NAMPT

Summary

NAMPT (nicotinamide phosphoribosyltransferase, HGNC:30092) is a protein-coding gene on chromosome 7q22.3, encoding Nicotinamide phosphoribosyltransferase (P43490). Catalyzes the condensation of nicotinamide with 5-phosphoribosyl-1-pyrophosphate to yield nicotinamide mononucleotide, an intermediate in the biosynthesis of NAD. It is a selective cancer dependency (DepMap: 33.6% of cell lines).

This gene encodes a protein that catalyzes the condensation of nicotinamide with 5-phosphoribosyl-1-pyrophosphate to yield nicotinamide mononucleotide, one step in the biosynthesis of nicotinamide adenine dinucleotide. The protein belongs to the nicotinic acid phosphoribosyltransferase (NAPRTase) family and is thought to be involved in many important biological processes, including metabolism, stress response and aging. This gene has a pseudogene on chromosome 10.

Source: NCBI Gene 10135 — RefSeq curated summary.

At a glance

• GWAS associations: 2
• Clinical variants (ClinVar): 39 total
• Druggable target: yes — 4 molecules with ChEMBL bioactivity
• Cancer dependency (DepMap): dependent in 33.6% of screened cell lines
• MANE Select transcript: NM_005746

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:30092
Approved symbol	NAMPT
Name	nicotinamide phosphoribosyltransferase
Location	7q22.3
Locus type	gene with protein product
Status	Approved
Aliases	PBEF
Ensembl gene	ENSG00000105835
Ensembl biotype	protein_coding
OMIM	608764
Entrez	10135

Gene structure

Transcript identifiers

Ensembl transcripts: 53 — 22 protein_coding, 14 retained_intron, 13 nonsense_mediated_decay, 4 protein_coding_CDS_not_defined

ENST00000222553, ENST00000354289, ENST00000393618, ENST00000417537, ENST00000424768, ENST00000441045, ENST00000463871, ENST00000467730, ENST00000484527, ENST00000486949, ENST00000489358, ENST00000489732, ENST00000491027, ENST00000679461, ENST00000679643, ENST00000679717, ENST00000679873, ENST00000679894, ENST00000679951, ENST00000680077, ENST00000680129, ENST00000680152, ENST00000680468, ENST00000680482, ENST00000680516, ENST00000680584, ENST00000680616, ENST00000680669, ENST00000680675, ENST00000680708, ENST00000680786, ENST00000680823, ENST00000680864, ENST00000680991, ENST00000681223, ENST00000681255, ENST00000681297, ENST00000681372, ENST00000681391, ENST00000681455, ENST00000681456, ENST00000681491, ENST00000681494, ENST00000681550, ENST00000681631, ENST00000681653, ENST00000681878, ENST00000681887, ENST00000681936, ENST00000901886, ENST00000901887, ENST00000921397, ENST00000968694

RefSeq mRNA: 1 — MANE Select: NM_005746 NM_005746

CCDS: CCDS5737

Canonical transcript exons

ENST00000222553 — 11 exons

Exon	Start	End
ENSE00000714587	106263392	106263617
ENSE00000714588	106261588	106261707
ENSE00000714590	106254364	106254504
ENSE00000714592	106253017	106253151
ENSE00000881741	106248298	106251193
ENSE00001516080	106284828	106284983
ENSE00003465913	106277023	106277179
ENSE00003517363	106269154	106269312
ENSE00003655156	106274946	106275049
ENSE00003666475	106268464	106268600
ENSE00003687091	106272530	106272658

Expression profiles

Bgee: expression breadth ubiquitous, 291 present calls, max score 99.42.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 211.0872 / max 19186.5621, expressed in 1824 samples.

FANTOM5 promoters (31 alternative TSS)

Promoter ID	TPM avg	Samples expressed
85541	102.1935	1789
85542	79.5813	1815
85543	12.5390	1752
85490	9.7423	868
85539	2.4761	1088
85548	0.7883	95
85549	0.7010	95
85537	0.3660	86
85496	0.2372	28
204636	0.2291	68

Top tissues by expression

294 total, by Bgee expression score (0-100, higher = more expressed):

Tissue	Anatomy ID	Expression score	Quality
blood	UBERON:0000178	99.42	gold quality
pericardium	UBERON:0002407	99.28	gold quality
mucosa of stomach	UBERON:0001199	99.02	gold quality
lower esophagus mucosa	UBERON:0035834	98.99	gold quality
right lung	UBERON:0002167	98.83	gold quality
vena cava	UBERON:0004087	98.79	gold quality
upper lobe of left lung	UBERON:0008952	98.76	gold quality
left uterine tube	UBERON:0001303	98.73	gold quality
upper lobe of lung	UBERON:0008948	98.69	gold quality
cauda epididymis	UBERON:0004360	98.63	gold quality
lower lobe of lung	UBERON:0008949	98.49	gold quality
gall bladder	UBERON:0002110	98.40	gold quality
adrenal tissue	UBERON:0018303	98.32	gold quality
monocyte	CL:0000576	98.24	gold quality
pharyngeal mucosa	UBERON:0000355	98.24	gold quality
esophagus mucosa	UBERON:0002469	98.24	gold quality
peritoneum	UBERON:0002358	98.17	gold quality
omental fat pad	UBERON:0010414	98.17	gold quality
nipple	UBERON:0002030	98.08	gold quality
mononuclear cell	CL:0000842	97.83	gold quality
leukocyte	CL:0000738	97.78	gold quality
adipose tissue of abdominal region	UBERON:0007808	97.74	gold quality
mucosa of paranasal sinus	UBERON:0005030	97.65	gold quality
minor salivary gland	UBERON:0001830	97.52	gold quality
periodontal ligament	UBERON:0008266	97.49	gold quality
heart right ventricle	UBERON:0002080	97.48	gold quality
vermiform appendix	UBERON:0001154	97.46	gold quality
islet of Langerhans	UBERON:0000006	97.39	gold quality
right lobe of liver	UBERON:0001114	97.28	gold quality
saphenous vein	UBERON:0007318	97.26	gold quality

Single-cell (SCXA)

Detected in 44 experiment(s), a significant marker in 38.

Experiment	Marker?	Max mean expression
E-MTAB-9221	yes	53125.90
E-MTAB-6678	yes	15051.71
E-GEOD-149689	yes	12152.16
E-GEOD-139324	yes	9179.68
E-HCAD-36	yes	9052.55
E-GEOD-150728	yes	8121.76
E-HCAD-15	yes	6745.67
E-GEOD-130148	yes	5553.65
E-HCAD-32	yes	4280.08
E-MTAB-10855	yes	4017.30
E-CURD-112	yes	3950.59
E-CURD-120	yes	3931.62
E-CURD-126	yes	3755.93
E-CURD-46	yes	3726.96
E-MTAB-9841	yes	3362.76

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): BMAL1, CLOCK, HIF1A, JUN, NEUROD1, NFKB1, NFKB, PPARA, PPARD, PPARG, PRKAA1, RELA, RORB

Functional genomics

DepMap (CRISPR cell-line fitness): dependent in 33.6% of screened cell lines.

Literature-anchored findings (GeneRIF, showing 40)

