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FK-866

Nampt inhibitor
 
ALX-270-501-M001 1 mg 94.00 USD
 
ALX-270-501-M005 5 mg 145.00 USD
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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 Specification

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:Shipped on 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.
 
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Product Literature References

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;

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