Affinage

NAMPT

Nicotinamide phosphoribosyltransferase · UniProt P43490

Length
491 aa
Mass
55.5 kDa
Annotated
2026-06-10
100 papers in source corpus 34 papers cited in narrative 36 extracted findings
Cross-family judge vs UniProt: Affinage preferred faithfulness: 5/5 claims corpus-supported (100%)

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

NAMPT is the rate-limiting enzyme of the mammalian NAD+ salvage pathway, a dimeric type II phosphoribosyltransferase that converts nicotinamide to nicotinamide mononucleotide (NMN) using PRPP, sustaining cellular and systemic NAD+ pools that govern diverse metabolic and inflammatory programs (PMID:16783373, PMID:17268245, PMID:17983582). By providing the NAD+ that drives NAD+-dependent enzymes, intracellular NAMPT controls glucose-stimulated insulin secretion in pancreatic islets (PMID:17983582), supports SIRT1- and PARP1-dependent signaling (PMID:23435312), fuels macrophage glycolysis, HIF-1α stabilization, and the NADPH-dependent oxidative burst needed for phagocytosis and efferocytosis (PMID:35063804, PMID:38308188), promotes CD4+ T cell IFNγ production through aerobic glycolysis and Ifng translation (PMID:36146932), and maintains neuronal mitochondrial integrity (PMID:36441480). The enzyme's activity is regulated allosterically through a rear-channel binding site that relieves NAM/NAD+ feedback inhibition (PMID:38096366) and post-translationally by AMPK-mediated Ser314 phosphorylation, which enhances PRPP binding to restore NAD+ for DNA repair (PMID:36196536), and by SIRT1-mediated deacetylation that boosts catalytic activity (PMID:36797299). NAMPT also functions extracellularly: hepatocytes and glucose-stimulated islets secrete an enzymatically active dimeric form (PMID:19912992, PMID:23536823), which acts as a pro-inflammatory mediator that requires its enzymatic activity to drive MAPK–NF-κB cascades in macrophages and synovial fibroblasts (PMID:21327328, PMID:22767598), directly ligates TLR4 via a protruding S402–N412 loop to activate NF-κB (PMID:26272519), signals through Ccr5 on muscle stem cells to drive proliferation (PMID:33568815), and fuels PARP1 hyperactivation and parthanatos in skin inflammation (PMID:34748530). NAMPT expression is transcriptionally controlled by STAT1 acting at the intronic NRE1 enhancer in response to IFN-γ (PMID:33976173) and by the circadian REV-ERB/E4BP4 axis (PMID:35036997), with NAMPT-dependent NAD+ in turn driving tissue-specific circadian metabolic oscillations (PMID:36996103); expression is also tuned post-transcriptionally by miR-146a targeting its 3'-UTR (PMID:35241643).

Mechanistic history

Synthesis pass · year-by-year structured walk · 10 steps
  1. 2006 High

    Establishing the enzyme class and catalytic architecture was the foundational question; the crystal structure defined NAMPT as a dimeric type II phosphoribosyltransferase and revealed how it synthesizes NMN from nicotinamide.

    Evidence X-ray crystallography with and without NMN product

    PMID:16783373

    Open questions at the time
    • Did not establish in vivo regulation of the enzyme
    • Allosteric and post-translational control sites not resolved
  2. 2007 High

    Whether NAMPT was rate-limiting for NAD+ biosynthesis and physiologically essential was unresolved; haplodeficiency and chemical inhibition causing NAD+ and insulin-secretion defects rescuable by NMN established its role as the rate-limiting salvage enzyme.

    Evidence Genetic haplodeficiency mouse, chemical inhibition, glucose-stimulated insulin secretion, NMN rescue, enzymatic assays

    PMID:16783373 PMID:17268245 PMID:17983582

    Open questions at the time
    • Tissue-specific contributions not dissected
    • Did not address extracellular function
  3. 2009 Medium

    Whether secreted NAMPT retained catalytic function was open; hepatocyte-secreted NAMPT was shown to be dimeric and enzymatically active, establishing an extracellular pool comparable to the intracellular form.

    Evidence Size exclusion chromatography and enzymatic assays on HepG2 and primary hepatocyte secretions

    PMID:19912992

    Open questions at the time
    • Secretion mechanism not defined
    • Physiological function of extracellular pool not addressed
  4. 2008 Medium

    Early functional studies asked whether NAMPT/PBEF acts in inflammation; reciprocal gain/loss-of-function linked it to IL-8 secretion, IL-1β-mediated permeability, and mitochondrial/oxidative-stress interactions in pulmonary cells.

    Evidence Overexpression and siRNA knockdown in A549/HPAEC, cytokine and permeability assays, Co-IP with ND1/ferritin/IFITM3

    PMID:18486613 PMID:18996492

    Open questions at the time
    • Interaction mechanism with mitochondrial partners unresolved
    • Enzymatic vs cytokine activity not separated
  5. 2013 High

    Whether the pro-inflammatory and pro-tumor actions of NAMPT require its catalytic activity was tested; pharmacological/genetic inhibition with NAD+/NMN rescue confirmed enzymatic dependence in myeloma growth, MAPK–NF-κB inflammation, and glucose-dependent islet secretion.

    Evidence APO866/FK866 inhibition, siRNA, NAD+/NMN rescue, PARP-1/SIRT-1 assays, xenografts, pathway inhibitors, secretion assays

    PMID:21327328 PMID:22767598 PMID:23435312 PMID:23536823

    Open questions at the time
    • Receptor mediating extracellular signaling not yet identified
    • Distinction between NMN production and direct ligand activity incomplete
  6. 2015 Medium

    The receptor for extracellular NAMPT cytokine activity was unknown; computational and functional analysis identified direct TLR4 ligation via an LPS-like S402–N412 loop driving NF-κB and lung injury.