• PBEF1 is upregulated in neutrophils by IL-1beta and functions as a novel inhibitor of apoptosis in response to a variety of inflammatory stimuli. (PMID:15124023)
• These findings identify PBEF1 as a regulator of NAD+-dependent reactions in smooth muscle cells (SMCs), reactions that promote, among other potential processes, the acquisition of a mature SMC phenotype. (PMID:15947248)
• Although PBEF had no chemotaxic effects, it was antiapoptotic for both amniotic epithelial cells and fibroblasts and may protect these cells against apoptosis that is induced by chronic distension, labor, or infection. (PMID:16021090)
• visfatin plasma concentrations and visceral visfatin messenger RNA expression correlated with measures of obesity but not with visceral fat mass or waist-to-hip ratio (PMID:16186392)
• PBEF contributes to acute lung injury susceptibility (PMID:16188281)
• visfatin may play a role in the pathogenesis of type 2 diabetes mellitus (PMID:16234302)
• A true adipokine, but it is not regulated by thiazolidineidones and, thus unlikely to contribute to the insulin-sensitizing actions of these drugs. (PMID:16394088)
• increased macrophage population in obese human visceral white adipose tissue might be responsible for the enhanced production of chemokines as well as resistin and visfatin (PMID:16496121)
• Visfatin/pre-B-cell colony-enhancing factor appears to be preferentially produced by the visceral adipose tissue and has insulin mimetic actions (PMID:16531748)
• data suggest that genetic variation in the visfatin gene may have a minor effect on visceral and subcutaneous visfatin messenger RNA expression profiles but does not play a major role in the development of obesity or type 2 diabetes mellitus (PMID:16636125)
• These data show that an inflammatory stimulus in the fetal membranes inducing NF-kappaB and AP-1 would up-regulate PBEF as well as IL-8. (PMID:16701870)
• findings show that, in human obesity, plasma visfatin is reduced, whereas visfatin mRNA is differentially regulated in adipose tissue (PMID:16720654)
• Circulating visfatin concentrations are increased by hyperglycaemia. This effect is suppressed by exogenous hyperinsulinaemia or somatostatin infusion. (PMID:16736128)
• FK866 is bound in a tunnel at the interface of the NMPRTase dimer, and mutations in this binding site can abolish the inhibition by FK866, providing a starting point for the development of new anticancer agents. (PMID:16783377)
• Pre-B cell colony-enhancing factor (PBEF) is regulated via IL-6 trans-signaling and the IL-6-related cytokine OSM. PBEF is also actively expressed during arthritis. (PMID:16802343)
• results show that there are decreased concentrations of plasma visfatin in gestational diabetes mellitus subjects and this may indicate that visfatin plays a role in the pathogenesis of gestational diabetes mellitus (PMID:16814166)
• visfatin is a new hypoxia-inducible gene of which expression is stimulated through the interaction of HIF-1 with HRE sites in its promoter region. (PMID:16828081)
• visfatin has a local metabolic role in the recovery period following exercise. (PMID:16868228)
• The results indicate that hyperglycemia causes an increase in plasma visfatin levels and, as in people with diabetes mellitus type 2 but not with impaired glucose tolerance, this increase gets more prominent as the glucose intolerance worsens. (PMID:16956691)
• circulating visfatin is increased with progressive beta-cell deterioration. (PMID:17003355)
• A significant association was found between two SNPs of visfatin (rs9770242 and rs1319501), in perfect linkage disequilibrium, and fasting insulin levels (P = 0.002). (PMID:17003359)
• visfatin is highly expressed in lean, more insulin-sensitive subjects and is attenuated in subjects with high intramyocellular lipids, low insulin sensitivity, and high levels of inflammatory markers (PMID:17090638)
• potential link with pathogenesis of glucose resistance and type 2 diabetes (PMID:17177135)
• In patients with inflammatory bowel disease, plasma levels of visfatin are elevated and its mRNA expression is significantly increased in colonic tissue of Crohn’s and ulcerative colitis patients (PMID:17237424)
• Circulating levels of the cytokine visfatin/PBEF-1 are influenced by renal function, but are not associated with fat mass or surrogate markers of insulin resistance in patients with chronic kidney disease. (PMID:17261426)
• Visfatin is down-regulated by overfeeding (PMID:17284735)
• Nampt is a longevity protein that can add stress-resistant life to human smooth muscle cells by optimizing SIRT1-mediated p53 degradation (PMID:17307730)
• Serum visfatin concentration is significantly associated with parameters of iron metabolism, especially in subjects with altered glucose tolerance. (PMID:17327330)
• An increase in fasting visfatin, the levels of which correlate with both fasting and post-glucose-load insulin concentrations, accompanies worsening glucose tolerance in the third trimester of pregnancy. (PMID:17334748)
• Women with PCOS exhibit higher plasma visfatin levels than control subjects of similar body mass index. (PMID:17335820)
• the regulation of glucose uptake, proliferation, and type I collagen production by visfatin in human osteoblasts involves IR phosphorylation, the same signal-transduction pathway used by insulin (PMID:17340225)
• This review summarizes current knowledge of the various functions of PBEF/visfatin towards involvement in the pathophysiology of several diseases. (PMID:17392604)
• Taken together, these results demonstrate that visfatin promotes angiogenesis via activation of mitogen-activated protein kinase ERK-dependent pathway. (PMID:17408594)
• PBEF/NAMPT/visfatin level is an indicator of beneficial lipid profile in non-diabetic Caucasian subjects (PMID:17429683)
• Plasma visfatin levels are increased in overweight and obese subjects with metabolic syndrome. (PMID:17556870)
• Visfatin has a role in insulin resistance and markers of hyperandrogenism in lean PCOS patients (PMID:17582143)
• During fasting, increased Nampt provides protection against cell death and requires an intact mitochondrial NAD(+) salvage pathway as well as the mitochondrial NAD(+)-dependent deacetylases SIRT3 and SIRT4. (PMID:17889652)
• Circulating visfatin may be related with some proinflammatory condition even in a nondiabetic state (PMID:17904242)
• Rosuvastatin induced a significant decrease in plasma visfatin levels in patients with primary hyperlipidemia. (PMID:17931620)
• Visfatin, TNF-alpha, and IL-6 mRNA expressions are increased in peripheral mononuclear-monocytic cells from women with type 2 diabetes. (PMID:17952840)

Cross-species orthologs

7 orthologs

Organism	Symbol	Gene ID
danio_rerio	nampt1	ENSDARG00000030598
danio_rerio	nampt3.1	ENSDARG00000076694
danio_rerio	nampt3.2	ENSDARG00000078738
danio_rerio	nampt4.1	ENSDARG00000100321
danio_rerio	nampt4.2	ENSDARG00000112678
mus_musculus	Nampt	ENSMUSG00000020572
rattus_norvegicus	Nampt	ENSRNOG00000009754

Paralogs (1): NAPRT (ENSG00000147813)

Protein

Protein identifiers

Nicotinamide phosphoribosyltransferase — P43490 (reviewed: P43490)

Alternative names: Pre-B-cell colony-enhancing factor 1, Visfatin

All UniProt accessions (26): P43490, A0A0C4DFS8, A0A7P0T862, A0A7P0T895, A0A7P0T8D2, A0A7P0T8L3, A0A7P0T8R4, A0A7P0T8Z3, A0A7P0T931, A0A7P0T941, A0A7P0T973, A0A7P0T9F0, A0A7P0T9I9, A0A7P0TA73, A0A7P0TAI8, A0A7P0TAS5, A0A7P0TAZ2, A0A7P0TB17, A0A7P0TBB7, A0A7P0Z437, A0A7P0Z466, A0A7P0Z4L4, A0A7P0Z4N0, B7Z8W6, C9JF35, C9JG65

UniProt curated annotations — full annotation on UniProt →

Function. Catalyzes the condensation of nicotinamide 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 of clock target gene expression by releasing the core clock component: CLOCK-BMAL1 heterodimer from NAD-dependent SIRT1-mediated suppression.

Subunit / interactions. Homodimer.

Subcellular location. Nucleus. Cytoplasm. Secreted.

Tissue specificity. Expressed in large amounts in bone marrow, liver tissue, and muscle. Also present in heart, placenta, lung, and kidney tissues.

Activity regulation. Inhibited by FK866. FK866 competes for the same binding site as nicotinamide, but due to its very low dissociation rate, it is essentially an irreversible inhibitor.

Pathway. Cofactor biosynthesis; NAD(+) biosynthesis; nicotinamide D-ribonucleotide from 5-phospho-alpha-D-ribose 1-diphosphate and nicotinamide: step 1/1.

Similarity. Belongs to the NAPRTase family.

RefSeq proteins (1): NP_005737* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR013785	Aldolase_TIM	Homologous_superfamily
IPR016471	Nicotinamide_PRibTrfase	Family
IPR036068	Nicotinate_pribotase-like_C	Homologous_superfamily
IPR041525	N/Namide_PRibTrfase	Domain
IPR041529	DUF5598	Domain

Pfam: PF04095, PF18127

Enzyme classification (BRENDA):

• EC 2.4.2.12 — nicotinamide phosphoribosyltransferase (BRENDA: 7 organisms, 46 substrates, 542 inhibitors, 51 Km, 10 kcat entries)

Substrate kinetics (BRENDA)

7 substrates with measured Km, best-characterized 7. Km ranges are aggregated across organisms/conditions.

Substrate	Km (mM)	Measurements
NICOTINAMIDE	—	27
5-PHOSPHO-ALPHA-D-RIBOSE 1-DIPHOSPHATE	0.0001–0.78	15
ALPHA-D-5-PHOSPHORIBOSYL 1-DIPHOSPHATE	0.0006–0.0117	3
5-PHOSPHORIBOSYL 1-DIPHOSPHATE	0.0005–0.0232	2
ATP	2.2–7.4	2
ADP	0.44	1
PHOSPHATE	0.18	1

Catalyzed reactions (Rhea), 1 shown:

• beta-nicotinamide D-ribonucleotide + diphosphate = 5-phospho-alpha-D-ribose 1-diphosphate + nicotinamide + H(+) (RHEA:16149)

UniProt features (70 total): helix 26, strand 25, binding site 8, modified residue 3, mutagenesis site 3, turn 3, chain 1, sequence variant 1

Structure

Experimental structures (PDB)

84 structures, top 30 by resolution.

