ArticleBMC cancer2010
Target enzyme mutations are the molecular basis for resistance towards pharmacological inhibition of nicotinamide phosphoribosyltransferase.
Article in BMC cancer, 2010. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 27 papers.
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Who cites it
27 citing papers in PubMed.
- Mechanisms of resistance to NAMPT inhibitors in cancer.Cancer drug resistance (Alhambra, Calif.) · 2025Review
- Review
- The Kynurenine Pathway and Cancer: Why Keep It Simple When You Can Make It Complicated.Cancers · 2022Review
- Review of various NAMPT inhibitors for the treatment of cancer.Frontiers in pharmacology · 2022Review
- Inflammation-Related Gene Signature for Predicting the Prognosis of Head and Neck Squamous Cell Carcinoma.International journal of general medicine · 2022Article
- Evaluating Targeted Therapies in Ovarian Cancer Metabolism: Novel Role for PCSK9 and Second Generation mTOR Inhibitors.Cancers · 2021Article
- Structural Basis of Beneficial Design for Effective Nicotinamide Phosphoribosyltransferase Inhibitors.Molecules (Basel, Switzerland) · 2020Article
- Cross resistance to diverse anticancer nicotinamide phosphoribosyltransferase inhibitors induced by FK866 treatment.Oncotarget · 2018Article
- Targeting the vulnerability to NADLeukemia · 2018Article
- Cancer cell metabolic plasticity allows resistance to NAMPT inhibition but invariably induces dependence on LDHA.Cancer & metabolism · 2018Article
- Inhibition of nicotinamide phosphoribosyltransferase and depletion of nicotinamide adenine dinucleotide contribute to arsenic trioxide suppression of oral squamous cell carcinoma.Toxicology and applied pharmacology · 2017Article
- Extracellular nicotinamide phosphoribosyltransferase, a new cancer metabokine.British journal of pharmacology · 2016Review
- Extensive regulation of nicotinate phosphoribosyltransferase (NAPRT) expression in human tissues and tumors.Oncotarget · 2016Article
- New strategies to maximize therapeutic opportunities for NAMPT inhibitors in oncology.Molecular & cellular oncology · 2016Review
- Physiological and pathophysiological roles of NAMPT and NAD metabolism.Nature reviews. Endocrinology · 2015Review
- Discovery and characterization of novel small-molecule inhibitors targeting nicotinamide phosphoribosyltransferase.Scientific reports · 2015Article
- The Role of Nicotinamide Phosphoribosyltransferase in Cerebral Ischemia.Current topics in medicinal chemistry · 2015Review
- NAMPT is the cellular target of STF-31-like small-molecule probes.ACS chemical biology · 2014Article
- Oligo-carrageenan kappa-induced reducing redox status and activation of TRR/TRX system increase the level of indole-3-acetic acid, gibberellin A3 and trans-zeatin in Eucalyptus globulus trees.Molecules (Basel, Switzerland) · 2014Article
- Oligo-carrageenan kappa-induced reducing redox status and increase in TRR/TRX activities promote activation and reprogramming of terpenoid metabolism in Eucalyptus trees.Molecules (Basel, Switzerland) · 2014Article
Corrections and comments
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Authors and funding
13 authors.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundInhibitors of nicotinamide phosphoribosyltransferase (NAMPT) are promising cancer drugs currently in clinical trials in oncology, including APO866, CHS-828 and the CHS-828 prodrug EB1627/GMX1777, but cancer cell resistance to these drugs has not been studied in detail.
methodsHere, we introduce an analogue of CHS-828 called TP201565 with increased potency in cellular assays. Further, we describe and characterize a panel of cell lines with acquired stable resistance towards several NAMPT inhibitors of 18 to 20,000 fold compared to their parental cell lines.
resultsWe find that 4 out of 5 of the resistant sublines display mutations of NAMPT located in the vicinity of the active site or in the dimer interface of NAMPT. Furthermore, we show that these mutations are responsible for the resistance observed. All the resistant cell lines formed xenograft tumours in vivo. Also, we confirm CHS-828 and TP201565 as competitive inhibitors of NAMPT through docking studies and by NAMPT precipitation from cellular lysate by an analogue of TP201565 linked to sepharose. The NAMPT precipitation could be inhibited by addition of APO866.
conclusionWe found that CHS-828 and TP201565 are competitive inhibitors of NAMPT and that acquired resistance towards NAMPT inhibitors can be expected primarily to be caused by mutations in NAMPT.
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