The DOI matches its Crossref record; 42 of the 42 references it cites were found in a registry or an index.
The Small Molecule GMX1778 Is a Potent Inhibitor of NAD + Biosynthesis: Strategy for Enhanced Therapy in Nicotinic Acid Phosphoribosyltransferase 1-Deficient Tumors
Open accessAbstract
GMX1777 is a prodrug of the small molecule GMX1778, currently in phase I clinical trials for the treatment of cancer. We describe findings indicating that GMX1778 is a potent and specific inhibitor of the NAD(+) biosynthesis enzyme nicotinamide phosphoribosyltransferase (NAMPT). Cancer cells have a very high rate of NAD(+) turnover, which makes NAD(+) modulation an attractive target for anticancer therapy. Selective inhibition by GMX1778 of NAMPT blocks the production of NAD(+) and results in tumor cell death. Furthermore, GMX1778 is phosphoribosylated by NAMPT, which increases its cellular retention. The cytotoxicity of GMX1778 can be bypassed with exogenous nicotinic acid (NA), which permits NAD(+) repletion via NA phosphoribosyltransferase 1 (NAPRT1). The cytotoxicity of GMX1778 in cells with NAPRT1 deficiency, however, cannot be rescued by NA. Analyses of NAPRT1 mRNA and protein levels in cell lines and primary tumor tissue indicate that high frequencies of glioblastomas, neuroblastomas, and sarcomas are deficient in NAPRT1 and not susceptible to rescue with NA. As a result, the therapeutic index of GMX1777 can be widended in the treatment animals bearing NAPRT1-deficient tumors by coadministration with NA. This provides the rationale for a novel therapeutic approach for the use of GMX1777 in the treatment of human cancers.
Overview
Integrity signals
Registry
Cites
Statistics
Verification
Claims the paper makes
Claims other papers make about this one
Each is checked against this paper’s own text: does it say what the citing paper says it does?
In the citing paper
“Small-molecules targeting NAMPT can be effective anti-tumor agents in vitro and in xenograft cancer models (Nahimana et al., 2009; Tan et al., 2015b; Watson et al., 2009).”
From Targeting Metabolism for Cancer Therapy (2017) · cites this paper as Watson et al., 2009
Citations
Cites
1 retracted
Fukuhara, A., Matsuda, M., Nishizawa, M., Segawa, K., Tanaka, M., Kishimoto, K., Matsuki, Y., Murakami, M., Ichisaka, T., Murakami, H., et al. (2007) · Science · doi:10.1126/science.318.5850.565b · Cited by 150
RetractedPoly(ADP-ribose): novel functions for an old molecule
Schreiber, V., Dantzer, F., Amé, J., & de MURCIA, G. (2006) · Nature Reviews Molecular Cell Biology · doi:10.1038/nrm1963 · Cited by 1,975
Lin, S.-J., Defossez, P.-A., & Guarente, L. (2000) · Science · doi:10.1126/science.289.5487.2126 · Cited by 1,775
The Sir2 Family of Protein Deacetylases
Blander, G., & Guarente, L. (2004) · Annual Review of Biochemistry · doi:10.1146/annurev.biochem.73.011303.073651 · Cited by 1,497
A gene expression database for the molecular pharmacology of cancer
Scherf, U., Ross, D. T., Waltham, M. C., Smith, L. H., Lee, J. K., Tanabe, L. K., Kohn, K. W., Reinhold, W. C., Myers, T. G., Andrews, D. T., et al. (2000) · Nature Genetics · doi:10.1038/73439 · Cited by 1,450
Cloning and Characterization of the cDNA Encoding a Novel Human pre-B-Cell Colony-enhancing Factor
Samal, B. B., Sun, Y., Stearns, G., Xie, C., Suggs, S. V., & McNiece, I. (1994) · Molecular and Cellular Biology · doi:10.1128/mcb.14.2.1431 · Cited by 1,025
Revollo, J. R., Grimm, A. A., & Imai, S.-I. (2004) · Journal of Biological Chemistry · doi:10.1074/jbc.m408388200 · Cited by 1,010
Nampt/PBEF/Visfatin Regulates Insulin Secretion in β Cells as a Systemic NAD Biosynthetic Enzyme
Revollo, J. R., Körner, A., Mills, K. F., Satoh, A., Wang, T., Garten, A., Dasgupta, B., Sasaki, Y., Wolberger, C., Townsend, R. R., et al. (2007) · Cell Metabolism · doi:10.1016/j.cmet.2007.09.003 · Cited by 911
The power to reduce: pyridine nucleotides—small molecules with a multitude of functions
Pollak, N., Dölle, C., & Ziegler, M. (2007) · Biochemical Journal · doi:10.1042/bj20061638 · Cited by 730
Nuclear ADP-Ribosylation Reactions in Mammalian Cells: Where Are We Today and Where Are We Going?
