- A fluorometric assay for high-throughput screening targeting nicotinamide phosphoribosyltransferase
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Nicotinamide adenine dinucleotide (NAD) plays a crucial role in many cellular processes. As the rate-limiting enzyme of the predominant NAD biosynthesis pathway in mammals, nicotinamide phosphoribosyltransferase (Nampt) regulates the cellular NAD level. Tumor cells are more sensitive to the NAD levels, making them more susceptible to Nampt inhibition than their nontumorigenic counterparts. Experimental evidence has indicated that Nampt might have proangiogenic activity and supports the growth of some tumors, so Nampt inhibitors may be promising as antitumor agents. However, only four Nampt inhibitors have been reported, and no high-throughput screening (HTS) strategy for Nampt has been proposed to date, largely limiting the drug discovery targeting Nampt. Therefore, the development of a robust HTS strategy for Nampt is both imperative and significant. Here we developed a fluorometric method for a Nampt activity assay by measuring the fluorescence of nicotinamide mononucleotide (NMN) derivative resulting from the enzymatic product NMN through simple chemical reactions. Then we set up an HTS system after thorough optimizations of this method and validated that it is feasible and effective through a pilot screening on a small library. This HTS system should expedite the discovery of Nampt inhibitors as antitumor drug candidates.
- Zhang, Ruo-Yu,Qin, Ye,Lv, Xiao-Qun,Wang, Pei,Xu, Tian-Ying,Zhang, Lei,Miao, Chao-Yu
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- A novel preparation of nicotinamide mononucleotide
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Nicotinamide mononucleotide is conveniently prepared from nicotinamide adenine dinucleotide by specific hydrolysis of the pyrophosphate bond using the Zr4+ ion as catalyst.
- Liu,Visscher
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- Nicotinamide-Containing Di- and Trinucleotides as Chemical Tools for Studies of NAD-Capped RNAs
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We report the chemical synthesis of a set of nicotinamide adenine dinucleotide (NAD) cap analogues containing chemical modifications that reduce their susceptibility to NAD-RNA-degrading enzymes. These analogues can be incorporated into transcripts in a similar way as NAD. Biochemical characterization of RNAs carrying these caps with DXO, NudC, and Nudt12 enzymes led to the identification of compounds that can be instrumental in unraveling so far unaddressed biological aspects of NAD-RNAs.
- Mlynarska-Cieslak, Agnieszka,Depaix, Anais,Grudzien-Nogalska, Ewa,Sikorski, Pawel J.,Warminski, Marcin,Kiledjian, Megerditch,Jemielity, Jacek,Kowalska, Joanna
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- A chemical synthesis of nicotinamide adenine dinucleotide (NAD+)
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A practical synthesis of nicotinamide mononucleotide (β-NMN) and a high yield coupling with AMP-morpholidate that also provides NAD+ in an efficient manner are reported.
- Lee, Jaemoon,Churchil, Hywyn,Choi, Woo-Baeg,Lynch, Joseph E.,Roberts,Volante,Reider, Paul J.
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- Enzymatic and chemical syntheses of vacor analogs of nicotinamide riboside, nmn and nad
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It has recently been demonstrated that the rat poison vacor interferes with mammalian NAD metabolism, because it acts as a nicotinamide analog and is converted by enzymes of the NAD salvage pathway. Thereby, vacor is transformed into the NAD analog vacor adenine dinucleotide (VAD), a molecule that causes cell toxicity. Therefore, vacor may potentially be exploited to kill cancer cells. In this study, we have developed efficient enzymatic and chemical procedures to produce vacor analogs of NAD and nicotinamide riboside (NR). VAD was readily generated by a base-exchange reaction, replacing the nicotinamide moiety of NAD by vacor, catalyzed by Aplysia californica ADP ribosyl cyclase. Additionally, we present the chemical synthesis of the nucleoside version of vacor, vacor riboside (VR). Similar to the physiological NAD precursor, NR, VR was converted to the corresponding mononucleotide (VMN) by nicotinamide riboside kinases (NRKs). This conversion is quantitative and very efficient. Consequently, phosphorylation of VR by NRKs represents a valuable alternative to produce the vacor analog of NMN, compared to its generation from vacor by nicotinamide phosphoribosyltransferase (NamPT).
