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 (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. Induces autophagy in SH-SY5Y neuroblastoma cells, as indicated by the formation of LC3-positive vesicles.
Product Details
| Alternative Name: | K 22.175, N-[4-(1-benzoyl-4-piperidinyl)butyl]-3-(3-pyridinyl)-2E-propenamide |
| |
| Formula: | C24H29N3O2 |
| |
| MW: | 391.5 |
| |
| Source: | Synthetic. |
| |
| CAS: | 658084-64-1 |
| |
| Purity: | ≥98% (NMR) |
| |
| Appearance: | White to yellow solid. |
| |
| Solubility: | Soluble in 100% ethanol, dimethyl formamide (40mg/ml) or DMSO (25mg/ml); sparingly soluble in aqueous buffers. |
| |
| Shipping: | Blue Ice |
| |
| Long Term Storage: | -20°C |
| |
| Handling: | Very hygroscopic Packaged under inert gas. Keep under inert gas. |
| |
| Scientific Background: | 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. |
| |
| Regulatory Status: | RUO - Research Use Only |
| |
Please mouse over
Product Literature References
Effects of Chronic NAD Supplementation on Energy Metabolism and Diurnal Rhythm in Obese Mice: E. Roh, et al.; Obesity
26, 1148 (2018),
Abstract;
Targeting of nicotinamide phosphoribosyltransferase enzymatic activity ameliorates lung damage induced by ischemia/reperfusion in rats: G.C. Wu, et al.; Respir. Res.
18, 71 (2017),
Application(s): Lung damage on rat and human alveiolar epithelial cells,
Abstract;
Full Text
A novel potent nicotinamide phosphoribosyltransferase inhibitor synthesized via click chemistry: G. Colombano, et al.; J. Med. Chem.
53, 616 (2010),
Abstract;
Inhibition of lactate dehydrogenase A induces oxidative stress and inhibits tumor progression: A. Lee, et al.; PNAS
107, 2037 (2010),
Abstract;
Catastrophic NAD+ depletion in activated T lymphocytes through Nampt inhibition reduces demyelination and disability in EAE: S. Bruzzone, et al.; PLoS One
4, e7897 (2009),
Abstract;
Circadian control of the NAD+ salvage pathway by CLOCK-SIRT1: Y. Nakahata, et al.; Science
324, 654 (2009),
Abstract;
Detection and pharmacological modulation of nicotinamide mononucleotide (NMN) in vitro and in vivo: L. Formentini, et al.; Biochem. Pharmacol.
77, 1612 (2009),
Abstract;
NAD depletion by FK866 induces autophagy: R.A. Billington, et al.; Autophagy
4, 385 (2008),
Abstract;
Extension of human cell lifespan by nicotinamide phosphoribosyltransferase: E. van der Veer, et al.; J. Biol. Chem.
282, 10841 (2007),
Abstract;
Chemopotentiating effects of a novel NAD biosynthesis inhibitor, FK866, in combination with antineoplastic agents: A. Pogrebniak, et al.; Eur. J. Med. Res.
11, 313 (2006),
Abstract;
FK866, a highly specific noncompetitive inhibitor of nicotinamide phosphoribosyltransferase, represents a novel mechanism for induction of tumor cell apoptosis: M. Hasmann & I. Schemainda; Cancer Res.
63, 7436 (2003),
Abstract;
