Division of Nutritional Sciences, University of Illinois Urbana-Champaign, Champaign, IL 61801, USA.
Cancer Center at Illinois, University of Illinois Urbana-Champaign, Champaign, IL 61801, USA.
Endocrinology. 2024 Mar 29;165(5). doi: 10.1210/endocr/bqae043.
NAD+ is one of the most important metabolites for cellular activities, and its biosynthesis mainly occurs through the salvage pathway using the nicotinamide phosphoribosyl transferase (NAMPT) enzyme. The main nicotinamide adenine dinucleotide (NAD) consumers, poly-ADP-ribose-polymerases and sirtuins enzymes, are heavily involved in DNA repair and chromatin remodeling. Since cancer cells shift their energy production pathway, NAD levels are significantly affected. NAD's roles in cell survival led to the use of NAD depletion in cancer therapies. NAMPT inhibition (alone or in combination with other cancer therapies, including endocrine therapy and chemotherapy) results in decreased cell viability and tumor burden for many cancer types. Many NAMPT inhibitors (NAMPTi) tested before were discontinued due to toxicity; however, a novel NAMPTi, KPT-9274, is a promising, low-toxicity option currently in clinical trials.
NAD+ 是细胞活动最重要的代谢物之一，其生物合成主要通过利用烟酰胺磷酸核糖转移酶（NAMPT）酶的补救途径发生。主要的烟酰胺腺嘌呤二核苷酸（NAD）消耗酶，多聚 ADP 核糖聚合酶和 Sirtuins 酶，大量参与 DNA 修复和染色质重塑。由于癌细胞改变了其能量产生途径，NAD 水平受到显著影响。NAD 在细胞存活中的作用导致了在癌症治疗中使用 NAD 耗竭。NAMPT 抑制（单独或与其他癌症治疗方法联合使用，包括内分泌治疗和化疗）导致许多癌症类型的细胞活力和肿瘤负担降低。以前测试的许多 NAMPT 抑制剂（NAMPTi）由于毒性而被停用；然而，一种新型的 NAMPTi，KPT-9274，是目前临床试验中一种有前途的、低毒性的选择。