    Evidence Computational structural analysis, TLR4/NF-κB reporter assays, VILI mouse model

    PMID:26272519

    Open questions at the time
    • Direct binding partly inferred computationally
    • Relationship between TLR4 ligation and enzymatic activity unresolved
  7. 2021 High

    How NAMPT couples to specific cellular outcomes was addressed across systems; macrophage-secreted NAMPT was found to signal through Ccr5 on muscle stem cells, IFN-γ/STAT1 to drive Nampt via the NRE1 enhancer for M1 macrophage glycolysis and anti-tumor immunity, REV-ERB/E4BP4 to set circadian Nampt expression, and NAMPT-derived NAD+ to fuel PARP1-driven parthanatos in skin.

    Evidence Zebrafish injury/live imaging, scRNAseq, ChIP-seq, NRE1 and Rev-erb KO mice, PARP1/NADPH-oxidase inhibition, human skin models

    PMID:33568815 PMID:33976173 PMID:34748530 PMID:35036997

    Open questions at the time
    • Ccr5 ligation mechanism distinct from enzymatic NAD+ not fully defined
    • How NAD+ flux selectively tunes specific effector genes incomplete
  8. 2022 High

    The post-transcriptional and post-translational control of NAMPT, and its downstream NAD+-dependent effector axes, were dissected; AMPK Ser314 phosphorylation enhances PRPP binding and DNA repair, miR-146a represses NAMPT via its 3'-UTR, lamin A/C and circRNA FEACR modulate NAMPT expression/stability, and myeloid NAMPT controls HIF-1α, efferocytosis, STING, and oxidative burst.

    Evidence In vitro kinase assay/S314 mutagenesis, luciferase 3'-UTR assay, ATAC-seq, RNA pull-down, myeloid-specific KO mice, scRNA-seq, NMN rescue, mitochondrial/SIRT1 assays

    PMID:31816398 PMID:35063804 PMID:35241643 PMID:36099415 PMID:36196536 PMID:37370086 PMID:38308188

    Open questions at the time
    • Mechanism linking NAD+ to HIF-1α stability not fully resolved
    • Integration of multiple regulatory inputs in vivo unclear
  9. 2023 Medium

    Allosteric activation and SIRT1 feedback regulation were defined; rear-channel positive allosteric modulators relieve NAM/NAD+ feedback inhibition, and SIRT1 binds and deacetylates NAMPT to raise its activity, while tissue-specific NAD+ control of the clock was mapped.

    Evidence SAR study with rear-channel binding assays, Co-IP, enzymatic assays, tissue-specific KO mice, transcriptomics/metabolomics

    PMID:36797299 PMID:36996103 PMID:38096366

    Open questions at the time
    • Structural basis of SIRT1-NAMPT interaction not solved
    • Why some tissues are refractory to NAMPT loss unexplained
  10. 2024 Medium

    NAMPT-controlled deacetylation of metabolic enzymes was added to the model, with the Nampt/SIRT2/LDHA axis shown to regulate lactate production.

    Evidence Co-IP for LDHA acetylation, FK866/SIRT2 inhibition, NMN supplementation, PCOS rat model

    PMID:39489197

    Open questions at the time
    • Direct vs NAD+-dependent regulation of SIRT2 not separated
    • Generality across cell types untested

Open questions

Synthesis pass · forward-looking unresolved questions
  • How the enzymatic (NAD+-generating) and non-enzymatic cytokine/receptor-ligand functions of extracellular NAMPT are mechanistically partitioned, and how a single secreted protein engages distinct receptors (TLR4, Ccr5) in different tissues, remains unresolved.
  • No structure of NAMPT bound to TLR4 or Ccr5
  • Secretion/export route of intracellular NAMPT undefined
  • Relative contribution of enzymatic vs ligand activity in vivo not quantified

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0016740 transferase activity 4 GO:0048018 receptor ligand activity 2 GO:0098772 molecular function regulator activity 1
Localization
GO:0005576 extracellular region 4 GO:0005829 cytosol 2 GO:0031410 cytoplasmic vesicle 1
Pathway
R-HSA-168256 Immune System 4 R-HSA-1430728 Metabolism 3 R-HSA-162582 Signal Transduction 3 R-HSA-9909396 Circadian clock 2 R-HSA-5357801 Programmed Cell Death 1 R-HSA-73894 DNA Repair 1
Partners
CCR5PARP1SIRT1TLR4

