Target General Infomation
Target ID
T54582
Former ID
TTDI02132
Target Name
Nicotinamide phosphoribosyltransferase
Gene Name
NAMPT
Synonyms
NAmPRTase; Nampt; PreB cellenhancing factor; PreBcell colonyenhancing factor 1; Visfatin; NAMPT
Target Type
Clinical Trial
Disease Leukemia [ICD9: 208.9; ICD10: C90-C95]
Solid tumours [ICD9: 140-199, 210-229; ICD10: C00-D48]
Function
Catalyzes the condensation ofnicotinamide with 5- phosphoribosyl-1-pyrophosphate to yield nicotinamide mononucleotide, an intermediate in the biosynthesis of NAD. It is the rate limiting component in the mammalian NAD biosynthesis pathway. The secreted form behaves both as a cytokine with immunomodulating properties and an adipokine with anti-diabetic properties, it has no enzymatic activity, partly because of lack of activation by ATP, which has a low level in extracellular space and plasma. Plays a role in the modulation of circadian clock function. NAMPT-dependent oscillatory production of NAD regulates oscillation ofclock target gene expression by releasing the core clock component: CLOCK-ARNTL/BMAL1 heterodimer from NAD-dependent SIRT1-mediated suppression (By similarity).
BioChemical Class
Pentosyltransferase
UniProt ID
EC Number
EC 2.4.2.12
Sequence
MNPAAEAEFNILLATDSYKVTHYKQYPPNTSKVYSYFECREKKTENSKLRKVKYEETVFY
GLQYILNKYLKGKVVTKEKIQEAKDVYKEHFQDDVFNEKGWNYILEKYDGHLPIEIKAVP
EGFVIPRGNVLFTVENTDPECYWLTNWIETILVQSWYPITVATNSREQKKILAKYLLETS
GNLDGLEYKLHDFGYRGVSSQETAGIGASAHLVNFKGTDTVAGLALIKKYYGTKDPVPGY
SVPAAEHSTITAWGKDHEKDAFEHIVTQFSSVPVSVVSDSYDIYNACEKIWGEDLRHLIV
SRSTQAPLIIRPDSGNPLDTVLKVLEILGKKFPVTENSKGYKLLPPYLRVIQGDGVDINT
LQEIVEGMKQKMWSIENIAFGSGGGLLQKLTRDLLNCSFKCSYVVTNGLGINVFKDPVAD
PNKRSKKGRLSLHRTPAGNFVTLEEGKGDLEEYGQDLLHTVFKNGKVTKSYSFDEIRKNA
QLNIELEAAHH
Drugs and Mode of Action
Drug(s) Daporinad Drug Info Phase 2 Leukemia [529259], [542710]
CHS-828 Drug Info Phase 1/2 Solid tumours [529259]
GMX1777 Drug Info Phase 1 Solid tumours [530334]
Inhibitor CHS-828 Drug Info [529259], [532983]
Daporinad Drug Info [529259]
Modulator GMX1777 Drug Info [530334]
Target Expression Profile (TEP) and Drug Resistance Mutation (DRM)
TEP EXP Info
Pathways
BioCyc Pathway NAD salvage
KEGG Pathway Nicotinate and nicotinamide metabolism
Metabolic pathways
NetPath Pathway IL2 Signaling Pathway
IL1 Signaling Pathway
TCR Signaling Pathway
PathWhiz Pathway Nicotinate and Nicotinamide Metabolism
Reactome CLOCK,NPAS2 activates circadian gene expression
WikiPathways Adipogenesis
Metabolism of water-soluble vitamins and cofactors
Circadian Clock
References
Ref 529259Anticancer agent CHS-828 inhibits cellular synthesis of NAD. Biochem Biophys Res Commun. 2008 Mar 21;367(4):799-804.
Ref 530334Mol Cell Biol. 2009 Nov;29(21):5872-88. Epub 2009 Aug 24.The small molecule GMX1778 is a potent inhibitor of NAD+ biosynthesis: strategy for enhanced therapy in nicotinic acid phosphoribosyltransferase 1-deficient tumors.
Ref 542710(http://www.guidetopharmacology.org/) Nucleic Acids Res. 2015 Oct 12. pii: gkv1037. The IUPHAR/BPS Guide to PHARMACOLOGY in 2016: towards curated quantitative interactions between 1300 protein targets and 6000 ligands. (Ligand id: 7745).
Ref 529259Anticancer agent CHS-828 inhibits cellular synthesis of NAD. Biochem Biophys Res Commun. 2008 Mar 21;367(4):799-804.
Ref 530334Mol Cell Biol. 2009 Nov;29(21):5872-88. Epub 2009 Aug 24.The small molecule GMX1778 is a potent inhibitor of NAD+ biosynthesis: strategy for enhanced therapy in nicotinic acid phosphoribosyltransferase 1-deficient tumors.
Ref 532983Structural basis for resistance to diverse classes of NAMPT inhibitors. PLoS One. 2014 Oct 6;9(10):e109366.

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