A fluorometric assay for high-throughput screening targeting nicotinamide phosphoribosyltransferase

Zhang, Ruoyu; Ye, Qin; Lv, Xiaoqun; Wang, Pei; Xu, Tao; Zhang, Lei; Miao, Chao‐Yu

doi:10.1016/j.ab.2010.12.035

Cited by 53 publications

(63 citation statements)

References 45 publications

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“…[94][95][96] Approximately, 348 compounds with NAMPT activity ,40% and 495 compounds with NAMPT activity .125% at the concentration of 20 mM have been obtained. [94][95][96] Although we have discovered several structurally diverse NAMPT inhibitors with potential to be anticancer agents, 97 the hits of NAMPT activators are still under verification in our laboratory. P7C3 neuroprotective chemicals are a group of compounds with potential to raise NAD concentration through activating of NAMPT.…”

Section: Nampt Activatormentioning

confidence: 99%

NAMPT and NAMPT-controlled NAD Metabolism in Vascular Repair

Wang

Liu

et al. 2016

Journal of Cardiovascular Pharmacology

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Vascular repair plays important roles in postischemic remodeling and rehabilitation in cardiovascular and cerebrovascular disease, such as stroke and myocardial infarction. Nicotinamide adenine dinucleotide (NAD), a well-known coenzyme involved in electron transport chain for generation of adenosine triphosphate, has emerged as an important controller regulating various biological signaling pathways. Nicotinamide phosphoribosyltransferase (NAMPT) is the rate-limiting enzyme for NAD biosynthesis in mammals. NAMPT may also act in a nonenzymatic manner, presumably mediated by unknown receptor(s). Rapidly accumulating data in the past decade show that NAMPT and NAMPT-controlled NAD metabolism regulate fundamental biological functions in endothelial cells, vascular smooth muscle cells, and endothelial progenitor cells. The NAD-consuming proteins, including sirtuins, poly-ADP-ribose polymerases (PARPs), and CD38, may contribute to the regulatory effects of NAMPT-NAD axis in these cells and vascular repair. This review discusses the current data regarding NAMPT and NAMPT-controlled NAD metabolism in vascular repair and the clinical potential translational application of NAMPT-related products in treatment of cardiovascular and cerebrovascular disease.

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Section: Nampt Activatormentioning

confidence: 99%

NAMPT and NAMPT-controlled NAD Metabolism in Vascular Repair

Wang

Liu

et al. 2016

Journal of Cardiovascular Pharmacology

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“…In previous studies, NMN was administered to mice at doses of~1 00 mg·kg À1 (Park et al, 2016) to 500 mg·kg À1 (Long et al, 2015;Uddin et al, 2016). However, most studies applied the dose of 300 mg·kg À1 Yoshino et al, 2011;Zhang et al, 2011;Stein and Imai, 2014;Zhao et al, 2015b;de Picciotto et al, 2016;Wei et al, 2017); therefore, we used 300 mg·kg À1 in this study.…”

Section: Delayed Tpa Treatment and Nmn Administrationmentioning

confidence: 99%

NAD replenishment with nicotinamide mononucleotide protects blood–brain barrier integrity and attenuates delayed tissue plasminogen activator‐induced haemorrhagic transformation after cerebral ischaemia