Evidence

Reading pass · 36 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
2006 Crystal structure of Nampt reveals it is a dimeric type II phosphoribosyltransferase; the structure in the presence and absence of NMN provides insights into the enzymatic mechanism of NMN synthesis from nicotinamide. X-ray crystallography (crystal structure determination with and without NMN product) Nature structural & molecular biology High 16783373
2007 Intracellular NAMPT (iNampt) is an essential NAD biosynthetic enzyme; haplodeficiency or chemical inhibition causes defects in NAD biosynthesis and glucose-stimulated insulin secretion in pancreatic islets, correctable by NMN supplementation. Extracellular NAMPT (eNampt) does not exert insulin-mimetic effects but exhibits robust NAD biosynthetic activity. Genetic haplodeficiency mouse model, chemical inhibition, in vitro and in vivo glucose-stimulated insulin secretion assays, NMN rescue experiments, plasma NMN measurement Cell metabolism High 17983582
2007 NAMPT is the rate-limiting enzyme that converts nicotinamide to nicotinamide mononucleotide (NMN) in the mammalian NAD biosynthetic salvage pathway from nicotinamide. Enzymatic activity assay, genetic and pharmacological perturbation of NAD biosynthesis Current opinion in gastroenterology High 16783373 17268245 17983582
2009 Human hepatocytes constitutively release NAMPT into the extracellular space in a time-dependent manner; secreted NAMPT is primarily dimeric and exhibits in vitro NAD biosynthetic enzymatic activity comparable to intracellular NAMPT. Size exclusion chromatography, enzymatic activity assay, cell culture secretion experiments with HepG2 and primary human hepatocytes Biochemical and biophysical research communications Medium 19912992
2008 NAMPT (PBEF) interacts with NADH dehydrogenase subunit 1 (ND1), ferritin light chain, and IFITM3 in human pulmonary vascular endothelial cells; PBEF overexpression increases these interactions and intracellular oxidative stress, attenuatable by rotenone. Protein interaction identification and validation (co-immunoprecipitation/pulldown), overexpression, rotenone inhibition, computational interaction modeling FEBS letters Medium 18486613
2008 NAMPT (PBEF) overexpression augments IL-8 secretion and IL-1β-mediated cell permeability in pulmonary vascular endothelial and epithelial cells; knockdown of PBEF inhibits IL-1β-stimulated IL-8 secretion and reduces cell permeability, establishing PBEF as a regulator of pulmonary inflammation and permeability. PBEF overexpression and siRNA knockdown in A549 and HPAEC cells, cytokine secretion assay, permeability assay Cell biology international Medium 18996492
2011 Extracellular NAMPT (visfatin) induces EMMPRIN and MMP-9 expression in macrophages via NAMPT enzymatic activity (NMN production) activating the MAPK (p38, ERK1/2)–NF-κB signaling pathway; this pro-inflammatory action is not prevented by insulin receptor blockade. Pharmacological inhibition (FK866, p38 inhibitor, ERK1/2 inhibitor, NF-κB inhibitor), exogenous NMN supplementation, RT-PCR, western blotting, gelatin zymography, THP-1 macrophage cell line International journal of molecular medicine Medium 21327328
2013 NAMPT (PBEF1) enzymatic activity is required for myeloma cell growth and osteoclast activity; inhibition by APO866 depletes NAD+, reduces PARP-1 and SIRT-1 activity, and induces apoptosis; effects are rescued by extracellular NAD+ or nicotinamide supplementation. PBEF1 knockdown phenocopies APO866 inhibition. APO866 pharmacological inhibition, PBEF1 siRNA knockdown, NAD+ rescue, PARP-1/SIRT-1 activity assays, SCID-rab in vivo xenograft model Experimental hematology High 23435312
2013 Human islets secrete enzymatically active eNAMPT in a glucose-dependent manner requiring membrane depolarization; glucose (20 mM) increases both eNAMPT secretion and NAMPT mRNA levels; secretion is attenuated by diazoxide and nifedipine (membrane depolarization inhibitors). Static glucose-stimulated insulin secretion assay, ELISA, enzymatic activity assay on secreted NAMPT, pharmacological inhibitors (diazoxide, nifedipine), qRT-PCR, immunofluorescence/confocal imaging PloS one Medium 23536823
2014 Visfatin/Nampt is present in human OA joint tissues in a homodimeric, enzymatically active conformation; inhibition of Nampt enzymatic activity by APO866 reduces pro-inflammatory cytokine (IL-6, KC, MCP-1) mRNA and protein expression in chondrocytes and osteoblasts, demonstrating that the pro-inflammatory action of visfatin requires its enzymatic (NAMPT) activity. Western blot, ELISA, size exclusion chromatography, colorimetric enzymatic activity assay, APO866 pharmacological inhibition, RT-PCR, primary murine chondrocyte and osteoblast cultures Arthritis research & therapy Medium 24479481
2015 Extracellular NAMPT/PBEF directly ligates Toll-like receptor 4 (TLR4) to induce NF-κB transcriptional activity and inflammatory lung injury; computational analysis shows NAMPT shares ~30% sequence identity and structural similarity with TLR4-binding protein MD-2; unlike MD-2, NAMPT alone produces robust TLR4 activation, likely via a protruding region (S402-N412) with structural similarity to LPS. Computational structural analysis, TLR4 signaling reporter assays, NF-κB transcriptional activity assays, VILI mouse model with reduced NAMPT bioavailability Scientific reports Medium 26272519
2012 Visfatin/PBEF induces high amounts of chemokines (IL-8, MCP-1), IL-6, and MMP-3 in rheumatoid arthritis synovial fibroblasts (RASFs) through p38 MAPK phosphorylation; p38 MAPK inhibition strongly reduces these effects; visfatin/PBEF also increases directed and general fibroblast motility. Affymetrix array, RT-PCR, immunoassay, p38 MAPK inhibitor, primary RASF cultures, migration assay The Journal of biological chemistry Medium 22767598