PDB	Method	Resolution (Å)
8DSC	X-RAY DIFFRACTION	1.32
8DSE	X-RAY DIFFRACTION	1.43
8DSD	X-RAY DIFFRACTION	1.43
8DSI	X-RAY DIFFRACTION	1.43
4LVF	X-RAY DIFFRACTION	1.5
6E68	X-RAY DIFFRACTION	1.5
4LVA	X-RAY DIFFRACTION	1.55
4O10	X-RAY DIFFRACTION	1.55
6TA0	X-RAY DIFFRACTION	1.58
4KFN	X-RAY DIFFRACTION	1.6
4KFO	X-RAY DIFFRACTION	1.6
5KIT	X-RAY DIFFRACTION	1.6
6TAC	X-RAY DIFFRACTION	1.6
4LWW	X-RAY DIFFRACTION	1.64
4O1B	X-RAY DIFFRACTION	1.65
6TA2	X-RAY DIFFRACTION	1.68
5UPF	X-RAY DIFFRACTION	1.69
4LTS	X-RAY DIFFRACTION	1.69
4N9D	X-RAY DIFFRACTION	1.7
4LVG	X-RAY DIFFRACTION	1.7
4O1D	X-RAY DIFFRACTION	1.71
4N9E	X-RAY DIFFRACTION	1.72
4WQ6	X-RAY DIFFRACTION	1.72
5U2N	X-RAY DIFFRACTION	1.73
7PPH	X-RAY DIFFRACTION	1.74
4LVD	X-RAY DIFFRACTION	1.75
4M6P	X-RAY DIFFRACTION	1.75
4O13	X-RAY DIFFRACTION	1.75
4O19	X-RAY DIFFRACTION	1.75
4N9C	X-RAY DIFFRACTION	1.75

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-P43490-F1	94.36	0.90

Functional residue map

Curated UniProt residues grouped by drug-discovery relevance — catalytic, ligand-binding, modification, and mutation-validated positions. Source: UniProtKB sequence features.

Ligand- & substrate-binding residues (8): 196; 219; 247; 311–313; 311; 353–354; 384; 392

Post-translational modifications (3): 188, 472, 1

Mutagenesis-validated functional residues (3):

Position	Phenotype
219	no effect on activity towards nicotinamide. alters specificity, so that the enzyme acquires activity towards nicotinic a
247	reduces activity towards nicotinamide.
311	reduces activity towards nicotinamide.

Function

Pathways and Gene Ontology

Reactome pathways

12 pathways

ID	Pathway
R-HSA-1368108	BMAL1:CLOCK,NPAS2 activates circadian expression
R-HSA-196807	Nicotinate metabolism
R-HSA-9768919	NPAS4 regulates expression of target genes
R-HSA-1430728	Metabolism
R-HSA-196849	Metabolism of water-soluble vitamins and cofactors
R-HSA-196854	Metabolism of vitamins and cofactors
R-HSA-197264
R-HSA-212436	Generic Transcription Pathway
R-HSA-400253
R-HSA-73857	RNA Polymerase II Transcription
R-HSA-74160	Gene expression (Transcription)
R-HSA-9634815	Transcriptional Regulation by NPAS4

MSigDB gene sets: 556 (showing top): GOBP_CIRCADIAN_RHYTHM, MODULE_92, GOBP_RESPONSE_TO_NITROGEN_COMPOUND, RODRIGUES_THYROID_CARCINOMA_ANAPLASTIC_UP, MCLACHLAN_DENTAL_CARIES_UP, RODRIGUES_THYROID_CARCINOMA_POORLY_DIFFERENTIATED_UP, GOBP_INFLAMMATORY_RESPONSE, GOBP_NADPPLUS_METABOLIC_PROCESS, MODULE_45, MODULE_64, GOBP_CANONICAL_NF_KAPPAB_SIGNAL_TRANSDUCTION, ROVERSI_GLIOMA_COPY_NUMBER_UP, MENSE_HYPOXIA_UP, GOBP_POSITIVE_REGULATION_OF_MAPK_CASCADE, GOBP_ORGANOPHOSPHATE_METABOLIC_PROCESS

GO Biological Process (17): NADP+ biosynthetic process (GO:0006741), nicotinamide metabolic process (GO:0006769), inflammatory response (GO:0006954), signal transduction (GO:0007165), cell-cell signaling (GO:0007267), positive regulation of cell population proliferation (GO:0008284), NAD+ biosynthetic process (GO:0009435), positive regulation of gene expression (GO:0010628), circadian regulation of gene expression (GO:0032922), NAD+ biosynthetic process via the salvage pathway (GO:0034355), positive regulation of canonical NF-kappaB signal transduction (GO:0043123), positive regulation of transcription by RNA polymerase II (GO:0045944), positive regulation of ERK1 and ERK2 cascade (GO:0070374), nicotinate metabolic process (GO:1901847), circadian rhythm (GO:0007623), pyridine nucleotide biosynthetic process (GO:0019363), rhythmic process (GO:0048511)

GO Molecular Function (6): cytokine activity (GO:0005125), identical protein binding (GO:0042802), nicotinamide phosphoribosyltransferase activity (GO:0047280), protein binding (GO:0005515), transferase activity (GO:0016740), glycosyltransferase activity (GO:0016757)

GO Cellular Component (9): mitochondrial matrix (GO:0005759), cytosol (GO:0005829), nuclear speck (GO:0016607), cell junction (GO:0030054), extracellular exosome (GO:0070062), extracellular region (GO:0005576), obsolete extracellular space (GO:0005615), nucleus (GO:0005634), cytoplasm (GO:0005737)

Reactome top-level categories

Rollup of top-8 pathways:

Category	Pathways
Circadian clock	1
Metabolism of water-soluble vitamins and cofactors	1
Transcriptional Regulation by NPAS4	1
Metabolism of vitamins and cofactors	1
Metabolism	1
RNA Polymerase II Transcription	1
Gene expression (Transcription)	1
Generic Transcription Pathway	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cellular anatomical structure	4
purine nucleotide biosynthetic process	2
nicotinamide nucleotide biosynthetic process	2
alkaloid metabolic process	2
pyridine-containing compound metabolic process	2
cell communication	2
signaling	2
regulation of gene expression	2
NADP+ metabolic process	1
defense response	1
cellular process	1
regulation of cellular process	1
cellular response to stimulus	1
cell population proliferation	1
regulation of cell population proliferation	1
positive regulation of cellular process	1
NAD+ metabolic process	1
gene expression	1
positive regulation of macromolecule biosynthetic process	1
circadian rhythm	1
NAD+ biosynthetic process	1
pyridine nucleotide salvage	1
purine nucleotide salvage	1
canonical NF-kappaB signal transduction	1
regulation of canonical NF-kappaB signal transduction	1
positive regulation of intracellular signal transduction	1
regulation of transcription by RNA polymerase II	1
transcription by RNA polymerase II	1
positive regulation of DNA-templated transcription	1
positive regulation of MAPK cascade	1
ERK1 and ERK2 cascade	1
regulation of ERK1 and ERK2 cascade	1
monocarboxylic acid metabolic process	1
rhythmic process	1
nucleotide biosynthetic process	1
pyridine-containing compound biosynthetic process	1
biological_process	1
receptor ligand activity	1
protein binding	1
pentosyltransferase activity	1

Protein interactions and networks

STRING

3251 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
NAMPT	NAPRT	Q6XQN6	949
NAMPT	SIRT1	Q96EB6	937
NAMPT	RETN	Q9HD89	915
NAMPT	NMNAT1	Q9HAN9	910
NAMPT	RETNLB	Q9BQ08	880
NAMPT	ADIPOQ	Q15848	876
NAMPT	LEP	P41159	840
NAMPT	CLOCK	O15516	822
NAMPT	ADIPOR2	Q86V24	822
NAMPT	BMAL1	O00327	806
NAMPT	RARRES2	Q99969	784
NAMPT	ADIPOR1	Q96A54	780
NAMPT	CMKLR2	P46091	779
NAMPT	PER2	O15055	774
NAMPT	ITLN1	Q8WWA0	774

IntAct

87 interactions, top by confidence:

A	B	Type	Score
NAMPT	NAMPT	psi-mi:“MI:0407”(direct interaction)	0.740
CFTR	ESYT2	psi-mi:“MI:0914”(association)	0.710
CFTR	ESYT2	psi-mi:“MI:2364”(proximity)	0.710
IGF1R	PIK3R2	psi-mi:“MI:2364”(proximity)	0.590
NAMPT	USP49	psi-mi:“MI:0915”(physical association)	0.560
IL13RA2	METTL15	psi-mi:“MI:0914”(association)	0.530
DNAAF8	CCDC85C	psi-mi:“MI:0914”(association)	0.530
NAMPT	MT-ND1	psi-mi:“MI:0915”(physical association)	0.510
NAMPT	FTL	psi-mi:“MI:0915”(physical association)	0.510
IFITM3	NAMPT	psi-mi:“MI:0915”(physical association)	0.510
FTL	NAMPT	psi-mi:“MI:0915”(physical association)	0.510
NAMPT	IFITM3	psi-mi:“MI:0915”(physical association)	0.510
MT-ND1	NAMPT	psi-mi:“MI:0915”(physical association)	0.510
CFTR	PLEKHG3	psi-mi:“MI:0914”(association)	0.480
CFTR	CNOT1	psi-mi:“MI:0914”(association)	0.480
XPO7	NAMPT	psi-mi:“MI:0915”(physical association)	0.400

BioGRID (171): NAMPT (Affinity Capture-RNA), NAMPT (Affinity Capture-MS), NAMPT (Affinity Capture-MS), NAMPT (Affinity Capture-MS), HSPB1 (Co-fractionation), NAMPT (Co-fractionation), NAPRT (Co-fractionation), NAMPT (Affinity Capture-MS), NAMPT (Affinity Capture-MS), NAMPT (Affinity Capture-MS), NAMPT (Affinity Capture-MS), NAMPT (Affinity Capture-MS), NAMPT (Affinity Capture-MS), NAMPT (Affinity Capture-MS), NAMPT (Affinity Capture-MS)

ESM2 similar proteins: A4FUD3, A7M6E7, A7M6E8, B9SQI7, E9Q4Z2, F4JGR5, O00763, O08810, O80526, O89000, P00367, P10860, P11497, P21343, P26443, P42174, P43490, P49448, P97789, Q0J035, Q13085, Q15029, Q28559, Q28EN2, Q32LQ4, Q41141, Q52I78, Q5F3X4, Q5M8Z0, Q5R6E0, Q5RAK7, Q5RFG2, Q5SWU9, Q5XGM3, Q5ZKY2, Q64514, Q64HZ9, Q6NYG8, Q6P6M7, Q803A7

Diamond homologs: A0A0H2X5R2, P43490, P75067, Q52I78, Q6FDK2, Q80Z29, Q99KQ4, P47283

SIGNOR signaling

5 interactions.