Wei

Kong

Xia

et al. 2017

British J Pharmacology

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Tissue plasminogen activator (tPA) is the only approved pharmacological therapy for acute brain ischaemia; however, a major limitation of tPA is the haemorrhagic transformation that follows tPA treatment. Here, we determined whether nicotinamide mononucleotide (NMN), a key intermediate of nicotinamide adenine dinucleotide biosynthesis, affects tPA-induced haemorrhagic transformation. EXPERIMENTAL APPROACHMiddle cerebral artery occlusion (MCAO) was achieved in CD1 mice by introducing a filament to the left MCA for 5 h. When the filament was removed for reperfusion, tPA was infused via the tail vein. A single dose of NMN was injected i.p. (300 mg·kg À1 ). Mice were killed at 24 h post ischaemia, and their brains were evaluated for brain infarction, oedema, haemoglobin content, apoptosis, neuroinflammation, blood-brain barrier (BBB) permeability, the expression of tight junction proteins (TJPs) and the activity/expression of MMPs. KEY RESULTSIn the mice infused with tPA at 5 h post ischaemia, there were significant increases in mortality, brain infarction, brain oedema, brain haemoglobin level, neural apoptosis, Iba-1 staining (microglia activation) and myeloperoxidase staining (neutrophil infiltration). All these tPA-induced alterations were significantly prevented by NMN administration. Mechanistically, the delayed tPA treatment increased BBB permeability by down-regulating TJPs, including claudin-1, occludin and zonula occludens-1, and enhancing the activities and protein expression of MMP9 and MMP2. Similarly, NMN administration partly blocked these tPA-induced molecular changes. CONCLUSIONS AND IMPLICATIONSOur results demonstrate that NMN ameliorates tPA-induced haemorrhagic transformation in brain ischaemia by maintaining the integrity of the BBB.

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“…Preclinical [125] Compound 7 (E)-N-(4-(1-benzoylpeperidin-4-yl) butyl)-3-(1H-pyrrol-2-yl)acrylamide [117] None Unknown Newly identified [117] Jin Song biflavone 17.5 µM [117] None Unknown Newly identified [117] Amentotaxus biflavone ND [117] None Unknown Newly identified [117] IUPAC: International Union of Pure and Applied Chemistry; ND: Not disclosed.…”

Section: N´-4-pyridylguanidine)mentioning

confidence: 99%

“…More recently, a high-throughput screening strategy has been developed to discover novel NAMPT inhibitors [117]; NAMPT activity can be detected fluorometrically by the conversion of its enzymatic product NMN to a fluorescent derivative through a sequential reaction with acetophenone/KOH and formic acid. Using this approach, a large panel of compounds can be screened for their ability to inhibit this reaction.…”

Section: Future Perspectivementioning

confidence: 99%

“…Using this approach, a large panel of compounds can be screened for their ability to inhibit this reaction. This sensitive screening approach may assist in the discovery of new potential NAMPT inhibitors [117]. Interestingly, screening using this approach has revealed inhibitory effects of NAMPT activity by three naturally occurring compounds, namely gallotanine, Jin Song biflavone and amentotaxus biflavone (table 1) [117].…”

Section: Future Perspectivementioning

confidence: 99%

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PBEF/NAMPT/Visfatin: A Promising Drug Target For Treating Rheumatoid Arthritis?

2012

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NAMPT, also known as pre-B-cell colony-enhancing factor and visfatin, has been proposed to be involved in preventing apoptosis in cancer cells and, as such, has received a great deal of attention in recent years and stimulated the development to specific inhibitors for treating cancer. The role of NAMPT inhibitors as potential therapeutic agents for other diseases has not been studied extensively. Here, we describe their applicability for treating rheumatoid arthritis. We summarize current knowledge of NAMPT expression in healthy and diseased tissues, thereafter, we focus on pathological mechanisms relevant to rheumatoid arthritis that involve the NAMPT pathway and review the current status of NAMPT inhibitors being evaluated in clinical trials.

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A fluorometric assay for high-throughput screening targeting nicotinamide phosphoribosyltransferase

Cited by 53 publications

References 45 publications

NAMPT and NAMPT-controlled NAD Metabolism in Vascular Repair

NAMPT and NAMPT-controlled NAD Metabolism in Vascular Repair

NAD replenishment with nicotinamide mononucleotide protects blood–brain barrier integrity and attenuates delayed tissue plasminogen activator‐induced haemorrhagic transformation after cerebral ischaemia

PBEF/NAMPT/Visfatin: A Promising Drug Target For Treating Rheumatoid Arthritis?

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