2012 NAMPT pathway controls GADD45A expression via FOXO3a acetylation: NAMPT overexpression decreases GADD45A expression while FK866 inhibition of NAMPT increases it; increased GADD45A expression under NAMPT inhibition involves FOXO3a acetylation (mediated through reduced SIRT1 activity). NAMPT overexpression, FK866 inhibition, SIRT1 shRNA knockdown, gene expression analysis Biochemical and biophysical research communications Medium 22430142
2021 Macrophage-derived NAMPT is required for muscle satellite cell (stem cell) proliferation after injury; specific 'dwelling' macrophages secrete NAMPT, which acts through the C-C motif chemokine receptor type 5 (Ccr5) expressed on muscle stem cells to stimulate proliferation. Zebrafish muscle injury models, live imaging of cell interactions, single-cell transcriptomics, genetic/pharmacological perturbation of NAMPT secretion Nature High 33568815
2021 STAT1 occupies a conserved enhancer element (NRE1) in intron 1 of Nampt in response to IFN-γ, driving Nampt expression; disruption of NRE1 reduces a subset of M1 macrophage genes sensitive to NAMPT activity through glycolytic processes; NRE1 deletion in macrophage lineages reduces anti-tumor immunity and increases tumor burden. ChIP-seq (STAT1 occupancy at NRE1), NRE1 mouse knockout strain, pharmacological NAMPT inhibition, scRNAseq, metabolic glycolysis assays Nature communications High 33976173
2021 NAMPT-derived NAD+ fuels PARP1 hyperactivation, which drives parthanatos cell death and skin inflammation; inhibition of NAMPT, PARP1, or NADPH oxidases reduces oxidative stress, keratinocyte DNA damage, and inflammation in zebrafish skin inflammation models; aberrant NAMPT and PARP activity, together with AIFM1 nuclear translocation, were observed in lesional psoriasis patient skin. Genetic and pharmacological inhibition (NAMPT, PARP1, NADPH oxidases), PAR glycohydrolase overexpression, zebrafish models, human organotypic 3D skin models, patient tissue analysis PLoS biology High 34748530
2021 REV-ERB nuclear receptors (REV-ERBα/β) in cardiomyocytes regulate NAMPT expression via repression of the transcription factor E4BP4; E4BP4 directly represses Nampt through distal cis-regulatory elements; REV-ERB-mediated E4BP4 repression is required for circadian Nampt expression and NAD+ salvage synthesis in heart. Cardiomyocyte-specific Rev-erb double knockout mice, cardiac phenotype analysis, ChIP (E4BP4 binding to Nampt regulatory elements), gene expression analysis Nature cardiovascular research High 35036997
2022 miR-146a directly targets the 3'-UTR of NAMPT mRNA to reduce NAMPT expression; AMPK activators (metformin, AICAR) suppress miR-146a expression at the transcriptional level by promoting IKK phosphorylation and attenuating NF-κB activity, thereby relieving repression of NAMPT and enabling NAD+/SIRT activation. Luciferase reporter assay (miR-146a targeting NAMPT 3'-UTR), miR-146a mimic/inhibitor transfection, AMPK activator treatment, IKK/NF-κB pathway analysis, in vitro and in vivo senescence models Signal transduction and targeted therapy High 35241643
2022 AMPK directly phosphorylates NAMPT at Ser314 in response to ionizing radiation within 30 minutes, increasing NAMPT enzymatic activity by enhancing NAMPT binding to its substrate PRPP; this phosphorylation restores NAD+ levels and facilitates DNA repair and cell viability. In vitro kinase assay, site-directed mutagenesis (S314 phosphorylation site), PRPP binding assays, NAD+ measurement, DNA repair assays in irradiated cells Open biology High 36196536
2022 NAMPT deletion in myeloid cells in colorectal cancer causes HIF-1α destabilization, reducing M2-like TAM polarization and decreasing efferocytosis; this decreased efferocytosis enhances STING signaling and type I IFN-response gene expression, potentiating cytotoxic T cell anti-tumor activity. Myeloid-specific Nampt conditional knockout mice, scRNA-seq, HIF-1α destabilization assay, efferocytosis assay, STING signaling assessment, T cell activity assays Advanced science High 38308188
2022 NAMPT promotes cell survival under oxidative stress via both SIRT1-dependent p53-CD38 pathway and a SIRT1-independent NRF2-PPARα/AMPKα pathway; NAMPT overexpression rescues mitochondrial membrane potential and content under H2O2 treatment via the NRF2-PPARα/AMPKα axis; NRF2 is identified as a downstream target of NAMPT. NAMPT overexpression, SIRT1 inhibition/knockdown, NRF2 pathway analysis, mitochondrial membrane potential assay, cell viability under oxidative stress Cellular signalling Medium 31816398
2022 NAMPT deletion in macrophages reduces phagocytic activity due to insufficient NAD+ needed to produce NADPH for the oxidative burst; NMN treatment rescues NADPH levels and restores superoxide generation via NADPH oxidase; NAMPT-deficient mice show impaired dead-cell clearance and prolonged chronic colitis. Myeloid-specific Nampt conditional knockout (Namptf/f LysMCre+/-), phagocytosis assay, NADPH/NAD+ measurement, NADPH oxidase activity, NMN rescue, DSS colitis model Redox biology High 35063804
2022 Lamin A/C null (Lmna-/-) MEFs show reduced NAMPT expression and attenuated SIRT1 activity; ATAC-seq reveals reduced chromatin accessibility at the Nampt gene promoter in Lmna-/- cells; this is associated with reduced NAD+ levels and mitochondrial dysfunction. Lmna-/- MEF and HGPS fibroblast models, ATAC-seq, NAD+ measurement, SIRT1 activity assay, PGC1α chromatin recruitment analysis Nucleic acids research Medium 36099415
2022 CircRNA FEACR directly binds NAMPT protein and enhances its protein stability, increasing NAMPT-dependent SIRT1 expression, which promotes FOXO1 transcriptional activity by reducing FOXO1 acetylation; FOXO1 upregulates FTH1 transcription to inhibit cardiomyocyte ferroptosis. RNA pull-down (FEACR binding to NAMPT), gain/loss-of-function experiments, western blotting, NAMPT stability assay, SIRT1/FOXO1/FTH1 pathway analysis Journal of biomedical science Medium 37370086
