Resevrch progress in screening methods of calcineurin inhibitors / 中国药理学与毒理学杂志

Calcineurin inhibitor screening should benefit from the strengths of each method. This paper reviews three calcineurin inhibitor screening methods:yeast positive screening model, yeast reporter gene high through- put screening model and calcineurin activity detection method. We have compared the range of application, advantages and disadvantages of each method, and combined effect of multiple methods. The yeast positive screening model can prevent the false positiveness caused by bacteriostat by using growth zooms instead of inhibition zooms. The yeast reporter gene high through-put screening model is suitable for pilot screening among a wide range of samples and is more efficient than the other methods. The calcineurin activity detection method can directly report the inhibitory ratio to a specific target. This review is expected provide a model-selection reference for the development of novel low-toxic calcineurin inhibitors.

Signaling pathway inhibitors of calcineurin-nuclear factor of activated T cells:research progress / 中国药理学与毒理学杂志

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.

Progress of inhibitory effect of medicinal plant extracts on calcineurin / 中国药理学与毒理学杂志

Calcineurin inhibitors,such as cyclosporin A and tacroli mus,are widely-used i mmuno-suppressive drugs clinically.However,renal toxicity,hyperglycae mia and other side-effects can occur over long-term use.Isolation of novel calcineurin inhibitors fro m medicinal plants in recent years has pro-vided a new approach to the development of new immunosuppressive drugs with high efficiency and low toxicity.Recnt studies have shown that medicinal plant extracts, such as isogarcinol, quercetin, kae mpferol,phenylethanoid glycosides,ere mophilane sesquiterpenes A and B,pisiferdiol,as well as extracts fro m Smilax china L and Jasminum humile L,have obvious inhibitory effect on calcineurin.