Department of Orthopedics, The Second Xiangya Hospital of Central South University, Changsha, China.
Curr Pharm Des. 2012;18(37):6123-32. doi: 10.2174/138161212803582531.
Nampt/Visfatin/PBEF is a primary, rate-limiting enzyme involved in NAD+ biosynthesis, which serves as a pivotal substance for proteins, and is required for cell growth, survival, DNA replication and repair and energy metabolism. Growing researches have elucidated that it is a pleiotropic protein that functions not only as an enzyme, but also as an adipocytokin, a growth factor, and a cytokine. Additionally, accumulated evidences indicate that Nampt is correlated to various malignant tumors, and complicated mechanisms are proposed to be involved in the carcinogenesis, progression, invasion and metastasis of it, including regulation of energy metabolism and genome instability, promotion of proliferation, angiogenesis, and tumor-promoting inflammation, resistance in cell death and avoidance of immune destruction. APO866 and CHS-828 are recognized inhibitors of Nampt, known to block the intracellular and extracellular NAD+ synthesis pathway. Both of them are currently in clinical trials for the treatment of various malignant tumors and have been shown to represent novel promising antitumor chemotherapeutic agents.
NAMPT/Visfatin/PBEF 是一种主要的限速酶，参与 NAD+的生物合成，它是蛋白质的关键物质，是细胞生长、存活、DNA 复制和修复以及能量代谢所必需的。越来越多的研究表明，它是一种多功能蛋白，不仅作为一种酶，而且作为一种脂肪细胞因子、生长因子和细胞因子发挥作用。此外，越来越多的证据表明，NAMPT 与各种恶性肿瘤相关，并且提出了复杂的机制参与其致癌、进展、侵袭和转移，包括调节能量代谢和基因组不稳定性、促进增殖、血管生成和肿瘤促进炎症、细胞死亡抵抗和避免免疫破坏。APO866 和 CHS-828 被认为是 NAMPT 的抑制剂，可阻断细胞内和细胞外 NAD+合成途径。两者目前都在临床试验中用于治疗各种恶性肿瘤，并已被证明是有前途的新型抗肿瘤化疗药物。
