ArticlePharmaceuticals (Basel, Switzerland)2022
Structure-Based Identification and Biological Characterization of New NAPRT Inhibitors.
Article in Pharmaceuticals (Basel, Switzerland), 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 12 papers.
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Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
12 citing papers in PubMed, 12 citations in OpenAlex.
- In silico studies on nicotinamide analogs as competitive inhibitors of nicotinamidase in methicillin-resistant Staphylococcus aureus.Molecular diversity · 2025Article
- The role of NADnpj metabolic health and disease · 2025Review
- Mechanisms of resistance to NAMPT inhibitors in cancer.Cancer drug resistance (Alhambra, Calif.) · 2025Review
- Biological Functions and Therapeutic Potential of NADCancers · 2024Review
- Inhibitors of NADInternational journal of molecular sciences · 2024Review
- Review
- Properly Substituted Benzimidazoles as a New Promising Class of Nicotinate Phosphoribosyltransferase (NAPRT) Modulators.Pharmaceuticals (Basel, Switzerland) · 2023Article
- A Versatile Continuous Fluorometric Enzymatic Assay for Targeting Nicotinate Phosphoribosyltransferase.Molecules (Basel, Switzerland) · 2023Article
- The Predictive Role of Extracellular NAPRT for the Detection of Advanced Fibrosis in Biopsy-Proven Non-Alcoholic Fatty Liver Disease.International journal of molecular sciences · 2023Article
- Targeting NADFrontiers in immunology · 2023Review
- NAMPT and NAPRT serum levels predict response to anti-TNF therapy in inflammatory bowel disease.Frontiers in medicine · 2023Article
- NAPRT, but Not NAMPT, Provides Additional Support for NAD Synthesis in Esophageal Precancerous Lesions.Nutrients · 2022Article
Corrections and comments
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Authors and funding
15 authors at 7 institutions in 4 countries.
Funding
Abstract
NAPRT, the rate-limiting enzyme of the Preiss-Handler NAD biosynthetic pathway, has emerged as a key biomarker for the clinical success of NAMPT inhibitors in cancer treatment. Previous studies found that high protein levels of NAPRT conferred resistance to NAMPT inhibition in several tumor types whereas the simultaneous blockade of NAMPT and NAPRT results in marked anti-tumor effects. While research has mainly focused on NAMPT inhibitors, the few available NAPRT inhibitors (NAPRTi) have a low affinity for the enzyme and have been scarcely characterized. In this work, a collection of diverse compounds was screened in silico against the NAPRT structure, and the selected hits were tested through cell-based assays in the NAPRT-proficient OVCAR-5 ovarian cell line and on the recombinant hNAPRT. We found different chemotypes that efficiently inhibit the enzyme in the micromolar range concentration and for which direct engagement with the target was verified by differential scanning fluorimetry. Of note, the therapeutic potential of these compounds was evidenced by a synergistic interaction between the NAMPT inhibitor FK866 and the new NAPRTi in terms of decreasing OVCAR-5 intracellular NAD levels and cell viability. For example, compound IM29 can potentiate the effect of FK866 of more than two-fold in reducing intracellular NAD levels. These results pave the way for the development of a new generation of human NAPRTi with anticancer activity.
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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.