A	Effect	B	Mechanism
NAMPT	“up-regulates quantity”	NAD(1-)	“chemical modification”
PRKAA1	“up-regulates quantity”	NAMPT	“transcriptional regulation”
AMPK	“up-regulates quantity”	NAMPT
CLOCK/BMAL1	“up-regulates quantity by expression”	NAMPT	“transcriptional regulation”
NAMPT	down-regulates	CLOCK/BMAL1

Disease & clinical

Clinical variants and AI predictions

ClinVar

39 variants total. Per-class counts are floors (≥ shown; pagination cap):

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	16
Likely benign	2
Benign	4

Top pathogenic / likely-pathogenic (0)

SpliceAI

1516 predictions. Top by Δscore:

Variant	Effect	Δscore
7:106253015:A:AC	donor_gain	1.0000
7:106253016:C:CC	donor_gain	1.0000
7:106253016:CCTGA:C	donor_gain	1.0000
7:106253147:TTAAT:T	acceptor_gain	1.0000
7:106253148:TAAT:T	acceptor_gain	1.0000
7:106253149:AAT:A	acceptor_gain	1.0000
7:106253150:AT:A	acceptor_gain	1.0000
7:106253152:C:CC	acceptor_gain	1.0000
7:106253152:CTGAA:C	acceptor_loss	1.0000
7:106253159:CCAAA:C	acceptor_gain	1.0000
7:106253160:C:CT	acceptor_gain	1.0000
7:106253160:C:T	acceptor_gain	1.0000
7:106268458:TTTTA:T	donor_loss	1.0000
7:106268459:TTTAC:T	donor_loss	1.0000
7:106268460:TTA:T	donor_loss	1.0000
7:106268461:TACC:T	donor_loss	1.0000
7:106268462:ACC:A	donor_loss	1.0000
7:106268614:CA:C	acceptor_gain	1.0000
7:106268615:A:C	acceptor_gain	1.0000
7:106268621:C:CT	acceptor_gain	1.0000
7:106268622:A:T	acceptor_gain	1.0000
7:106268628:C:CT	acceptor_gain	1.0000
7:106269309:TAGT:T	acceptor_gain	1.0000
7:106269313:C:CC	acceptor_gain	1.0000
7:106272525:TTTA:T	donor_loss	1.0000
7:106272526:TTA:T	donor_loss	1.0000
7:106272527:TA:T	donor_loss	1.0000
7:106272528:A:AT	donor_loss	1.0000
7:106272529:C:G	donor_loss	1.0000
7:106272654:TACTT:T	acceptor_gain	1.0000

AlphaMissense

3225 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
7:106253137:C:A	K415N	0.999
7:106253137:C:G	K415N	0.999
7:106253139:T:C	K415E	0.999
7:106253144:A:T	V413D	0.999
7:106254388:G:C	S402R	0.999
7:106254388:G:T	S402R	0.999
7:106254390:T:G	S402R	0.999
7:106254391:A:C	C401W	0.999
7:106254394:C:A	K400N	0.999
7:106254394:C:G	K400N	0.999
7:106254396:T:C	K400E	0.999
7:106254418:T:A	R392S	0.999
7:106254418:T:G	R392S	0.999
7:106254419:C:A	R392I	0.999
7:106254419:C:G	R392T	0.999
7:106263527:G:C	S278R	0.999
7:106263527:G:T	S278R	0.999
7:106263529:T:G	S278R	0.999
7:106268466:G:C	H247Q	0.999
7:106268466:G:T	H247Q	0.999
7:106269173:C:A	R196I	0.999
7:106269173:C:G	R196T	0.999
7:106269181:A:C	F193L	0.999
7:106269181:A:T	F193L	0.999
7:106269183:A:G	F193L	0.999
7:106269294:A:G	W156R	0.999
7:106269294:A:T	W156R	0.999
7:106272531:T:A	E149V	0.999
7:106272550:A:G	W143R	0.999
7:106272550:A:T	W143R	0.999

dbSNP variants (sampled 300 via entrez): RS1000049205 (7:106281222 A>T), RS1000138635 (7:106262378 A>G), RS1000154597 (7:106276424 A>G), RS1000183552 (7:106286749 G>A), RS1000242945 (7:106255879 A>T), RS1000312532 (7:106253266 T>C), RS1000321050 (7:106286994 C>A), RS1000342518 (7:106249659 C>T), RS1000375152 (7:106249868 T>G), RS1000484593 (7:106276163 T>C), RS1000506611 (7:106254157 T>C), RS1000547744 (7:106281670 C>G,T), RS1000570068 (7:106265603 G>A,T), RS1000572320 (7:106255597 CTT>C), RS1000679492 (7:106248425 G>T)

Disease associations

OMIM: gene MIM:608764 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

0 total (0 of 0 shown, HPO-id order):

GWAS associations

2 associations (top):

Study	Trait	p-value
GCST008531_4	Grapefruit juice consumption	9.000000e-06
GCST012380_2	Eosinophilic esophagitis	1.000000e-08

EFO canonical traits (1, from GWAS)

EFO ID	Trait name
EFO:0010094	grapefruit juice consumption measurement

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (4): CHEMBL1744525 (SINGLE PROTEIN), CHEMBL5465234 (PROTEIN-PROTEIN INTERACTION), CHEMBL6066026 (PROTEIN-PROTEIN INTERACTION), CHEMBL6193845 (PROTEIN-PROTEIN INTERACTION)

Molecules with ChEMBL bioactivity

4 molecules (phase ≥1), by development phase (incl. off-target/promiscuous compounds). Patent mentions across the top 20 by phase: 3,471 (via chembl_molecule»patent_compound — counts attach to the compound, not the gene–compound relationship, so off-target/promiscuous molecules can dominate).

Molecule	Name	Phase	Patents
CHEMBL3621988	TUCIDINOSTAT	3	2,182
CHEMBL4297467	PADNARSERTIB	2	127
CHEMBL566757	DAPORINAD	2	593
CHEMBL17289	CHS-828	1	569

PharmGKB: 1 entry (VIP=true, CPIC=false)

PharmGKB variants

2 variants.

Variant	Genes	Level	Score	#Clin annots	Drugs
rs1319501	NAMPT		0.00	0
rs3801266	NAMPT		0.00	0

Binding affinities (BindingDB)

2748 measured of 3121 human assays (3121 total across all organisms); most potent 50 below. Values come from heterogeneous assays and are not directly comparable.