Hassa, P. O., Haenni, S. S., Elser, M., & Hottiger, M. O. (2006) · Microbiology and Molecular Biology Reviews · doi:10.1128/mmbr.00040-05 · Cited by 719
Flagged first, then by citations
Research works printed but not linked: 1
- 10.1128/mcb.14.2.1431-1437.1994 · DOI
Cited by
Sorted by citations
Items 201–249 of 249
Dual Roles of Nicotinamide Phosphoribosyltransferase as a Promising Target for Cancer Radiotherapy
Xiang, B., Wang, X. Y., & Liu, K. J. (2021) · Radiation Research · doi:10.1667/rade-20-00273.1 · Cited by 2
Kim, A., Bhardwaj, P., Heer, C. D., Zhao, S. J., Lucas, K. N., Noronha, K. J., Friedman, S., Morotti, R., Sundaram, R. K., Rehman, S., et al. (2026) · Molecular Cancer Therapeutics · doi:10.1158/1535-7163.mct-25-0619 · Cited by 2
Efficacy of NAMPT inhibition in T-cell acute lymphoblastic leukemia
Vrana, C., Zhang, M., Rochette, M. P., Alozie, M. C., Oviedo, H. H., Gonzalez, A., Sherman, J., Zorman, B., Sumazin, P., Rabin, K. R., et al. (2025) · PLoS ONE · doi:10.1371/journal.pone.0324443 · Cited by 1
The role of chemerin, elafin, and visfatin in the pathogenesis of atopic dermatitis
Matwiejuk, M., Kulczyńska‐Przybik, A., Myśliwiec, H., Mikłosz, A., Chabowski, A., Mroczko, B., & Flisiak, I. (2025) · Frontiers in Immunology · doi:10.3389/fimmu.2025.1628163 · Cited by 1
NAMPT beyond NAD+ biosynthesis: roles in tumor microenvironment remodeling and cancer progression
Sun, W.-D., Bi, S.-Z., Zhu, X., Lai, S.-Y., Zhang, C., Liu, A., & Li, J.-H. (2026) · Biochemical Pharmacology · doi:10.1016/j.bcp.2026.118344 · Cited by 2
Bakr, H., Al-Awar, A., Spetz, J. K. E., & Forssell-Aronsson, E. B. (2026) · International Journal of Molecular Sciences · doi:10.3390/ijms27198709 · Cited by 1
In silico screening of candidate NAMPT modulators for treatment of age-related diseases
Nahálková, J., & Zanchi, F. B. (2026) · In Silico Research in Biomedicine · doi:10.1016/j.insi.2026.100587 · Cited by 1
From anti-aging drugs to cancer therapy: is there a potential for sirtuin activators in gliomas?
Opitz, C. A., & Turcan, Ş. (2020) · Neuro-Oncology · doi:10.1093/neuonc/noaa234 · Cited by 1
Biomarkers and Metabolomics, Evidence of Stress
Keum, Y. S., Kim, J., & Li, Q. X. (2012) · Springer eBooks · doi:10.1007/978-1-4614-5764-0_4
Aspects on Diagnosis and Treatment of Gastrointestinal Neuroendocrine Tumours
Swärd, C. (2010) · Gothenburg University Publications Electronic Archive (Gothenburg University)
Haverty, P. M., Liederer, B. M., Liang, X., Yauch, R. L., O’Brien, T., Bourgon, R., Koeppen, H., & Belmont, L. D. (2013)
Metadata of the chapter that will be visualized in SpringerLink
Fass, D. (2017) · Zhytomyr State University Library (Zhytomyr Ivan Franko State University)
Biomarkers and Metabolomics, Evidence of Stress
Keum, Y. S., Kim, J., & Li, Q. X. (2012) · Springer eBooks · doi:10.1007/978-1-4419-0851-3_41
Nicotinamide Phosphoribosyl Transferase and Cancer: A Molecular Nutrition Link
Zhang, L. Q., Heruth, D. P., Lee, M. W., Li, D., Maulik, D., & Ye, S. Q. (2016) · journal of nutritional oncology · doi:10.34175/jno201601005
Jiangzhou, S. O. N. G., Zou, G., Hao, H., Ya, Z. H. U., Jiayu, X. U. E., Ao, L., Sun, H., Hao, H., ZHANG, B., & Xu, X. (2024) · Chinese Journal of Natural Medicines · doi:10.1016/s1875-5364(24)60564-9
Shomali, M., Hilairet, S., Duhamel, M., Nardi, F., Bertrand, T., Mathieu, M., Arrebola, R., Pénarier, G., Jegham, S., Arigon, J., et al. (2024) · bioRxiv (Cold Spring Harbor Laboratory) · doi:10.1101/2024.12.11.628028