- Sverkeli, Lars Jansen,Hayat, Faisal,Migaud, Marie E.,Ziegler, Mathias
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- PRODUCTION OF NMN AND ITS DERIVATIVES VIA MICROBIAL PROCESSES
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The present invention relates to microbial production of nicotinamide mononucleotide (NMN), nicotinamide riboside (NR), and nicotinamide adenine dinucleotide (NAD) using a genetically modified bacterium.
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Paragraph 0028-0029; 0032-0036; 0070-0074; 0083
(2021/11/13)
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- Chemical synthesis method of NMN
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The invention discloses a chemical synthesis method of NMN. The synthesis method comprises the following steps: firstly, enabling ribofuranose and niacinamide to react; then enabling a generated compound to react with metaphosphate; after reacting, acidifying; and then purifying to obtain the high-purity NMN. Compared with enzymatic reaction, the synthesis method disclosed by the invention has the advantages of low raw material cost, moderate and stable technological conditions and easiness for controlling; indexes of products of different batches are close and the reaction productivity is easy to improve; and compared with a fermentation method, the product obtained by the preparation method has high safety and the application prospect of the product is improved.
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Paragraph 0035; 0038; 0045-0046; 0047; 0054-0055; 0056; ...
(2021/06/21)
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- Method for preparing nicotinamide mononucleotide (NMN)
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The present invention provides a method for preparing nicotinamide mononucleotide (NMN) by bioanalysis. The method includes a step of catalytically reacting a plurality of raw materials including nicotinamide, ATP, and ribose in the presence of nicotinamide phosphoribosyltransferase (Nampt), ribose phosphate pyrophosphokinase, and ribokinase, to prepare the NMN.
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Page/Page column 4-6
(2021/06/23)
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- Preparation method of beta-nicotinamide mononucleotide
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The invention discloses a preparation method of beta-nicotinamide mononucleotide. According to the method disclosed by the invention, the beta-nicotinamide mononucleotide is prepared by taking a compound shown as a formula II as a raw material and sequentially carrying out glycosylation condensation, deprotection, phosphorylation and acylation protection group removal reaction. Compared with methods in the prior art, the method provided by the invention has the advantages of high yield, simple operation, easy purification of intermediates, good phosphorylation selectivity and the like.
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- Chemical synthesis method of beta-nicotinamide mononucleotide
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The invention provides a chemical synthesis method of beta-nicotinamide mononucleotide. The method comprises the following steps: taking 1, 2, 3, 5-tetrabenzoyloxy-2-C-methyl-beta-D-ribofuranose and nicotinamide as initial raw materials, and sequentially carrying out condensation reaction, benzoyl protecting group removal and phosphorylation reaction, so as to prepare the beta-nicotinamide mononucleotide. The high-purity beta-nicotinamide mononucleotide can be obtained through three steps of reaction (each step of reaction does not need purification) and one step of desalination purification. The method has the advantages of easily available raw materials, short reaction route, simple post-treatment, environmental protection and high total reaction yield, and is suitable for industrial production.
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Paragraph 0040; 0046-0049
(2021/11/10)
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- Β - nicotinamide mononucleotide preparation method
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The invention discloses a preparation method of β - nicotinamide mononucleotide. The preparation method of β - nicotinamide mononucleotide comprises the following steps: S1: in the presence of first solvent and catalyst, nicotinate and tetraacetyl - D - ribose undergo condensation reaction in first microchannel reactor to obtain the material A. The temperature of the condensation reaction is 51 - 80 °C, and the residence time of the condensation reaction is 0.5 - 10 min. S2: Material A Removal first of the solvent gives material B. S3: In the presence of second solvent, the material B and the liquid ammonia are subjected to an ammonolysis reaction to obtain the material C. S4: The mixture of material C and third solvent removed second solvent and unreacted liquid ammonia to give material D. S5: The material D phosphorylates and reacts with the phosphorylation auxiliary to obtain. The β - nicotinamide mononucleotide preparation method can effectively shorten the reaction time, improve the production efficiency, lower the side reaction and improve the product yield.