2022 NAMPT-containing microvesicles (MVs) shed by radioresistant glioma stem cells transfer NAMPT to radiosensitive cells; the enzymatic activity of NAMPT within recipient cells is necessary to increase intracellular NAD(H) levels and rescue proliferation of irradiated radiosensitive cells. Proteomic analysis of MVs, NAMPT-high MV transfer experiments, NAMPT enzymatic activity requirement assays, NAD(H) measurement in recipient cells, radioresistance phenotype assays Life science alliance Medium 37037593
2023 Low-dose nicotine restores age-related decline in NAMPT activity via SIRT1 binding to NAMPT followed by deacetylation of NAMPT, independent of nicotinic acetylcholine receptors; deacetylation of NAMPT by SIRT1 increases its enzymatic activity and NAD+ synthesis. Co-immunoprecipitation (SIRT1-NAMPT binding), NAMPT enzymatic activity assay, nicotinic receptor blockade, in vivo aging mouse model, 18F-FDG PET imaging Nature communications Medium 36797299
2023 NAMPT-dependent NAD+ control of the molecular clock varies substantially between tissues: brown adipose tissue (BAT) requires NAMPT for clock amplitude; skeletal muscle clock is refractory to NAMPT loss; NAMPT differentially orchestrates oscillation of clock-controlled gene networks and metabolites, including TCA cycle intermediates, in a tissue-specific manner. Tissue-specific Nampt knockout mouse models, transcriptomic analysis, metabolomics (TCA cycle intermediates), circadian amplitude measurements, cold challenge assay Proceedings of the National Academy of Sciences of the United States of America High 36996103
2024 NAMPT inhibition in macrophages causes HIF-1α destabilization, directly linking NAMPT-dependent NAD+ production to HIF-1α stability and M2-like macrophage polarization. Myeloid-specific Nampt KO, HIF-1α protein stability assay, macrophage polarization markers Advanced science (Weinheim, Baden-Wurttemberg, Germany) Medium 38308188
2023 Small molecule NAMPT positive allosteric modulators (N-PAMs) bind to the 'rear channel' of NAMPT, increasing enzyme activity and alleviating feedback inhibition by NAM and NAD+; binding affinity to the rear channel correlates directly with potency for enzyme activation, and activation translates to elevated cellular NAD+. Structure-activity relationship study (>70 compounds), rear channel binding affinity assays, enzymatic activity assays, cellular NAD+ measurement Journal of medicinal chemistry Medium 38096366
2024 NAMPT inhibition in macrophages reduces their efferocytosis activity due to insufficient NAD+-derived NADPH for oxidative burst; decreased efferocytosis activates STING signaling promoting type I IFN response genes. Myeloid-specific Nampt KO, efferocytosis assay, NADPH measurement, STING pathway assays, IFN-response gene expression Advanced science (Weinheim, Baden-Wurttemberg, Germany) Medium 38308188
2012 PBEF (NAMPT) induces VEGF secretion by amniotic epithelial cells and increases VEGFR2 expression in placental amniotic epithelial cells (but not reflected AEC); PBEF combined with VEGF increases permeability of the placental amnion, measured by DCF transfer across amnion explants. Primary human amniotic epithelial cell (AEC) cultures, VEGF ELISA, VEGFR2 expression analysis, amnion permeability assay with DCF tracer Placenta Medium 23151382
2015 NAMPT inhibits progesterone secretion in hen granulosa cells via its enzymatic (NAMPT) activity; recombinant NAMPT (100 ng/ml) reduces basal and IGF1-induced progesterone secretion and decreases STAR and HSD3B protein levels and MAPK3/1 phosphorylation; the effect is abolished by FK866, confirming enzymatic activity dependence. Primary hen granulosa cell cultures, FK866 enzymatic inhibition, progesterone ELISA, western blotting for STAR/HSD3B, MAPK3/1 phosphorylation assay Reproduction (Cambridge, England) Medium 25918435
2020 NAMPT inhibition in hypothalamic neurons by ICV-administered FK866 completely ablates fasting- and ghrelin-induced increases in food intake without causing malaise; NAMPT inhibition in primary hypothalamic neurons reduces NAD+, increases reactive oxygen species, affects mitochondrial respiration, and alters expression of Agrp and Pomc. ICV FK866 administration, metabolic cage food intake measurement, primary hypothalamic neuron FK866 treatment, ROS measurement, mitochondrial respiration assay, Agrp/Pomc gene expression Acta physiologica (Oxford, England) Medium 31900990
2022 NAMPT promotes IFNγ production by CD4+ T cells in lupus nephritis by supporting aerobic glycolysis and mitochondrial respiration through NAD+ production; NAMPT promotes translational efficiency of Ifng mRNA in CD4+ T cells; FK866 or siRNA knockdown suppresses IFNγ production and reduces kidney damage in lupus mice. NAMPT inhibition by FK866 and siRNA in CD4+ T cells from LN patients and MRL/lpr mice, glycolysis/mitochondrial respiration assay, translational efficiency assay, in vivo siRNA delivery with kidney damage scoring Molecular therapy Medium 36146932
2024 NAMPT inhibition by FK866 enhances acetylation of LDHA in cells, reducing LDHA activity and decreasing lactate production; NAMPT functions upstream of SIRT2 to regulate LDHA acetylation status, forming a Nampt/SIRT2/LDHA pathway that controls lactate production in granulosa cells. Co-immunoprecipitation (LDHA acetylation state), FK866 NAMPT inhibition, SIRT2 inhibition, NAMPT inhibitor and NMN supplementation in PCOS rat model Free radical biology & medicine Medium 39489197
2022 NAMPT depletion in hippocampal CA1 neurons causes mitochondrial swelling and decreased mitochondrial number, cognitive deficiency, and increased intracellular Aβ aggregation; in primary neurons, FK866 inhibition of NAMPT drops mitochondrial membrane potential and decreases neurite branching in a dose-dependent manner. Hippocampus-specific Nampt KO (rAAV-hSyn-Cre), transmission electron microscopy, immunofluorescence, FK866 inhibition in primary neurons, mitochondrial membrane potential assay Molecular neurobiology Medium 36441480