In silico screening of candidate NAMPT modulators for treatment of age-related diseasesPreprint
Nahálková, J., & Zanchi, F. B. (2025) · bioRxiv (Cold Spring Harbor Laboratory) · doi:10.1101/2025.04.07.647561
NAD+ as a Target for Cancer Treatment
Helman, T. J., & Braidy, N. (2025) · Springer eBooks · doi:10.1007/978-3-032-00771-1_269
Peng, H., Zhu, L., shen, L., Li, Z., Shi, Y., Ding, R., Zhang, T., Hu, C., He, J., Wang, Z., et al. (2026) · European Journal of Medicinal Chemistry · doi:10.1016/j.ejmech.2026.118699
Pyrimidine and NAD salvage pathways : unexpected allies in the maintenance of genome stability
Silveira, S. C. (2018) · theses.fr (ABES) · doi:10.70675/d8951764z7ae2z4d5eza2e1z0b24bea9f901
Ruedas, P., Gruß, H., Hempelmann, A., Vranic, M., Neuberth, S., Petrich, V., Gross, D., Pálfí, A., Pahl, A. M., & Hechler, T. (2026) · ACS Bio & Med Chem Au · doi:10.1021/acsbiomedchemau.6c00047
BindingDB (2020) · UC San Diego · doi:10.7270/q2cz39ph
BindingDB (2024) · UC San Diego · doi:10.7270/q26t0rwh
BindingDB (2011) · UC San Diego · doi:10.7270/q2vt1qjw
BindingDB (2025) · UC San Diego · doi:10.7270/q25x2fk7
BindingDB (2011) · UC San Diego · doi:10.7270/q2sn096q
BindingDB Entry 50020252: Discovery of potent NAMPT-Targeting PROTACs using FK866 as the warhead.
BindingDB (2024) · UC San Diego · doi:10.7270/q2f19459
BindingDB (2014) · UC San Diego · doi:10.7270/q25q4xj8
Metadata
- Authors
- Watson, M., Roulston, A., Bélec, L., Billot, X., Marcellus, R., Bédard, D., Bernier, C., Branchaud, S., Chan, H., Dairi, K., Gilbert, K., Goulet, D., Gratton, M.-O., Isakau, H., Jang, A., Khadir, A., Koch, E., Lavoie, M., Lawless, M., Nguyen, M., Paquette, D., Turcotte, E., Berger, A., Mitchell, M., Shore, G. C., & Beauparlant, P.
- Affiliations
- Inimex Pharmaceuticals (Canada) (CA)
- Gemin X Pharmaceuticals Canada Inc., Montréal
- McGill University (CA)
- Metabolon (United States) (US)
- Corresponding author
- Watson, Mark
- ORCID
- Venue
- Molecular and Cellular Biology
- Publisher
- Informa UK Limited
- Published
- 2009-11
- Volume
- 29
- Issue
- 21
- Pages
- 5872-5888
- ISSN
- 0270-7306 (ISSN-L)
- 1098-5549
- PMC
- PMC2772749
- OpenAlex
- W2119700304
- Cited by
- 229
- References
- 42
- Citations by year
- 2026: 10 · 2025: 10 · 2024: 14 · 2023: 10 · 2022: 15 · 2021: 14 · 2020: 13 · 2019: 16 · 2018: 11 · 2017: 18 · 2016: 12 · 2015: 14 · 2014: 16 · 2013: 21 · 2012: 17
- FWCI
- 8.53
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Molecular and Cellular Biology (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Topics
- Health Sciences › Medicine › Geriatrics and Gerontology › Sirtuins and Resveratrol in Medicine
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Biochemical and Molecular Research
- Health Sciences › Medicine › Oncology › PARP inhibition in cancer therapy
- Keywords
- visfatin, nicotinic acid, prodrugs, cancer cell death, glioblastoma, neuroblastoma, sarcoma, cancer therapy
- MeSH terms
- Animals, Cyanides, Guanidines, Humans, Models, Biological, Models, Molecular, NAD, Neoplasms, Niacin, Phosphorylation, Ribose, Substrate Specificity, Gene Expression Regulation, Enzymologic, Gene Expression Regulation, Neoplastic, Cell Death, Drug Resistance, Neoplasm, Xenograft Model Antitumor Assays, Cell Line, Tumor, Mice, Nicotinamide Phosphoribosyltransferase
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
Are you an author, or do you see a problem with this page? Request a review
