Inhibition of nicotinamide phosphoribosyltransferase (NAMPT) as a therapeutic strategy in cancer

Sampath, Deepak; Zabka, Tanja S.; Misner, Dinah; O’Brien, Thomas G.; Dragovich, Peter S.

doi:10.1016/j.pharmthera.2015.02.004

Cited by 225 publications

(226 citation statements)

References 91 publications

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“…In addition, NAD + , as a product of NAM metabolism, is regulated by an enzymatic reaction by NAMPT. Inhibitors of the NAMPT, such as FK866 and other small molecules, are currently under clinical trial to evaluate an effect on metabolic perturbations in various cancers (78,79).…”

Section: Discussionmentioning

confidence: 99%

Nicotinamide metabolism regulates glioblastoma stem cell maintenance

Jung¹,

Kim²,

Wang³

et al. 2017

JCI Insight

109

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Section: Discussionmentioning

confidence: 99%

Nicotinamide metabolism regulates glioblastoma stem cell maintenance

Jung¹,

Kim²,

Wang³

et al. 2017

JCI Insight

109

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“…Unique among malignancies, high levels of eNAMPT in MPN-associated myelofibrosis predicted a restraint of the disease progression toward a more severe disease phenotype and leukemia. As a key regulator of NAD1 biosynthesis, NAMPT is deemed to be a potential cancer therapeutic target [47][48][49][50]. In MPN-associated myelofibrosis a full exploitation of the relevance of anti-NAMPT therapy needs a full understanding of the complex relation between inflammation, NAMPT, myeloproliferation, and disease progression.…”

Section: Discussionmentioning

confidence: 99%

Increased plasma nicotinamide phosphoribosyltransferase is associated with a hyperproliferative phenotype and restrains disease progression in MPN‐associated myelofibrosis

et al. 2016

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Myeloproliferative neoplasm (MPN)-associated myelofibrosis is a clonal, neoplastic disorder of the hematopoietic stem cells, in which inflammation and immune dysregulation play an important role. Extracellular nicotinamide phosphoribosyltransferase (eNAMPT), also known as visfatin, is a cytokine implicated in a number of inflammatory and neoplastic diseases. Here plasma levels of eNAMPT in patients with MPN-associated myelofibrosis and their effects on disease phenotype and outcomes were examined. The concordance of eNAMPT levels with the marker of general inflammation high-sensitivity C-reactive protein (hs-CRP) was also studied. A total of 333 MPN-associated myelofibrosis patients (187 males and 146 females) and 31 age-and gender-matched normal-weight healthy subjects were enrolled in the study main body. Levels of eNAMPT and hs-CRP were simultaneously assayed in 209 MPN-associated myelofibrosis patients. Twenty-four polycythemia vera or essential thrombocythemia patients were used as controls. eNAMPT was over expressed in MPN-associated myelofibrosis, and eNAMPT expression was correlated with higher white blood cell count, higher hemoglobin, and higher platelet count, suggesting that eNAMPT is an indispensable permissive agent for myeloproliferation of MPN-associated myelofibrosis. The lack of correlation between eNAMPT and hs-CRP revealed that eNAMPT in MPN-associated myelofibrosis does not behave as a canonical inflammatory cytokine. In addition, higher levels of eNAMPT predicted longer time to blast transformation, and protected against progression toward thrombocytopenia and large splenomegaly. In conclusion, in MPN-associated myelofibrosis high levels of eNAMPT mark the myeloproliferative potential and, at variance with a high number of cancers, are protective against disease progression.Am. J.

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“…As a result, NAD ϩ biosynthetic processes, which promote activity of NAD ϩ consumers, have been examined as drug targets (3)(4)(5). There is interest in both boosting NAD ϩ biosynthesis for therapeutic benefit in age-related diseases (6) and inhibiting NAD ϩ biosynthesis for therapeutic benefit in cancer (7)(8)(9). However, we have not fully elucidated how perturbing the availability of specific NAD ϩ biosynthetic precursors or the availability of NAD ϩ in various tissues or cellular compartments impacts organism physiology, especially beyond the activity of the NAD ϩ consumers.…”

mentioning

confidence: 99%

“…For example, although we have largely eradicated pellagra, the deadly disease resulting from dietary deficiency of vitamin B 3 , via supplementation of our food supply, we still lack a basic understanding of the etiology of the hallmark skin, digestive, and nervous system pathologies that are presumably due, at least in part, to a deficiency in NAD ϩ biosynthesis (10,11). Furthermore, the mechanisms leading to toxicity upon treatment with inhibitors of NAD ϩ salvage biosynthesis are not well elucidated (9), and effects on development are largely unexamined.…”

mentioning

confidence: 99%