Inhibition of nicotinamide phosphoribosyltransferase (NAMPT), the rate-limiting enzyme of the nicotinamide adenine dinucleotide (NAD) salvage pathway, to target glioma heterogeneity through mitochondrial oxidative stress was written by Sharma, Pratibha;Xu, Jihong;Williams, Katie;Easley, Michelle;Elder, J. Brad;Lonser, Russell;Lang, Frederick F.;Lapalombella, Rosa;Sampath, Deepa;Puduvalli, Vinay K.. And the article was included in Neuro-Oncology (Cary, NC, United States) in 2022.Electric Literature of C11H15N2O8P The following contents are mentioned in the article:
Tumor-specific metabolic processes essential for cell survival are promising targets to potentially circumvent intratumoral heterogeneity, a major resistance factor in gliomas. Tumor cells preferentially using nicotinamide phosphoribosyltransferase (NAMPT), the rate-limiting enzyme in the salvage pathway for synthesis of NAD, a critical cofactor for diverse biol. processes including cellular redox reactions, energy metabolism, and biosynthesis. NAMPT is overexpressed in most malignancies, including gliomas, and can serve as a tumor-specific target. Effects of pharmacol. inhibition of NAMPT on cellular oxygen consumption rate, extracellular acidification, mitochondrial respiration, cell proliferation, invasion, and survival were assessed through in vitro and ex vivo studies on genetically heterogeneous glioma cell lines, glioma stem-like cells (GSCs), and mouse and human ex vivo organotypic glioma slice culture models. Pharmacol. inhibition of the NAD salvage biosynthesis pathway using a highly specific inhibitor, KPT-9274, resulted in the reduction of NAD levels and related downstream metabolites, inhibited proliferation, and induced apoptosis in vitro in cell lines and ex vivo in human glioma tissue. These effects were mediated by mitochondrial dysfunction, DNA damage, and increased oxidative stress leading to apoptosis in GSCs independent of genotype, IDH status, or MGMT promoter methylation status. Conversely, NAMPT inhibition had minimal in vitro effects on normal human astrocytes (NHA) and no apparent in vivo toxicity in non-tumor bearing mice. Pharmacol. NAMPT inhibition by KPT9274 potently targeted genetically heterogeneous gliomas by activating mitochondrial dysfunction. Our preclin. results provide a rationale for targeting the NAMPT-dependent alternative NAD biosynthesis pathway as a novel clin. strategy against gliomas. 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: 1094-61-7Electric Literature of C11H15N2O8P).
((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. Amides are pervasive in nature and technology. Proteins and important plastics like Nylons, Aramid, Twaron, and Kevlar are polymers whose units are connected by amide groups (polyamides); these linkages are easily formed, confer structural rigidity, and resist hydrolysis. Amides are stable compounds. The lower-melting members (such as acetamide) can be readily purified by fractional distillation. Most amides are solids which have low solubilities in water.Electric Literature of C11H15N2O8P
Referemce:
Amide – Wikipedia,
Amide – an overview | ScienceDirect Topics