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Paragraph 0019; 0091; 0100-0104; 0113-0117; 0126-0130; ....
(2021/10/27)
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- Synthesis method of beta-nicotinamide mononucleotide
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The invention discloses a synthesis method of beta-nicotinamide mononucleotide, and relates to the technical field of drug synthesis. The synthesis method mainly comprises the following steps of S1, mixing and reacting nicotinamide, hexamethyldisilazane and a catalyst I in a reaction kettle to obtain silanization-protected nicotinamide; S2, adding tetraacetyl ribose, a solvent, a catalyst II and methanol for reaction so as to generate nicotinamide triacetyl riboside; S3, adding methanol and n-propylamine to generate nicotinamide riboside; S4, adding trimethyl phosphate and phosphorus oxychloride to generate beta-nicotinamide mononucleotide; and S5, separating and purifying the beta-nicotinamide mononucleoside acid. According to the invention, a plurality of continuous steps are controlledto be carried out in one reaction container, and the steps of separating and purifying an intermediate are avoided, so that the method has the advantages of high yield and high production efficiency.
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Paragraph 0027-0032
(2020/09/20)
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- Preparation method of beta-nicotinamide mononucleotide
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The invention relates to the technical field of medicines, and provides a preparation method of beta-nicotinamide mononucleotide. The preparation method comprises the steps of A: performing a phosphorylation reaction: in an aqueous alkaline solution of which the pH is 8-10, and under the condition that the temperature of a reaction system is 25-50 DEG C, enabling nicotinamide riboside and metaphophate to be subjected to the phosphorylation reaction for 2-5h, to obtain an intermediate product of the nicotinamide mononucleotide; B, performing an acidification reaction: adding acid to the reaction solution, regulating the pH value to 3-5, reducing the temperature of the reaction system, and performing acidification on the intermediate product of the beta-nicotinamide mononucleotide to obtainthe beta-nicotinamide mononucleotide; and C, purifying products: sequentially performing filtration with a protein membrane, concentration with a high-pressure desalination membrane, separation and purification with anion exchange resins and concentration and crystallizing on the reaction solution obtained in the step B to obtain pure products of the beta-nicotinamide mononucleotide.
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Paragraph 0030-0052
(2020/07/24)
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- Method of preparing beta-nicotinamide mononucleotide and sodium salt thereof
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The invention relates to the field of chemical synthesis, in particular to a method for preparing beta-nicotinamide mononucleotide and sodium salt thereof. The method includes: subjecting beta-nicotinamide ribose and diphenyl chlorophosphate to esterification reaction, performing hydrolysis phenyl removing reaction to obtain beta-nicotinamide nucleotide, and adding a certain amount of alkali to the beta-nicotinamide nucleotide to perform alkalization to obtain beta-nicotinamide ribonucleotide sodium. The method is simple to operate, easy to achieve large-scale production, low in cost, good infinal product quality and the like.
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- Process preparation method of beta-nicotinamide mononucleotide
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The invention provides a process preparation method of beta-nicotinamide mononucleotide. With tetraacetylribose and niacinamide or ethyl nicotinate as starting materials, through main process steps ofcondensation, ammonolysis, chemical resolution, phosphorylation and the like, and through optimization of the process method, the beta-nicotinamide mononucleotide is prepared; the method is based onthe purposes of quality control and safety of the beta-nicotinamide mononucleotide, industrial batch production feasibility of a preparation process and the like; the preparation method is improved onthe basis of an original process route, optimizes the selected materials and reagents, controls the material amount and the like, and has the advantages of simplicity in operation, easiness in process amplification, higher yield, controllable final product quality, controllable safety and the like compared with the original preparation process.
