靶向 NAD+ 代谢：潜在癌症治疗策略的临床前见解

IF 3.8 3区医学 Q2 ENDOCRINOLOGY & METABOLISM

Endocrinology Pub Date : 2024-04-03 DOI:10.1210/endocr/bqae043

A. Mogol, A. Z. Kaminsky, David J Dutton, Zeynep Madak Erdogan

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引用次数: 0

摘要

NAD+ 是细胞活动最重要的代谢物之一，其生物合成主要通过使用 NAMPT 酶的挽救途径进行。NAD 的主要消耗者 PARP 和 SIRT 酶在很大程度上参与了 DNA 修复和染色质重塑。由于癌细胞改变了能量生成途径，因此 NAD 水平受到了很大影响。NAD 在细胞存活中的作用促使人们在癌症疗法中使用 NAD 消耗疗法。抑制 NAMPT（单独使用或与其他癌症疗法（包括内分泌疗法和化疗）联合使用）可降低许多癌症类型的细胞存活率和肿瘤负荷。以前测试过的许多 NAMPT 抑制剂（NAMPTi）都因毒性问题而停产；不过，一种新型 NAMPTi KPT-9274 是一种前景看好的低毒性选择，目前正在进行临床试验。

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Targeting NAD+ metabolism: Pre-clinical insights into potential cancer therapy strategies.

NAD+ is one of the most important metabolites for cellular activities, and its biosynthesis mainly occurs through the salvage pathway using the NAMPT enzyme. The main NAD consumers, PARP and SIRT 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.

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来源期刊

Endocrinology 医学-内分泌学与代谢

CiteScore

8.10

自引率

4.20%

发文量

195

审稿时长

2-3 weeks

期刊介绍： The mission of Endocrinology is to be the authoritative source of emerging hormone science and to disseminate that new knowledge to scientists, clinicians, and the public in a way that will enable "hormone science to health." Endocrinology welcomes the submission of original research investigating endocrine systems and diseases at all levels of biological organization, incorporating molecular mechanistic studies, such as hormone-receptor interactions, in all areas of endocrinology, as well as cross-disciplinary and integrative studies. The editors of Endocrinology encourage the submission of research in emerging areas not traditionally recognized as endocrinology or metabolism in addition to the following traditionally recognized fields: Adrenal; Bone Health and Osteoporosis; Cardiovascular Endocrinology; Diabetes; Endocrine-Disrupting Chemicals; Endocrine Neoplasia and Cancer; Growth; Neuroendocrinology; Nuclear Receptors and Their Ligands; Obesity; Reproductive Endocrinology; Signaling Pathways; and Thyroid.