| 摘要: |
| 烟酰胺腺嘌呤二核苷酸(NAD)是生命体内200多种氧化还原反应的辅酶，在很多细胞生理过程中发挥着重要作用。烟酰胺磷酸核糖转移酶(Nampt)是哺乳动物NAD合成途径的限速酶，调节着细胞内的NAD水平，是生物体内进行各种生命活动和能量代谢的重要蛋白，具有多种生物学活性。在癌症中，肿瘤细胞为了快速增殖，对细胞内NAD水平的依赖比正常细胞更强。研究表明Nampt有促血管生成活性，支持着一些肿瘤细胞的生长，抑制Nampt酶活性可起到很好的抗肿瘤作用。这使得Nampt成为近年来药物研究中一个非常有吸引力的靶标，Nampt抑制剂被用于肿瘤化疗干预研究。目前有研究报道的Nampt抑制剂共4个：FK866、CHS828、CB30865、IS001。本文就近年来Nampt抑制剂在肿瘤治疗方面的研究进展进行综述，以期为Nampt调控剂的开发和应用提供参考。 |
| 关键词: 烟酰胺磷酸核糖转移酶 抑制剂 肿瘤 |
| DOI：10.3724/SP.J.1008.2012.00794 |
| 投稿时间：2012-03-23修订日期：2012-06-28 |
| 基金项目:国家重点基础研究发展计划 (“973 ” 计划, 2009CB521902), 上海市优秀学科带人计划(10XD1405300), 上海市曙光跟踪项目(10GG19)，国家“重大新药创制”科技专项(2009ZX09303-002),上海市血管生物学重点实验室开放课题 (GXY2009001001). |
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| Nicotinamide phosphoribosyltransferase inhibitors in cancer therapy: an advance |
| QIN Ye, ZHANG Ruo-yu, MIAO Chao-yu* |
(Department of Pharmacology, School of Pharmacy, Second Military Medical University, Shanghai 200433, China
*Corresponding author.) |
| Abstract: |
| Nicotinamide adenine dinucleotide (NAD) plays a crucial role in many cellular processes. It functions as a cofactor in more than 200 oxidation-reduction reactions in humans. As the rate-limiting enzyme of the predominant NAD biosynthesis pathway in mammals, nicotinamide phosphoribosyltransferase (Nampt) regulates the cellular NAD level. Nampt is a key protein in biochemical processes and energy metabolism and has various biological activities. Tumor cells are more sensitive to the NAD levels, making them more susceptible to Nampt inhibition than normal cells. Experimental evidence indicates that Nampt has proangiogenic activity and supports the growth of some tumors. These findings make Nampt attractive for pharmaceutical research during recent years, and Nampt inhibitors might be used for tumor chemotherapy. Currently 4 Nampt inhibitors have been reported: FK866, CHS828, CB30865, and IS001. Here we review the recent progress of Nampt inhibitors in cancer therapy, providing evidence for the development and application of Nampt regulating agents. |
| Key words: nicotinamide phosphoribosyltransferase inhibitor neoplasms |