Source papers

Stage 0 corpus · 100 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
2007 Nampt/PBEF/Visfatin regulates insulin secretion in beta cells as a systemic NAD biosynthetic enzyme. Cell metabolism 766 17983582
2015 Physiological and pathophysiological roles of NAMPT and NAD metabolism. Nature reviews. Endocrinology 591 26215259
2008 Nampt: linking NAD biology, metabolism and cancer. Trends in endocrinology and metabolism: TEM 339 19109034
2007 The regulation of nicotinamide adenine dinucleotide biosynthesis by Nampt/PBEF/visfatin in mammals. Current opinion in gastroenterology 252 17268245
2006 Structure of Nampt/PBEF/visfatin, a mammalian NAD+ biosynthetic enzyme. Nature structural & molecular biology 246 16783373
2008 Pre-B cell colony-enhancing factor (PBEF)/visfatin: a novel mediator of innate immunity. Journal of leukocyte biology 232 18252866
2015 Inhibition of nicotinamide phosphoribosyltransferase (NAMPT) as a therapeutic strategy in cancer. Pharmacology & therapeutics 212 25709099
2009 Nicotinamide phosphoribosyltransferase (Nampt): a link between NAD biology, metabolism, and diseases. Current pharmaceutical design 198 19149599
2013 The importance of NAMPT/NAD/SIRT1 in the systemic regulation of metabolism and ageing. Diabetes, obesity & metabolism 187 24003918
2021 Macrophages provide a transient muscle stem cell niche via NAMPT secretion. Nature 182 33568815
2008 Role of adiponectin and PBEF/visfatin as regulators of inflammation: involvement in obesity-associated diseases. Clinical science (London, England : 1979) 172 18194136
2010 Nampt/PBEF/visfatin and cancer. Cancer biology & therapy 158 20647743
2015 Unique Toll-Like Receptor 4 Activation by NAMPT/PBEF Induces NFκB Signaling and Inflammatory Lung Injury. Scientific reports 155 26272519
2013 Visfatin/Nampt: an adipokine with cardiovascular impact. Mediators of inflammation 139 23843684
2020 Recent Advances in NAMPT Inhibitors: A Novel Immunotherapic Strategy. Frontiers in pharmacology 126 32477131
2016 Dual and Specific Inhibition of NAMPT and PAK4 By KPT-9274 Decreases Kidney Cancer Growth. Molecular cancer therapeutics 126 27390344
2013 Medicinal chemistry of nicotinamide phosphoribosyltransferase (NAMPT) inhibitors. Journal of medicinal chemistry 126 23679915
2009 Nicotinamide phosphoribosyltransferase (NAMPT/PBEF/visfatin) is constitutively released from human hepatocytes. Biochemical and biophysical research communications 120 19912992
2008 Visfatin/PBEF/Nampt: structure, regulation and potential function of a novel adipokine. Clinical science (London, England : 1979) 115 19016657
2023 Circular RNA FEACR inhibits ferroptosis and alleviates myocardial ischemia/reperfusion injury by interacting with NAMPT. Journal of biomedical science 101 37370086
2014 Expression and function of visfatin (Nampt), an adipokine-enzyme involved in inflammatory pathways of osteoarthritis. Arthritis research & therapy 89 24479481
2006 Nampt/PBEF/Visfatin: a regulator of mammalian health and longevity? Experimental gerontology 89 16842957
2018 NAMPT: A pleiotropic modulator of monocytes and macrophages. Pharmacological research 82 30031171
2022 Review of various NAMPT inhibitors for the treatment of cancer. Frontiers in pharmacology 81 36160449
2015 NAMPT as a Therapeutic Target against Stroke. Trends in pharmacological sciences 78 26538317
2022 miR-146a impedes the anti-aging effect of AMPK via NAMPT suppression and NAD+/SIRT inactivation. Signal transduction and targeted therapy 76 35241643
2013 Pre-B cell colony enhancing factor (PBEF), a cytokine with multiple physiological functions. Cytokine & growth factor reviews 71 23787158
2022 Astrocyte-derived exosomal nicotinamide phosphoribosyltransferase (Nampt) ameliorates ischemic stroke injury by targeting AMPK/mTOR signaling to induce autophagy. Cell death & disease 70 36539418
2011 Visfatin/PBEF/Nampt induces EMMPRIN and MMP-9 production in macrophages via the NAMPT-MAPK (p38, ERK1/2)-NF-κB signaling pathway. International journal of molecular medicine 70 21327328
2011 NAMPT in regulated NAD biosynthesis and its pivotal role in human metabolism. Current medicinal chemistry 67 21517777
2023 Nicotine rebalances NAD+ homeostasis and improves aging-related symptoms in male mice by enhancing NAMPT activity. Nature communications 63 36797299
2015 Nicotinamide phosphoribosyltransferase (NAMPT/PBEF/visfatin) is a tumoural cytokine released from melanoma. Pigment cell & melanoma research 63 26358657
2010 Visfatin/PBEF and atherosclerosis-related diseases. Current vascular pharmacology 60 19485930
2021 Circadian REV-ERBs repress E4bp4 to activate NAMPT-dependent NAD+ biosynthesis and sustain cardiac function. Nature cardiovascular research 59 35036997
2021 NAMPT-derived NAD+ fuels PARP1 to promote skin inflammation through parthanatos cell death. PLoS biology 58 34748530