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Paragraph 0108-0109
(2020/08/26)
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- EFFICIENT AND SCALABLE SYNTHESES OF NICOTINOYL RIBOSIDES AND REDUCED NICOTINOYL RIBOSIDES, MODIFIED DERIVATIVES THEREOF, PHOSPHORYLATED ANALOGS THEREOF, ADENYLYL DINUCLEOTIDE CONJUGATES THEREOF, AND NOVEL CRYSTALLINE FORMS THEREOF
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The present disclosure provides methods of making nicotinoyl riboside compounds or derivatives of formula (I): wherein X?, Z1, Z2, n, R1, R2, R3, R4, R5, R6, R7, and R8 are described herein, reduced analogs thereof, modified derivatives thereof, phosphorylated analogs thereof, and adenylyl dinucleotide conjugates thereof, or salts, solvates, or prodrugs thereof; and novel crystalline forms thereof.
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Paragraph 2748-2751
(2018/05/26)
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- Method for preparing niacinamide nucleoside salt
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The invention relates to a method for preparing niacinamide nucleoside salt. The method comprises the following steps: replacing ions by niacinamide nucleoside trifluoromethane sulfonate prepared by deacetylation of triacetyl niacinamide nucleoside trifluoromethane in an organic solvent with acids, crystallizing to separate out a crude product, and pulping, thereby obtaining the corresponding niacinamide nucleoside salt. The ion replacement process in the invention overcomes the defects of chemical methods and extraction methods, and is suitable for industrial production.
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Paragraph 0039-0040; 0043; 0046
(2018/12/02)
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- DUAL-ACTIVITY NICOTINAMIDE PHOSPHORIBOSYLTRANSFERASE INHIBITORS
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The present disclosure describes NAMPT modulatory compounds, and methods of identifying NAMPT modulatory compounds. The present disclosure also describes methods of testing NAMPT modulatory compounds for NTPase activity, cell mobility modulatory activity, and cell metastasis modulatory activity.
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Paragraph 00128; 00135; 00138;
(2018/05/24)
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- Method for preparing beta-niacinamide single nucleotide or beta-niacinamide ribose
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The invention belongs to the field of chemical synthesis, and particularly relates to a method for preparing beta-niacinamide single nucleotide or beta-niacinamide ribose, which aims at solving the technical problem of providing a method for preparing beta-niacinamide single nucleotide or beta-niacinamide ribose. The method comprises the following steps of performing condensation, deacetylation, phosphorylation and ammonolysis on ethyl niacinate and tetraacetyl ribose, so as to obtain the beta-niacinamide single nucleotide; performing condensation, deacetylation, and ammonolysis on ethyl niacinate and tetraacetyl ribose, so as to obtain the beta-niacinamide ribose. Compared with the conventional methods, the method has the advantages that the operation is simple, the amplification is easy,the purification is easy, the yield rate is high, and the like.
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Paragraph 0085; 0092-0095; 0102-0104
(2019/01/14)
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- PROCESS FOR PREPARATION OF NICOTINAMIDE RIBOSIDE (NR) AND COSMETIC COMPOSITION COMPRISING (NR AND A PHOSPHATE-BINDING AGENT
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Disclosed herein is a process for preparing nicotinamide riboside (NR) from an NR precursor and a phosphate-binding agent in a solvent. The reaction-derived mixture comprising NR may be further used without further processing in a variety of products, particularly in a cosmetic product.
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Page/Page column 22
(2017/09/15)
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- Synthesis of phosphodiester-type nicotinamide adenine dinucleotide analogs
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Fourteen phosphodiester-type β-nicotinamide adenine dinucleotide (NAD+) analogs were prepared starting from nicotinamide. The phosphodiester linkage was effectively assembled in 69-93% yields via condensation reaction between 2′,3′-di-O-acetyl nicotinamide mononucleotide and alcohols in the presence of 2,4,6-triisopropylbenzenesulfonyl chloride. The analog β-nicotinamide ribose-5-(2-phenylethyl) phosphate showed beneficial effects on cell growth of model microorganisms.
- Liu, Wujun,Wu, Siguo,Hou, Shuhua,Zhao, Zongbao (Kent)
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scheme or table
p. 8378 - 8383
(2009/12/28)
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