Details of the Drug Therapeutic Target (DTT)

General Information of Drug Therapeutic Target (DTT) (ID: TTD1WIG)

DTT Name	Nicotinamide phosphoribosyltransferase (NAMPT)
Synonyms	Visfatin; PreBcell colonyenhancing factor 1; PreB cellenhancing factor; Pre-B-cell colony-enhancing factor 1; Pre-B cell-enhancing factor; PBEF1; PBEF; Nampt; NAmPRTase
Gene Name	NAMPT
DTT Type	Clinical trial target	[1]
BioChemical Class	Glycosyltransferases
UniProt ID	NAMPT_HUMAN
TTD ID	T54582
3D Structure	Download 2D Sequence (FASTA) Download 3D Structure (PDB) Download
EC Number	EC 2.4.2.12
Sequence	MNPAAEAEFNILLATDSYKVTHYKQYPPNTSKVYSYFECREKKTENSKLRKVKYEETVFY GLQYILNKYLKGKVVTKEKIQEAKDVYKEHFQDDVFNEKGWNYILEKYDGHLPIEIKAVP EGFVIPRGNVLFTVENTDPECYWLTNWIETILVQSWYPITVATNSREQKKILAKYLLETS GNLDGLEYKLHDFGYRGVSSQETAGIGASAHLVNFKGTDTVAGLALIKKYYGTKDPVPGY SVPAAEHSTITAWGKDHEKDAFEHIVTQFSSVPVSVVSDSYDIYNACEKIWGEDLRHLIV SRSTQAPLIIRPDSGNPLDTVLKVLEILGKKFPVTENSKGYKLLPPYLRVIQGDGVDINT LQEIVEGMKQKMWSIENIAFGSGGGLLQKLTRDLLNCSFKCSYVVTNGLGINVFKDPVAD PNKRSKKGRLSLHRTPAGNFVTLEEGKGDLEEYGQDLLHTVFKNGKVTKSYSFDEIRKNA QLNIELEAAHH
Function	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 of clock target gene expression by releasing the core clock component: CLOCK-ARNTL/BMAL1 heterodimer from NAD-dependent SIRT1-mediated suppression. Catalyzes the condensation of nicotinamide with 5-phosphoribosyl-1-pyrophosphate to yield nicotinamide mononucleotide, an intermediate in the biosynthesis of NAD.
KEGG Pathway	Nicotinate and nicotinamide metabolism (hsa00760 ) Metabolic pathways (hsa01100 )
Reactome Pathway	BMAL1 (R-HSA-1368108 )

Molecular Interaction Atlas (MIA) of This DTT

Molecular Interaction Atlas (MIA)

MIA Detail

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4 Clinical Trial Drug(s) Targeting This DTT

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
Daporinad	DMCU74R	leukaemia	2A60-2B33	Phase 2	[1]
CHS-828	DMTV4L7	Solid tumour/cancer	2A00-2F9Z	Phase 1/2	[1]
GMX1777	DMIFSN2	Solid tumour/cancer	2A00-2F9Z	Phase 1	[2]
OT-82	DMI24RF	Lymphoma	2A80-2A86	Phase 1	[3]
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Molecular Expression Atlas (MEA) of This DTT

Molecular Expression Atlas (MEA)

MEA Detail

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Disease Name	ICD 11	Studied Tissue	p-value	Fold-Change	Z-score
Acute myelocytic leukaemia	2C82	Bone marrow	3.06E-08	-0.63	-0.59
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References

1	Anticancer agent CHS-828 inhibits cellular synthesis of NAD. Biochem Biophys Res Commun. 2008 Mar 21;367(4):799-804.
2	The small molecule GMX1778 is a potent inhibitor of NAD+ biosynthesis: strategy for enhanced therapy in nicotinic acid phosphoribosyltransferase 1-... Mol Cell Biol. 2009 Nov;29(21):5872-88.
3	OT-82, a novel anticancer drug candidate that targets the strong dependence of hematological malignancies on NAD biosynthesis. Leukemia. 2020 Jul;34(7):1828-1839.