Signaling pathway inhibitors of calcineurin-nuclear factor of activated T cells:research progress

VernacularTitle:钙调磷酸酶-活化T细胞核因子信号通路抑制剂的研究进展
Author: Pengfei WU ; Junlin LIU ; Zhifeng CUI
Publication Type:Journal Article
Keywords: calcineurin; nuclear factor of activated T cells; immunosuppressants; ciclosporin A; tacrolimus
From: Chinese Journal of Pharmacology and Toxicology 2016;30(4):397-404
CountryChina
Language:Chinese
Abstract: Calcineurin (CaN) serves as a key enzyme in human immune regulation. The most important target of this enzyme is the transcription factors of nuclear factors of activated T cells (NFATc). The discovery of the immunosuppressive function of CaN inhibitors (CNIs),ciclosporin A (CsA) and tacrolimus (FK506),has helped overcome the immune rejection of organ transplantion and changed organ transplantion fundamentally. Both of these drugs are still widely used in clinical and basic research,but their therapeutic effects are limited by their serious side effects,including renal tox?icity and neurotoxicity. Therefore,the development of new CNIs with higher specificity and fewer side effects in the clinic is a focus of research. In this paper,the newly discovered and synthesized CNIs in recent decades,including the CsA and FK506 derivatives,direct inhibitors of CaN,as well as the inhibitors that specifically interfere with CaN-NFATc interaction,were summarized.