Ligand	Measure	Value	Patent
GMX1778	IC50	0.07 nM
APO-866	IC50	0.14 nM
MPI-0479883	IC50	0.17 nM
MPI-0479626	IC50	0.23 nM
1-cyano-2-[[4-(3,4-difluorophenyl)sulfonylphenyl]methyl]-3-pyridin-4-ylguanidine	IC50	0.8 nM	US-9676721: Compounds and compositions for the inhibition of NAMPT
N-[4-[4-[(2-cyclopropylacetyl)amino]cyclohexyl]phenyl]-1,3-dihydropyrrolo[3,4-c]pyridine-2-carboxamide	IC50	0.86 nM	US-9302989: NAMPT and rock inhibitors
N-[[5-[[6-(4-methylpiperazin-1-yl)-3-pyridinyl]sulfonyl]-2-pyridinyl]methyl]furo[2,3-c]pyridine-2-carboxamide	IC50	0.916 nM	US-9458172: Pyridinyl and pyrimidinyl sulfoxide and sulfone derivatives
N-[4-(1-benzoylpiperidin-4-yl)butyl]-5-cyano-1,3-dihydroisoindole-2-carboxamide	IC50	0.946 nM	US-9302989: NAMPT and rock inhibitors
N-[4-[4-(2-methylpropanoylamino)cyclohexyl]phenyl]-1,3-dihydropyrrolo[3,4-c]pyridine-2-carboxamide	IC50	0.973 nM	US-9302989: NAMPT and rock inhibitors
N-[[5-(3,5-dimethoxyphenyl)sulfonyl-2-pyridinyl]methyl]furo[2,3-c]pyridine-2-carboxamide	IC50	0.99 nM	US-9458172: Pyridinyl and pyrimidinyl sulfoxide and sulfone derivatives
2-[[4-[4-chloro-3-(trifluoromethyl)phenyl]sulfonylphenyl]methyl]-1-cyano-3-pyridin-4-ylguanidine	IC50	1 nM	US-9676721: Compounds and compositions for the inhibition of NAMPT
1-cyano-2-[[4-(3,5-difluorophenyl)sulfonylphenyl]methyl]-3-pyridin-4-ylguanidine	IC50	1 nM	US-9676721: Compounds and compositions for the inhibition of NAMPT
2-[2-[4-(benzenesulfonyl)phenyl]ethyl]-1-cyano-3-pyridin-4-ylguanidine	IC50	1 nM	US-9676721: Compounds and compositions for the inhibition of NAMPT
1-cyano-2-[[4-(3-fluoro-4-methoxyphenyl)sulfonylphenyl]methyl]-3-pyridin-4-ylguanidine	IC50	1 nM	US-9676721: Compounds and compositions for the inhibition of NAMPT
1-cyano-2-[[4-(1-methylindazol-6-yl)sulfonylphenyl]methyl]-3-pyridin-4-ylguanidine	IC50	1 nM	US-9676721: Compounds and compositions for the inhibition of NAMPT
1-cyano-3-pyridin-4-yl-2-[(4-quinolin-3-ylsulfonylphenyl)methyl]guanidine	IC50	1 nM	US-9676721: Compounds and compositions for the inhibition of NAMPT
N-[4-[1-(2,2-dimethylpropanoyl)-3,6-dihydro-2H-pyridin-4-yl]phenyl]-1,3-dihydropyrrolo[3,4-c]pyridine-2-carboxamide	IC50	1.03 nM	US-9302989: NAMPT and rock inhibitors
(E)-N-[4-(3-propan-2-yloxyphenyl)sulfonylphenyl]-3-pyridin-3-ylprop-2-enamide	IC50	1.1 nM	US-9169209: Compounds and compositions for the inhibition of NAMPT
1-cyano-2-[[4-(3-methoxy-4-methylphenyl)sulfonylphenyl]methyl]-3-pyridin-4-ylguanidine	IC50	1.2 nM	US-9676721: Compounds and compositions for the inhibition of NAMPT
5-cyano-N-[4-[1-(oxolane-3-carbonyl)-3,6-dihydro-2H-pyridin-4-yl]phenyl]-1,3-dihydroisoindole-2-carboxamide	IC50	1.22 nM	US-9302989: NAMPT and rock inhibitors
1-cyano-2-[[4-[3-(dimethylsulfamoyl)phenyl]sulfonylphenyl]methyl]-3-pyridin-4-ylguanidine	IC50	1.3 nM	US-9676721: Compounds and compositions for the inhibition of NAMPT
5-cyano-N-[4-[1-(oxane-4-carbonyl)-3,6-dihydro-2H-pyridin-4-yl]phenyl]-1,3-dihydroisoindole-2-carboxamide	IC50	1.34 nM	US-9302989: NAMPT and rock inhibitors
N-[4-[1-(2-hydroxy-2-methylbutanoyl)-3,6-dihydro-2H-pyridin-4-yl]phenyl]-1,3-dihydropyrrolo[3,4-c]pyridine-2-carboxamide	IC50	1.35 nM	US-9302989: NAMPT and rock inhibitors
N-[4-[1-(2,3-dimethylbutanoyl)-3,6-dihydro-2H-pyridin-4-yl]phenyl]-1,3-dihydropyrrolo[3,4-c]pyridine-2-carboxamide	IC50	1.37 nM	US-9302989: NAMPT and rock inhibitors
1-cyano-2-[[4-[(6-methyl-3-pyridinyl)sulfonyl]phenyl]methyl]-3-pyridin-4-ylguanidine	IC50	1.4 nM	US-9676721: Compounds and compositions for the inhibition of NAMPT
(E)-3-pyridin-3-yl-N-[4-[(5-pyrrolidin-1-yl-3-pyridinyl)sulfonyl]phenyl]prop-2-enamide	IC50	1.4 nM	US-9169209: Compounds and compositions for the inhibition of NAMPT
5-cyano-N-[4-[1-(2-methylpropanoyl)-3,6-dihydro-2H-pyridin-4-yl]phenyl]-1,3-dihydroisoindole-2-carboxamide	IC50	1.44 nM	US-9302989: NAMPT and rock inhibitors
N-[4-(1-benzoylpiperidin-4-yl)phenyl]-1,3-dihydroisoindole-2-carboxamide	IC50	1.45 nM	US-9302989: NAMPT and rock inhibitors
N-[4-[1-(1,5-dimethylpyrazole-3-carbonyl)-3,6-dihydro-2H-pyridin-4-yl]phenyl]-1,3-dihydropyrrolo[3,4-c]pyridine-2-carboxamide	IC50	1.49 nM	US-9302989: NAMPT and rock inhibitors
1-cyano-2-[[4-(3-methoxyphenyl)sulfonylphenyl]methyl]-3-pyridin-4-ylguanidine	IC50	1.5 nM	US-9676721: Compounds and compositions for the inhibition of NAMPT
1-cyano-2-[[4-(4-morpholin-4-ylphenyl)sulfonylphenyl]methyl]-3-pyridin-4-ylguanidine	IC50	1.5 nM	US-9676721: Compounds and compositions for the inhibition of NAMPT
N-[4-[1-(2-methyl-1,3-oxazole-4-carbonyl)-3,6-dihydro-2H-pyridin-4-yl]phenyl]-1,3-dihydropyrrolo[3,4-c]pyridine-2-carboxamide	IC50	1.5 nM	US-9302989: NAMPT and rock inhibitors
5-cyano-N-[4-[1-(2-hydroxy-2-methylpropanoyl)-3,6-dihydro-2H-pyridin-4-yl]phenyl]-1,3-dihydroisoindole-2-carboxamide	IC50	1.51 nM	US-9302989: NAMPT and rock inhibitors
N-[4-[1-(2-cyclopropylacetyl)-3,6-dihydro-2H-pyridin-4-yl]phenyl]-1,3-dihydropyrrolo[3,4-c]pyridine-2-carboxamide	IC50	1.52 nM	US-9302989: NAMPT and rock inhibitors
N-[4-[1-(3-hydroxy-3-methylbutanoyl)-3,6-dihydro-2H-pyridin-4-yl]phenyl]-1,3-dihydropyrrolo[3,4-c]pyridine-2-carboxamide	IC50	1.53 nM	US-9302989: NAMPT and rock inhibitors
N-[4-[1-(4-methylhexanoyl)-3,6-dihydro-2H-pyridin-4-yl]phenyl]-1,3-dihydropyrrolo[3,4-c]pyridine-2-carboxamide	IC50	1.55 nM	US-9302989: NAMPT and rock inhibitors
N-[4-(1-benzoylpyrrolidin-3-yl)oxyphenyl]-1,3-dihydropyrrolo[3,4-c]pyridine-2-carboxamide	IC50	1.57 nM	US-9302989: NAMPT and rock inhibitors
N-[4-(1-benzoylpiperidin-4-yl)butyl]-1,3-dihydropyrrolo[3,4-c]pyridine-2-carboxamide	IC50	1.57 nM	US-9302989: NAMPT and rock inhibitors
5-cyano-N-[4-[(2-cyclopentylacetyl)amino]phenyl]-1,3-dihydroisoindole-2-carboxamide	IC50	1.59 nM	US-9302989: NAMPT and rock inhibitors
N-[4-[1-(1-methylpyrrole-2-carbonyl)-3,6-dihydro-2H-pyridin-4-yl]phenyl]-1,3-dihydropyrrolo[3,4-c]pyridine-2-carboxamide	IC50	1.59 nM	US-9302989: NAMPT and rock inhibitors
N-[4-[(2-cyclopentylacetyl)amino]phenyl]-5-pyridin-4-yl-1,3-dihydroisoindole-2-carboxamide	IC50	1.59 nM	US-9302989: NAMPT and rock inhibitors
5-bromo-N-[4-[(2-cyclopentylacetyl)amino]phenyl]-1,3-dihydroisoindole-2-carboxamide	IC50	1.66 nM	US-9302989: NAMPT and rock inhibitors
N-[4-[1-(2,2-dimethylcyclopropanecarbonyl)-3,6-dihydro-2H-pyridin-4-yl]phenyl]-1,3-dihydropyrrolo[3,4-c]pyridine-2-carboxamide	IC50	1.68 nM	US-9302989: NAMPT and rock inhibitors
N-[4-[(2-cyclopentylacetyl)amino]phenyl]-1,3-dihydropyrrolo[3,4-c]pyridine-2-carboxamide	IC50	1.68 nM	US-9302989: NAMPT and rock inhibitors
2-N-[4-[(2-cyclopentylacetyl)amino]phenyl]-5-N-(2-methoxyethyl)-1,3-dihydroisoindole-2,5-dicarboxamide	IC50	1.69 nM	US-9302989: NAMPT and rock inhibitors
1-cyano-2-[[4-(3,4-dichlorophenyl)sulfonylphenyl]methyl]-3-pyridin-4-ylguanidine	IC50	1.7 nM	US-9676721: Compounds and compositions for the inhibition of NAMPT
1-cyano-2-[[4-[3-(morpholine-4-carbonyl)phenyl]sulfonylphenyl]methyl]-3-pyridin-4-ylguanidine	IC50	1.7 nM	US-9676721: Compounds and compositions for the inhibition of NAMPT
1-cyano-2-[[4-(3-cyanophenyl)sulfonylphenyl]methyl]-3-pyridin-4-ylguanidine	IC50	1.7 nM	US-9676721: Compounds and compositions for the inhibition of NAMPT
1-cyano-2-[[4-(3-fluoro-5-methylphenyl)sulfonylphenyl]methyl]-3-pyridin-4-ylguanidine	IC50	1.7 nM	US-9676721: Compounds and compositions for the inhibition of NAMPT
N-[[5-[(6-morpholin-4-yl-3-pyridinyl)sulfonyl]-2-pyridinyl]methyl]thieno[2,3-c]pyridine-2-carboxamide	IC50	1.7 nM	US-9458172: Pyridinyl and pyrimidinyl sulfoxide and sulfone derivatives

