Journal ArticleDOI
NMN/NaMN Adenylyltransferase (NMNAT) and NAD Kinase (NADK) Inhibitors: Chemistry and Potential Therapeutic Applications
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TLDR
A comprehensive summary of NMNAT and NADK inhibitors highlighting their chemical modifications by different synthetic approaches, and structure-activity relationships depending on their potential therapeutic applications is provided.Abstract:
Nicotinamide adenine dinucleotide (NAD(+)) has a crucial role in many cellular processes, both as a coenzyme for redox reactions and as a substrate to donate ADP-ribose units. Thus, enzymes involved in NAD(+) metabolism are attractive targets for drug discovery against a variety of human diseases. Herein we focus on two of them: NMN/NaMN adenylyltransferase (NMNAT) and NAD kinase (NADK). NMNAT is a key enzyme in all organisms catalyzing coupling of ATP and NMN or NaMN yielding NAD or NaAD, respectively. NADKs are ubiquitous enzymes involved in the last step of the biosynthesis of NADP. They phosphorylate NAD to produce NADP using ATP (or inorganic polyphosphates) in the presence of Mg(2+). No other pathway of NADP biosynthesis has been found in prokaryotic or eukaryotic cells. In this review we provide a comprehensive summary of NMNAT and NADK inhibitors highlighting their chemical modifications by different synthetic approaches, and structure-activity relationships depending on their potential therapeutic applications.read more
Citations
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The NAD metabolome — a key determinant of cancer cell biology
TL;DR: Given that NAD+-dependent signalling reactions involve the degradation of the molecule, permanent nucleotide resynthesis through different biosynthetic pathways is crucial for incessant cancer cell proliferation, this necessity supports the targeting of NAD metabolism as a new therapeutic concept for cancer treatment.
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New facets in the regulation of gene expression by ADP-ribosylation and poly(ADP-ribose) polymerases
TL;DR: Nature through the course of evolution has modified the PARP catalytic domain and functionalized it with a variety of other protein domains to create a set of proteins with varied activities, subcellular locations, and functions.
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Metabolic Profiling of Alternative NAD Biosynthetic Routes in Mouse Tissues
Valerio Mori,Adolfo Amici,Francesca Mazzola,Michele Di Stefano,Laura Conforti,Giulio Magni,Silverio Ruggieri,Nadia Raffaelli,Giuseppe Orsomando +8 more
TL;DR: The first comprehensive picture of the balance of the two alternative NAD biosynthetic routes in different mammalian tissues under physiological conditions is provided, filling a gap in the current knowledge of NAD biosynthesis, and provides a crucial information for the study of NAD metabolism and its role in disease.
Journal ArticleDOI
Diverse biological effects of the essential oil from Iranian Trachyspermum ammi
Luca Agostino Vitali,Daniela Beghelli,Prosper Cabral Biapa Nya,Onelia Bistoni,Loredana Cappellacci,Silvia Damiano,Giulio Lupidi,Filippo Maggi,Giuseppe Orsomando,Fabrizio Papa,Dezemona Petrelli,Riccardo Petrelli,Luana Quassinti,Leonardo Sorci,Majid Majd Zadeh,Massimo Bramucci +15 more
TL;DR: Investigating the biological effects displayed by ajwain oil, namely the antimicrobial and antioxidant activity, the cytotoxicity on tumour cells, and the induction of lymphocyte proliferation revealed some role for the ajWain oil within the network of interactions of the cells of the immune system.
Journal ArticleDOI
NAD+ Kinase as a Therapeutic Target in Cancer
Philip M. Tedeschi,Nitu Bansal,John E. Kerrigan,Emine Ercikan Abali,Kathleen W. Scotto,Joseph R. Bertino +5 more
TL;DR: The experimental evidence justifying further exploration of NADK as a clinically relevant drug target is discussed and studies with a lead compound, thionicotinamide, an NADK inhibitor prodrug are described.
References
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TL;DR: This work has been supported by the Department of the Army and the National Institutes of Health, and the author acknowledges the support and encouragement of the National Cancer Institute.
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Increased nuclear NAD biosynthesis and SIRT1 activation prevent axonal degeneration.
TL;DR: It is demonstrated that increased Nmnat activity is responsible for the axon-sparing activity of the Wlds protein and that SIRT1, a mammalian ortholog of Sir2, is the downstream effector of increased NMNat activity that leads to axonal protection.
Journal ArticleDOI
Nutrient-Sensitive Mitochondrial NAD+ Levels Dictate Cell Survival
Hongying Yang,Tianle Yang,Joseph A. Baur,Evelyn Perez,Takashi Matsui,Juan Carmona,Dudley W. Lamming,Nadja C. de Souza-Pinto,Vilhelm A. Bohr,Anthony Rosenzweig,Rafael de Cabo,Anthony A. Sauve,David A. Sinclair +12 more
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