Different Effects of RNAi-Mediated Downregulation or Chemical Inhibition of NAMPT in an Isogenic IDH Mutant and Wild-Type Glioma Cell Model was written by Clausing, Maximilian;William, Doreen;Preussler, Matthias;Biedermann, Julia;Gruetzmann, Konrad;Richter, Susan;Buchholz, Frank;Temme, Achim;Schroeck, Evelin;Klink, Barbara. And the article was included in International Journal of Molecular Sciences in 2022.SDS of cas: 1094-61-7 The following contents are mentioned in the article:
The IDH1R132H mutation in glioma results in the neoenzymic function of IDH1, leading to the production of the oncometabolite 2-hydroxyglutarate (2-HG), alterations in energy metabolism and changes in the cellular redox household. Although shifts in the redox ratio NADPH/NADP+ were described, the consequences for the NAD+ synthesis pathways and potential therapeutic interventions were largely unexplored. Here, we describe the effects of heterozygous IDH1R132H on the redox system in a CRISPR/Cas edited glioblastoma model and compare them with IDH1 wild-type (IDH1wt) cells. Besides an increase in 2-HG and decrease in NADPH, we observed an increase in NAD+ in IDH1R132H glioblastoma cells. RT-qPCR anal. revealed the upregulation of the expression of the NAD+ synthesis enzyme nicotinamide phosphoribosyltransferase (NAMPT). Knockdown of NAMPT resulted in significantly reduced viability in IDH1R132H glioblastoma cells. Given this dependence of IDH1R132H cells on NAMPT expression, we explored the effects of the NAMPT inhibitors FK866, GMX1778 and GNE-617. Surprisingly, these agents were equally cytotoxic to IDH1R132H and IDH1wt cells. Altogether, our results indicate that targeting the NAD+ synthesis pathway is a promising therapeutic strategy in IDH mutant gliomas; however, the agent should be carefully considered since three small-mol. inhibitors of NAMPT tested in this study were not suitable for this purpose. This study involved multiple reactions and reactants, such as ((2R,3S,4R,5R)-5-(3-Carbamoylpyridin-1-ium-1-yl)-3,4-dihydroxytetrahydrofuran-2-yl)methyl hydrogen phosphate (cas: 1094-61-7SDS of cas: 1094-61-7).
((2R,3S,4R,5R)-5-(3-Carbamoylpyridin-1-ium-1-yl)-3,4-dihydroxytetrahydrofuran-2-yl)methyl hydrogen phosphate (cas: 1094-61-7) belongs to amides. Compared to amines, amides are very weak bases and do not have clearly defined acid–base properties in water. On the other hand, amides are much stronger bases than esters, aldehydes, and ketones. As a result of interactions such as these, the water solubility of amides is greater than that of corresponding hydrocarbons. These hydrogen bonds are also have an important role in the secondary structure of proteins.SDS of cas: 1094-61-7
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