ChEMBL bioactivities

5525 potent at pChembl≥5 of 5648 total, top 50 by pChembl (potency: 10 = 0.1 nM, 6 = 1 µM).

pChembl	Type	Value	Unit	Molecule
10.52	IC50	0.0301	nM	DAPORINAD
10.29	IC50	0.0509	nM	CHEMBL3753643
10.00	IC50	0.1	nM	CHEMBL5750961
9.82	IC50	0.15	nM	DAPORINAD
9.82	IC50	0.15	nM	CHEMBL5429026
9.81	IC50	0.155	nM	CHEMBL4544378
9.80	IC50	0.16	nM	CHEMBL5437893
9.76	IC50	0.174	nM	CHEMBL3260316
9.70	IC50	0.2	nM	CHEMBL3094250
9.70	Ki	0.2	nM	DAPORINAD
9.70	Ki	0.2	nM	CHEMBL4440516
9.64	IC50	0.23	nM	CHEMBL2417796
9.64	IC50	0.23	nM	CHEMBL5572833
9.52	IC50	0.3	nM	CHEMBL1801863
9.52	Ki	0.3	nM	DAPORINAD
9.52	IC50	0.3	nM	CHEMBL3094255
9.52	IC50	0.3	nM	CHEMBL5825361
9.52	IC50	0.3	nM	CHEMBL5816481
9.51	IC50	0.31	nM	CHEMBL123756
9.40	IC50	0.4	nM	CHEMBL3968268
9.38	IC50	0.412	nM	CHEMBL3260317
9.35	IC50	0.45	nM	CHEMBL1801864
9.34	IC50	0.461	nM	CHEMBL3260314
9.30	IC50	0.5	nM	CHEMBL1801864
9.30	IC50	0.5	nM	CHEMBL5774398
9.26	IC50	0.55	nM	CHEMBL1801934
9.25	IC50	0.56	nM	DAPORINAD
9.22	IC50	0.6	nM	CHEMBL3098518
9.22	IC50	0.6	nM	CHEMBL3916438
9.22	IC50	0.6	nM	CHEMBL5995645
9.20	IC50	0.632	nM	CHEMBL3260315
9.20	EC50	0.63	nM	CHEMBL5434442
9.15	IC50	0.7	nM	CHEMBL5982902
9.10	IC50	0.8	nM	CHEMBL5799317
9.10	IC50	0.8	nM	CHEMBL5998092
9.10	IC50	0.8	nM	CHEMBL5764220
9.10	IC50	0.79	nM	CHEMBL1801862
9.07	IC50	0.86	nM	CHEMBL3900725
9.05	IC50	0.9	nM	CHEMBL6005980
9.05	IC50	0.9	nM	CHEMBL5746218
9.05	IC50	0.9	nM	CHEMBL5748396
9.05	IC50	0.9	nM	CHEMBL5869571
9.05	IC50	0.9	nM	CHEMBL6054737
9.04	IC50	0.916	nM	CHEMBL3914799
9.02	IC50	0.946	nM	CHEMBL3919342
9.01	IC50	0.973	nM	CHEMBL3900838
9.00	IC50	1	nM	CHEMBL2420634
9.00	IC50	1	nM	CHEMBL2420633
9.00	IC50	1	nM	CHS-828
9.00	IC50	1	nM	DAPORINAD

PubChem BioAssay actives

1086 with measured affinity, of 2062 total; 50 most potent distinct compounds. Largely complementary to BindingDB; screening values are coarse (µM, 4 dp), so sub-nM hits tie at the floor.

