce NAD+ depletion
• to reduce the level of tumor necrosis factor-α (TNF-α), nicotinamide phosphoribosyltransferase (NAMPT) and interleukin-6 (IL-6) in the ischemic brain tissue

Общее описание

A cell-permeable pyridinylacrylamide compound that acts as a selective, allosteric NAPRT/NAMPT (nicotinamide phosphoribosyltransferase) inhibitor (K_i = 0.4 nM for the enzyme/substrate complex; K_i^′ = 0.3 nM for the free enzyme), while exhibiting no effect toward NPRT (nicotinic acid phosphoribosyltransferase) activity (82% inhibition of NAPRT activity at 10 nM vs no inhibition of NPRT activity at 1 μM in K-562 extract). FK866 treatment is shown to induce cell death by depleting NAD⁺ (Cat. Nos. 481911 & 481915) in HepG2 and NIH-3T3 cultures (by >95% after 24 h treatment of 10 nM FK866), likewise the addition of exogenous NAD⁺ is demonstrated to rescue NIH-3T3 and SH-SY5Y from FK866-induced NAD⁺-depletion and cell death.