Nampt/Visfatin/PBEF: A Functionally Multi-faceted Protein with a Pivotal Role in Malignant Tumors

He      Jieyu; Tu      Chao; Li      Mengjun; Wang      Shalong; Guan      Xiaomei; Lin      Jianfeng; Li      Zhihong

doi:10.2174/138161212803582531

Abstract

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.

Keywords: Nampt, visfatin, PBEF, malignant tumors, mechanism, angiogenesis, therapy, NAD+ biosynthesis, energy metabolism, clinical trials.