Compound	Assay	Type	Value	Unit
(E)-N-[4-[1-[3-[bis(2-chloroethyl)amino]benzoyl]piperidin-4-yl]butyl]-3-pyridin-3-ylprop-2-enamide	2004628: Inhibition of recombinant human NAMPT preincubated for 5 mins followed by NAM addition measured for 15 mins by fluorescence based assay	ic50	0.0001	uM
2-[6-(4-chlorophenoxy)hexyl]-1-cyano-3-pyridin-4-ylguanidine	1799546: In Vitro Inhibition Assay from Article 10.1016/j.chembiol.2010.05.008: “Chemical proteomics identifies Nampt as the target of CB30865, an orphan cytotoxic compound.”	ic50	0.0001	uM
(E)-N-[4-(1-benzoylpiperidin-4-yl)butyl]-3-pyridin-3-ylprop-2-enamide	1799546: In Vitro Inhibition Assay from Article 10.1016/j.chembiol.2010.05.008: “Chemical proteomics identifies Nampt as the target of CB30865, an orphan cytotoxic compound.”	ic50	0.0001	uM
(E)-N-[5-[4-[[2-(1H-indol-3-yl)ethyl-propan-2-ylamino]methyl]anilino]pentyl]-3-pyridin-3-ylprop-2-enamide	1625940: Inhibition of NAMPT in human MCF7 cells assessed as decrease in NAD production after 24 hrs by NAD/NADH Glo assay	ic50	0.0002	uM
(E)-N-[4-[1-[2-[bis(2-chloroethyl)amino]benzoyl]piperidin-4-yl]butyl]-3-pyridin-3-ylprop-2-enamide	2004628: Inhibition of recombinant human NAMPT preincubated for 5 mins followed by NAM addition measured for 15 mins by fluorescence based assay	ic50	0.0002	uM
tert-butyl N-[2-[2-[2-oxo-2-[[3-[4-[4-[[(E)-3-pyridin-3-ylprop-2-enoyl]amino]butyl]piperidine-1-carbonyl]phenyl]methylamino]ethoxy]ethoxy]ethyl]carbamate	1515664: Displacement of fluorescent labelled OG488 from human full length FLAG-tagged NAMPT (1 to 491 residues) expressed in HEK293-6E cells in presence of PRPP by TR-FRET assay	ki	0.0002	uM
7-[[(cyanoamino)-(pyridin-4-ylamino)methylidene]amino]-N-cyclohexyl-N-(2-morpholin-4-ylethoxy)heptanamide	1057516: Inhibition of NAMPT in human HepG2 cells using [14C]-nicotinamide/PRPP as substrate assessed as formation of [14C]-nicotinamide mononucleotide after 1 hr by liquid scintillation counting analysis	ic50	0.0002	uM
4-[[2-[[4-(2-aminoethyl)piperazin-1-yl]methyl]-7-chloro-3-methyl-4-oxoquinazolin-6-yl]methyl-prop-2-ynylamino]-N-(pyridin-3-ylmethyl)benzamide	1799546: In Vitro Inhibition Assay from Article 10.1016/j.chembiol.2010.05.008: “Chemical proteomics identifies Nampt as the target of CB30865, an orphan cytotoxic compound.”	ic50	0.0002	uM
N-(3-imidazol-1-ylpropyl)-2-[3-methylbutyl-(2-phenoxyacetyl)amino]-1,3-thiazole-5-carboxamide	1137945: Inhibition of recombinant human C-terminally His-tagged NAMPT by TR-FRET assay in presence of PRPP	ic50	0.0002	uM
4-[[7-bromo-3-methyl-2-[(4-methylpiperazin-1-yl)methyl]-4-oxoquinazolin-6-yl]methyl-prop-2-ynylamino]-N-(pyridin-3-ylmethyl)benzamide	767963: Inhibition of NAMPT (unknown origin)	ic50	0.0002	uM
4-[[7-chloro-3-methyl-2-[(4-methylpiperazin-1-yl)methyl]-4-oxoquinazolin-6-yl]methyl-prop-2-ynylamino]-N-(pyridin-3-ylmethyl)benzamide	1799546: In Vitro Inhibition Assay from Article 10.1016/j.chembiol.2010.05.008: “Chemical proteomics identifies Nampt as the target of CB30865, an orphan cytotoxic compound.”	ic50	0.0002	uM
1-cyano-2-[6-[cyclohexyl(2-morpholin-4-ylethoxy)sulfamoyl]hexyl]-3-pyridin-4-ylguanidine	1057516: Inhibition of NAMPT in human HepG2 cells using [14C]-nicotinamide/PRPP as substrate assessed as formation of [14C]-nicotinamide mononucleotide after 1 hr by liquid scintillation counting analysis	ic50	0.0003	uM
4-[[2-[[4-(3-aminopropyl)piperazin-1-yl]methyl]-7-chloro-3-methyl-4-oxoquinazolin-6-yl]methyl-prop-2-ynylamino]-N-(pyridin-3-ylmethyl)benzamide	604933: Inhibition of nicotinamide phosphoribosyltransferase-catalyzed conversion of nicotinamide to nicotinamide mononucleotide	ic50	0.0003	uM
4-[(7-chloro-3-methyl-4-oxo-1,2,3-benzotriazin-6-yl)methyl-(3-methylbut-2-enyl)amino]-N-(pyridin-3-ylmethyl)benzamide	604933: Inhibition of nicotinamide phosphoribosyltransferase-catalyzed conversion of nicotinamide to nicotinamide mononucleotide	ic50	0.0004	uM
N-[[6-[2-(4-methyloxan-4-yl)acetyl]-6-azaspiro[2.5]octan-2-yl]methyl]-1,3-dihydropyrrolo[3,4-c]pyridine-2-carboxamide	1327638: Inhibition of NAMPT in human A2780 cells assessed as decrease in cell viability after 72 hrs by SRB assay	ic50	0.0004	uM
N-(3-imidazol-1-ylpropyl)-2-[(2-methoxyacetyl)-(3-methylbutyl)amino]-1,3-thiazole-5-carboxamide	1137945: Inhibition of recombinant human C-terminally His-tagged NAMPT by TR-FRET assay in presence of PRPP	ic50	0.0004	uM
2-[(2-cyclohexylacetyl)-[(4-fluorophenyl)methyl]amino]-N-(3-imidazol-1-ylpropyl)-1,3-thiazole-5-carboxamide	1137945: Inhibition of recombinant human C-terminally His-tagged NAMPT by TR-FRET assay in presence of PRPP	ic50	0.0005	uM
(2S,4R)-1-[(2S)-3,3-dimethyl-2-[[2-[2-[2-[2-[2-[[4-[[4-[4-(pyridin-3-ylmethylcarbamothioylamino)phenyl]sulfonylpiperazin-1-yl]methyl]benzoyl]amino]ethoxy]ethoxy]ethoxy]ethoxy]acetyl]amino]butanoyl]-4-hydroxy-N-[(1S)-1-[4-(4-methyl-1,3-thiazol-5-yl)phenyl]ethyl]pyrrolidine-2-carboxamide	2012074: PROTAC activity at VHL/NAMPT in human A2780 cells assessed as protein degradation	ec50	0.0006	uM
4-[(7-chloro-2,3-dimethyl-4-oxoquinazolin-6-yl)methyl-prop-2-ynylamino]-N-(pyridin-3-ylmethyl)benzamide	604933: Inhibition of nicotinamide phosphoribosyltransferase-catalyzed conversion of nicotinamide to nicotinamide mononucleotide	ic50	0.0006	uM
1-cyano-2-[[4-(3,5-difluorophenyl)sulfonylphenyl]methyl]-3-pyridin-4-ylguanidine	1060645: Inhibition of Nampt (unknown origin) using nicotinamide as substrate preincubated for 15 mins measured after 30 mins by mass spectrometry analysis	ic50	0.0006	uM
2-[[2-(3,6-dihydro-2H-pyridin-1-yl)acetyl]-[(4-fluorophenyl)methyl]amino]-N-(3-imidazol-1-ylpropyl)-1,3-thiazole-5-carboxamide	1137945: Inhibition of recombinant human C-terminally His-tagged NAMPT by TR-FRET assay in presence of PRPP	ic50	0.0006	uM
(3-methyloxetan-3-yl) (2S)-2-[(1,3-dihydropyrrolo[3,4-c]pyridine-2-carbonylamino)methyl]-6-azaspiro[2.5]octane-6-carboxylate	1327638: Inhibition of NAMPT in human A2780 cells assessed as decrease in cell viability after 72 hrs by SRB assay	ic50	0.0006	uM
4-[[7-chloro-2-(hydroxymethyl)-3-methyl-4-oxoquinazolin-6-yl]methyl-prop-2-ynylamino]-N-(pyridin-3-ylmethyl)benzamide	604933: Inhibition of nicotinamide phosphoribosyltransferase-catalyzed conversion of nicotinamide to nicotinamide mononucleotide	ic50	0.0008	uM
(3-methyloxetan-3-yl) 2-[[(1,1,3,3-tetradeuteriopyrrolo[3,4-c]pyridine-2-carbonyl)amino]methyl]-6-azaspiro[2.5]octane-6-carboxylate	1327638: Inhibition of NAMPT in human A2780 cells assessed as decrease in cell viability after 72 hrs by SRB assay	ic50	0.0010	uM
tert-butyl (2S)-2-[(1,3-dihydropyrrolo[3,4-c]pyridine-2-carbonylamino)methyl]-6-azaspiro[2.5]octane-6-carboxylate	1327638: Inhibition of NAMPT in human A2780 cells assessed as decrease in cell viability after 72 hrs by SRB assay	ic50	0.0010	uM
trans-(1S,2S)-N-[4-[(1,3-dioxoisoindol-2-yl)methyl]phenyl]-2-pyridin-3-ylcyclopropane-1-carboxamide	1370711: Inhibition of full length recombinant C-terminal His8-tagged human NAMPT using 15N-CONH2Nicotinamide as substrate preincubated for 15 mins followed by substrate addition measured after 90 mins by mass spectrometric analysis	ic50	0.0010	uM
4-[(7-bromo-2-methyl-4-oxo-3H-quinazolin-6-yl)methyl-prop-2-ynylamino]-N-(pyridin-3-ylmethyl)benzamide	2106995: Inhibition of N-terminal His-tagged human NAMPT	ic50	0.0010	uM
N-[4-(1-benzoylpiperidin-4-yl)phenyl]-1,3-dihydroisoindole-2-carboxamide	1454317: Inhibition of C-terminal His-tagged human recombinant NAMPT using FK866 or isoindoline urea-based Oregon green (488) probe incubated for 3 hrs by TR-FRET assay	ki	0.0010	uM
N-[[4-[3-(trifluoromethyl)phenyl]sulfonylphenyl]methyl]imidazo[1,2-a]pyrimidine-6-carboxamide	765316: Inhibition of C-terminal His-tagged NAMPT (unknown origin) expressed in Escherichia coli BL21 using nicotinamide as substrate preincubated for 15 mins before substrate addition measured after 30 mins by mass spectrometry-based assay	ic50	0.0010	uM
N-[[4-[(6-morpholin-4-yl-3-pyridinyl)sulfonyl]phenyl]methyl]imidazo[1,2-a]pyrimidine-6-carboxamide	765316: Inhibition of C-terminal His-tagged NAMPT (unknown origin) expressed in Escherichia coli BL21 using nicotinamide as substrate preincubated for 15 mins before substrate addition measured after 30 mins by mass spectrometry-based assay	ic50	0.0010	uM
(3S)-1-[2-(4-methylphenyl)pyrazolo[3,4-d]pyrimidin-4-yl]-N-[(4-methylsulfanylphenyl)methyl]piperidine-3-carboxamide	2106990: Activation of C-terminal 6His-tagged human wild type NAMPT using NAM and PRPP as substrate measured for 30 mins in presence of ATP by fluorescence based spectrometric analysis	ec50	0.0010	uM
(E)-N-[4-[1-[4-[bis(2-chloroethyl)amino]benzoyl]piperidin-4-yl]butyl]-3-pyridin-3-ylprop-2-enamide	2004628: Inhibition of recombinant human NAMPT preincubated for 5 mins followed by NAM addition measured for 15 mins by fluorescence based assay	ic50	0.0011	uM
(E)-N-[4-[1-[3-(aminomethyl)benzoyl]piperidin-4-yl]butyl]-3-pyridin-3-ylprop-2-enamide	1515664: Displacement of fluorescent labelled OG488 from human full length FLAG-tagged NAMPT (1 to 491 residues) expressed in HEK293-6E cells in presence of PRPP by TR-FRET assay	ki	0.0011	uM
7-[[(cyanoamino)-(pyridin-4-ylamino)methylidene]amino]-N-cyclohexyloxyheptanamide	1057516: Inhibition of NAMPT in human HepG2 cells using [14C]-nicotinamide/PRPP as substrate assessed as formation of [14C]-nicotinamide mononucleotide after 1 hr by liquid scintillation counting analysis	ic50	0.0011	uM
N-[[4-(3,5-difluorophenyl)sulfonylphenyl]methyl]imidazo[1,2-a]pyridine-6-carboxamide	1137989: Inhibition of NAMPT in human PC3 cells assessed as reduction in NAD level after 48 hrs by mass spectrometry	ec50	0.0011	uM
(3S)-N-(1-benzothiophen-5-ylmethyl)-1-[2-[4-(trifluoromethyl)phenyl]pyrazolo[3,4-d]pyrimidin-4-yl]piperidine-3-carboxamide	2106990: Activation of C-terminal 6His-tagged human wild type NAMPT using NAM and PRPP as substrate measured for 30 mins in presence of ATP by fluorescence based spectrometric analysis	ec50	0.0012	uM
4-[3-methylbut-2-enyl-[(3-methyl-4-oxoquinazolin-6-yl)methyl]amino]-N-(pyridin-3-ylmethyl)benzamide	604933: Inhibition of nicotinamide phosphoribosyltransferase-catalyzed conversion of nicotinamide to nicotinamide mononucleotide	ic50	0.0012	uM
1-(pyridin-3-ylmethyl)-3-[4-[2-(trifluoromethoxy)phenyl]sulfonylphenyl]urea	767963: Inhibition of NAMPT (unknown origin)	ic50	0.0012	uM
N-[[4-[3-(trifluoromethyl)phenyl]sulfonylphenyl]methyl]-1H-pyrazolo[3,4-b]pyridine-5-carboxamide	1137989: Inhibition of NAMPT in human PC3 cells assessed as reduction in NAD level after 48 hrs by mass spectrometry	ec50	0.0012	uM
4-[1-[2-[bis(2-chloroethyl)amino]benzoyl]piperidin-4-yl]butyl (E)-3-pyridin-3-ylprop-2-enoate	2004628: Inhibition of recombinant human NAMPT preincubated for 5 mins followed by NAM addition measured for 15 mins by fluorescence based assay	ic50	0.0013	uM
3-[(2E)-2-[(2E,4E)-5-[3,3-dimethyl-5-sulfo-1-(3-sulfopropyl)indol-1-ium-2-yl]penta-2,4-dienylidene]-3-methyl-3-[6-oxo-6-[2-[2-[2-oxo-2-[[3-[4-[4-[[(E)-3-pyridin-3-ylprop-2-enoyl]amino]butyl]piperidine-1-carbonyl]phenyl]methylamino]ethoxy]ethoxy]ethylamino]hexyl]-5-sulfoindol-1-yl]propane-1-sulfonate	1515664: Displacement of fluorescent labelled OG488 from human full length FLAG-tagged NAMPT (1 to 491 residues) expressed in HEK293-6E cells in presence of PRPP by TR-FRET assay	ki	0.0013	uM
4-[(2-chlorophenyl)methyl-(cyclopropylmethyl)amino]-N-(pyridin-3-ylmethyl)benzamide	604933: Inhibition of nicotinamide phosphoribosyltransferase-catalyzed conversion of nicotinamide to nicotinamide mononucleotide	ic50	0.0013	uM
4-[(2,3-dimethyl-4-oxoquinazolin-6-yl)methyl-(3-methylbut-2-enyl)amino]-N-(pyridin-3-ylmethyl)benzamide	604933: Inhibition of nicotinamide phosphoribosyltransferase-catalyzed conversion of nicotinamide to nicotinamide mononucleotide	ic50	0.0014	uM
N-[4-[1-[2-methyl-2-(4-methylpiperazin-1-yl)propanoyl]piperidin-4-yl]phenyl]-1,3-dihydroisoindole-2-carboxamide	1454317: Inhibition of C-terminal His-tagged human recombinant NAMPT using FK866 or isoindoline urea-based Oregon green (488) probe incubated for 3 hrs by TR-FRET assay	ki	0.0015	uM
(2S,4R)-1-[(2S)-3,3-dimethyl-2-[11-[[4-[4-[4-[[(E)-3-pyridin-3-ylprop-2-enoyl]amino]butyl]piperidine-1-carbonyl]benzoyl]amino]undecanoylamino]butanoyl]-4-hydroxy-N-[(1S)-1-[4-(4-methyl-1,3-thiazol-5-yl)phenyl]ethyl]pyrrolidine-2-carboxamide	2012073: Inhibition of NAMPT (unknown origin)	ic50	0.0015	uM
(2S,4R)-1-[(2S)-3,3-dimethyl-2-[4-[[4-[4-[4-[[(E)-3-pyridin-3-ylprop-2-enoyl]amino]butyl]piperidine-1-carbonyl]benzoyl]amino]butanoylamino]butanoyl]-4-hydroxy-N-[(1S)-1-[4-(4-methyl-1,3-thiazol-5-yl)phenyl]ethyl]pyrrolidine-2-carboxamide	2012073: Inhibition of NAMPT (unknown origin)	ic50	0.0015	uM
4-[[(E)-but-2-enyl]-[(2-chlorophenyl)methyl]amino]-N-(pyridin-3-ylmethyl)benzamide	604933: Inhibition of nicotinamide phosphoribosyltransferase-catalyzed conversion of nicotinamide to nicotinamide mononucleotide	ic50	0.0015	uM
N-[[6-(2,4-dimethyl-1,3-oxazole-5-carbonyl)-6-azaspiro[2.5]octan-2-yl]methyl]-1,3-dihydropyrrolo[3,4-c]pyridine-2-carboxamide	1327638: Inhibition of NAMPT in human A2780 cells assessed as decrease in cell viability after 72 hrs by SRB assay	ic50	0.0016	uM
N-[[6-(3,3-dimethylbutanoyl)-6-azaspiro[2.5]octan-2-yl]methyl]-1,3-dihydropyrrolo[3,4-c]pyridine-2-carboxamide	1327638: Inhibition of NAMPT in human A2780 cells assessed as decrease in cell viability after 72 hrs by SRB assay	ic50	0.0016	uM
(1-methoxy-2-methylpropan-2-yl) 2-[(1,3-dihydropyrrolo[3,4-c]pyridine-2-carbonylamino)methyl]-6-azaspiro[2.5]octane-6-carboxylate	1327638: Inhibition of NAMPT in human A2780 cells assessed as decrease in cell viability after 72 hrs by SRB assay	ic50	0.0016	uM