2019 PPM1D mutations silence NAPRT gene expression and confer NAMPT inhibitor sensitivity in glioma. Nature communications 58 31439867
2006 Genetic variation in the visfatin gene (PBEF1) and its relation to glucose metabolism and fat-depot-specific messenger ribonucleic acid expression in humans. The Journal of clinical endocrinology and metabolism 56 16636125
2024 NAMPT-Driven M2 Polarization of Tumor-Associated Macrophages Leads to an Immunosuppressive Microenvironment in Colorectal Cancer. Advanced science (Weinheim, Baden-Wurttemberg, Germany) 55 38308188
2012 Visfatin/pre-B-cell colony-enhancing factor (PBEF), a proinflammatory and cell motility-changing factor in rheumatoid arthritis. The Journal of biological chemistry 55 22767598
2009 Overexpression of visfatin/PBEF/Nampt alters whole-body insulin sensitivity and lipid profile in rats. Annals of medicine 55 19263259
2016 Nicotinamide phosphoribosyltransferase (Nampt) in carcinogenesis: new clinical opportunities. Expert review of anticancer therapy 53 27186719
2009 A rare variant in the visfatin gene (NAMPT/PBEF1) is associated with protection from obesity. Obesity (Silver Spring, Md.) 50 19300429
2022 NAMPT: A critical driver and therapeutic target for cancer. The international journal of biochemistry & cell biology 49 35219878
2013 Nicotinamide phosphoribosyltransferase (NAMPT) inhibitors as therapeutics: rationales, controversies, clinical experience. Current drug targets 49 23531116
2008 Critical role of PBEF expression in pulmonary cell inflammation and permeability. Cell biology international 47 18996492
2021 A Stat1 bound enhancer promotes Nampt expression and function within tumor associated macrophages. Nature communications 46 33976173
2022 Lamin A/C impairments cause mitochondrial dysfunction by attenuating PGC1α and the NAMPT-NAD+ pathway. Nucleic acids research 45 36099415
2013 NAMPT/PBEF1 enzymatic activity is indispensable for myeloma cell growth and osteoclast activity. Experimental hematology 45 23435312
2011 Diurnal rhythm of circulating nicotinamide phosphoribosyltransferase (Nampt/visfatin/PBEF): impact of sleep loss and relation to glucose metabolism. The Journal of clinical endocrinology and metabolism 45 22090280
2015 Nampt/PBEF/visfatin exerts neuroprotective effects against ischemia/reperfusion injury via modulation of Bax/Bcl-2 ratio and prevention of caspase-3 activation. Journal of molecular neuroscience : MN 43 25603815
2012 Nampt/Visfatin/PBEF: a functionally multi-faceted protein with a pivotal role in malignant tumors. Current pharmaceutical design 43 22934941
2018 Down-regulation of NAMPT expression by mir-206 reduces cell survival of breast cancer cells. Gene 42 29886033
2013 Expression and regulation of nampt in human islets. PloS one 40 23536823
2022 circPTPN4 regulates myogenesis via the miR-499-3p/NAMPT axis. Journal of animal science and biotechnology 37 35152912
2022 Making Protein Degradation Visible: Discovery of Theranostic PROTACs for Detecting and Degrading NAMPT. Journal of medicinal chemistry 35 36442664
2019 NAMPT, GRN, and SERPINE1 signature as predictor of disease progression and survival in gliomas. Journal of cellular biochemistry 34 31710121
2015 Expression and effect of NAMPT (visfatin) on progesterone secretion in hen granulosa cells. Reproduction (Cambridge, England) 34 25918435
2011 Nampt and its potential role in inflammation and type 2 diabetes. Handbook of experimental pharmacology 32 21484571
2022 NAMPT mitigates colitis severity by supporting redox-sensitive activation of phagocytosis in inflammatory macrophages. Redox biology 31 35063804
2017 Inhibition of NAMPT decreases cell growth and enhances susceptibility to oxidative stress. Oncology reports 31 28714034
2015 Nampt/PBEF/visfatin upregulation in colorectal tumors, mirrored in normal tissue and whole blood of colorectal cancer patients, is associated with metastasis, hypoxia, IL1β, and anemia. BioMed research international 31 26075243
2012 Rapid and sensitive detection of Nampt (PBEF/visfatin) in human serum using an ssDNA aptamer-based capacitive biosensor. Biosensors & bioelectronics 30 22704839
2022 NAMPT is a metabolic checkpoint of IFNγ-producing CD4+ T cells in lupus nephritis. Molecular therapy : the journal of the American Society of Gene Therapy 29 36146932
2024 Photoswitchable PROTACs for Reversible and Spatiotemporal Regulation of NAMPT and NAD. Angewandte Chemie (International ed. in English) 28 38282119
2022 Addressing the Enzyme-independent tumor-promoting function of NAMPT via PROTAC-mediated degradation. Cell chemical biology 28 36323324
2019 NAMPT maintains mitochondria content via NRF2-PPARα/AMPKα pathway to promote cell survival under oxidative stress. Cellular signalling 28 31816398
2016 NAMPT and NAMPT-controlled NAD Metabolism in Vascular Repair. Journal of cardiovascular pharmacology 28 26485210
