ArticleCell research2022
Discovery of small-molecule activators of nicotinamide phosphoribosyltransferase (NAMPT) and their preclinical neuroprotective activity.
Article in Cell research, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 33 papers.
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Who cites it
33 citing papers in PubMed, 60 citations in OpenAlex.
- A Mechanism-Based Framework for Anti-Aging Strategies: From Metabolic Regulation to Senotherapy and Stem Cell-Based Interventions.Aging cell · 2026Review
- Nicotinamide Reverses the Warburg Effect in CHO Cell Culture.Biotechnology and bioengineering · 2026Article
- A novel NAMPT activator ameliorates obesity by repressing ACSL1-dependent lipid synthesis.Acta pharmaceutica Sinica. B · 2026Article
- Activation of the impaired NAMPT/SIRT7/SOD2 axis restores alveolar progenitor cell renewal in idiopathic pulmonary fibrosis.The Journal of clinical investigation · 2026Article
- FGF2 Enhances MSCs Secretome Therapy for Skin Photoaging by Delaying Senescence via iNAMPT/AMPK Signaling and Facilitating eNAMPT-Mediated Regenerative Crosstalk.Stem cell reviews and reports · 2026Article
- Preventing neuropathy and improving anticancer chemotherapy with a carbazole-based compound.Science advances · 2025Article
- Article
- The role of NADnpj metabolic health and disease · 2025Review
- Effects of quercetin and derivatives on NAMPT/Sirtuin-1 metabolic pathway in neuronal cells: an approach to mitigate chemotherapy-induced cognitive impairment.Metabolic brain disease · 2025Article
- Sonic hedgehog restrains the ubiquitin-dependent degradation of SP1 to inhibit neuronal/glial senescence associated phenotypes in chemotherapy-induced peripheral neuropathy via the TRIM25-CXCL13 axis.Journal of advanced research · 2025Article
- Alisol A ameliorates vascular cognitive impairment via AMPK/NAMPT/SIRT1-mediated regulation of cholesterol and autophagy.Theranostics · 2025Article
- Pathobiochemistry of Aging and Neurodegeneration: Deregulation of NAD+ Metabolism in Brain Cells.Biomolecules · 2024Review
- Targeted NADJournal of controlled release : official journal of the Controlled Release Society · 2024Article
- Excitatory neurons and oligodendrocyte precursor cells are vulnerable to focal cortical dysplasia type IIIa as suggested by single-nucleus multiomics.Clinical and translational medicine · 2024Article
- Molecular mechanisms of aging and anti-aging strategies.Cell communication and signaling : CCS · 2024Review
- Microbiota-derived 3-phenylpropionic acid promotes myotube hypertrophy by Foxo3/NADCell & bioscience · 2024Article
- Channeling Nicotinamide Phosphoribosyltransferase (NAMPT) to Address Life and Death.Journal of medicinal chemistry · 2024Review
- Macrophage senescence in health and diseases.Acta pharmaceutica Sinica. B · 2024Review
- Sirtuins in kidney diseases: potential mechanism and therapeutic targets.Cell communication and signaling : CCS · 2024Review
- Inhibitors of NADInternational journal of molecular sciences · 2024Review
Corrections and comments
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Authors and funding
21 authors at 5 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
The decline of nicotinamide adenine dinucleotide (NAD) occurs in a variety of human pathologies including neurodegeneration. NAD-boosting agents can provide neuroprotective benefits. Here, we report the discovery and development of a class of potent activators (NATs) of nicotinamide phosphoribosyltransferase (NAMPT), the rate-limiting enzyme in the NAD salvage pathway. We obtained the crystal structure of NAMPT in complex with the NAT, which defined the allosteric action of NAT near the enzyme active site. The optimization of NAT further revealed the critical role of K189 residue in boosting NAMPT activity. NATs effectively increased intracellular levels of NAD and induced subsequent metabolic and transcriptional reprogramming. Importantly, NATs exhibited strong neuroprotective efficacy in a mouse model of chemotherapy-induced peripheral neuropathy (CIPN) without any overt toxicity. These findings demonstrate the potential of NATs in the treatment of neurodegenerative diseases or conditions associated with NAD level decline.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.