CTD chemical–gene interactions

140 total (human), top 30 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
sodium arsenite	affects cotreatment, increases abundance, increases expression, increases stability	4
N-(4-(1-benzoylpiperidin-4-yl)butyl)-3-(pyridin-3-yl)acrylamide	decreases expression, increases reaction, affects binding, decreases activity, increases abundance	3
Cisplatin	affects response to substance, affects cotreatment, increases expression	3
Dinitrochlorobenzene	affects binding, increases expression	3
Lipopolysaccharides	decreases reaction, increases expression, affects response to substance, affects cotreatment	3
Rotenone	decreases expression, increases expression, decreases activity	3
Tobacco Smoke Pollution	affects expression, increases expression	3
Valproic Acid	affects cotreatment, decreases expression	3
Cyclosporine	increases expression	3
Cadmium Chloride	increases expression, increases abundance	3
Particulate Matter	increases abundance, increases expression, decreases expression	3
bisphenol A	affects expression, decreases expression	2
manganese chloride	increases expression, affects cotreatment, increases abundance	2
Rosiglitazone	affects expression, decreases reaction, increases expression	2
Resveratrol	decreases activity, increases secretion, increases acetylation, decreases reaction, increases activity (+2 more)	2
Zoledronic Acid	increases expression	2
Benzo(a)pyrene	increases expression	2
Dexamethasone	decreases expression, increases expression	2
Doxorubicin	affects expression, decreases expression	2
Estradiol	affects expression, increases abundance, increases reaction	2
Glucose	increases secretion, decreases expression, increases expression, decreases reaction	2
Manganese	increases expression, affects cotreatment, increases abundance	2
Nickel	increases expression	2
Testosterone	affects cotreatment, increases expression, decreases expression	2
Tetrachlorodibenzodioxin	increases expression	2
Dronabinol	increases expression	2
Thiram	decreases expression, increases expression	2
Tretinoin	increases expression	2
7,8-Dihydro-7,8-dihydroxybenzo(a)pyrene 9,10-oxide	decreases expression	2
aristolochic acid I	decreases expression, increases expression	1

ChEMBL screening assays

299 unique, capped per target: 299 binding

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL1763209	Binding	Inhibition of human NAmPRTase by spectrophotometric analysis	Design, synthesis and X-ray crystallographic study of NAmPRTase inhibitors as anti-cancer agents. — Eur J Med Chem

Cellosaurus cell lines

3 cell lines: 3 cancer cell line

First 10 cell lines (id-ordered, not curated):

Cellosaurus	Name	Category	Sex
CVCL_D1XP	Abcam A-549 NAMPT KO	Cancer cell line	Male
CVCL_D2C0	Abcam HCT 116 NAMPT KO	Cancer cell line	Male
CVCL_D2NQ	Abcam THP-1 NAMPT KO	Cancer cell line	Male

Clinical trials (associated diseases)

0 trials via MONDO — disease-level, not drug-specific.