2023 NAMPT-dependent NAD+ biosynthesis controls circadian metabolism in a tissue-specific manner. Proceedings of the National Academy of Sciences of the United States of America 27 36996103
2015 The role of visfatin (PBEF/Nampt) in pregnancy complications. Journal of reproductive immunology 27 26451650
2008 Plasma levels of PBEF/Nampt/visfatin are decreased in patients with liver cirrhosis. American journal of physiology. Gastrointestinal and liver physiology 27 19074645
2020 Fasting- and ghrelin-induced food intake is regulated by NAMPT in the hypothalamus. Acta physiologica (Oxford, England) 26 31900990
2019 NAMPT overexpression alleviates alcohol-induced hepatic steatosis in mice. PloS one 26 30794635
2019 Targeting NAMPT as a therapeutic strategy against stroke. Stroke and vascular neurology 26 31338216
2012 Pre-B cell colony enhancing factor (PBEF/NAMPT/Visfatin) and vascular endothelial growth factor (VEGF) cooperate to increase the permeability of the human placental amnion. Placenta 26 23151382
2023 Recent advances of targeting nicotinamide phosphoribosyltransferase (NAMPT) for cancer drug discovery. European journal of medicinal chemistry 25 37413882
2020 Non-canonical roles of NAMPT and PARP in inflammation. Developmental and comparative immunology 25 33038343
2017 Discovery and Characterization of Novel Nonsubstrate and Substrate NAMPT Inhibitors. Molecular cancer therapeutics 25 28468779
2010 Visfatin/PBEF/Nampt: A New Cardiovascular Target? Frontiers in pharmacology 24 21833174
2023 Niacin restriction with NAMPT-inhibition is synthetic lethal to neuroendocrine carcinoma. Nature communications 23 38092728
2009 Lack of direct insulin-like action of visfatin/Nampt/PBEF1 in human adipocytes. Journal of physiology and biochemistry 22 20358348
2008 Interactions between PBEF and oxidative stress proteins--a potential new mechanism underlying PBEF in the pathogenesis of acute lung injury. FEBS letters 22 18486613
2007 Effects of genetic variation in the visfatin gene (PBEF1) on obesity, glucose metabolism, and blood pressure in children. Metabolism: clinical and experimental 22 17512309
2024 Drug discovery targeting nicotinamide phosphoribosyltransferase (NAMPT): Updated progress and perspectives. Bioorganic & medicinal chemistry 21 38244254
2024 Nampt/SIRT2/LDHA pathway-mediated lactate production regulates follicular dysplasia in polycystic ovary syndrome. Free radical biology & medicine 21 39489197
2007 Nampt/PBEF/Visfatin: a new player in beta cell physiology and in metabolic diseases? Cell metabolism 21 17983577
2024 The function of nicotinamide phosphoribosyl transferase (NAMPT) and its role in diseases. Frontiers in molecular biosciences 20 39513038
2022 Updated Functional Roles of NAMPT in Carcinogenesis and Therapeutic Niches. Cancers 20 35565188
2023 Transcriptome analysis reveals therapeutic potential of NAMPT in protecting against abdominal aortic aneurysm in human and mouse. Bioactive materials 19 38173843
2022 NAD/NAMPT and mTOR Pathways in Melanoma: Drivers of Drug Resistance and Prospective Therapeutic Targets. International journal of molecular sciences 19 36077374
2022 AMPK phosphorylates NAMPT to regulate NAD+ homeostasis under ionizing radiation. Open biology 19 36196536
2012 NAMPT pathway is involved in the FOXO3a-mediated regulation of GADD45A expression. Biochemical and biophysical research communications 19 22430142
2022 The Depletion of NAMPT Disturbs Mitochondrial Homeostasis and Causes Neuronal Degeneration in Mouse Hippocampus. Molecular neurobiology 18 36441480
2008 The visfatin (PBEF1) G-948T gene polymorphism is associated with increased high-density lipoprotein cholesterol in obese subjects. Metabolism: clinical and experimental 18 18940394
2021 Tripeptide IRW Upregulates NAMPT Protein Levels in Cells and Obese C57BL/6J Mice. Journal of agricultural and food chemistry 17 33522796
2013 Endogenous NAMPT dampens chemokine expression and apoptotic responses in stressed tubular cells. Biochimica et biophysica acta 17 24287278
2012 PBEF/NAMPT/visfatin: a promising drug target for treating rheumatoid arthritis? Future medicinal chemistry 17 22530639
2023 The NAMPT Inhibitor FK866 in Combination with Cisplatin Reduces Cholangiocarcinoma Cells Growth. Cells 16 36899911
2023 Proteomic analysis reveals microvesicles containing NAMPT as mediators of radioresistance in glioma. Life science alliance 16 37037593
2023 Synthesis, Optimization, and Structure-Activity Relationships of Nicotinamide Phosphoribosyltransferase (NAMPT) Positive Allosteric Modulators (N-PAMs). Journal of medicinal chemistry 15 38096366
2022 From Rate-Limiting Enzyme to Therapeutic Target: The Promise of NAMPT in Neurodegenerative Diseases. Frontiers in pharmacology 15 35903330

Missed literature

Know a paper Affinage missed for NAMPT? Flag it for the maintainers and the community.

No submissions yet.