集成技术Issue(4)：28-44,17.
化学修饰的环孢菌素类非免疫抑制性亲环素抑制剂进展
Nonimmunosuppressive Cyclophilin Inhibitors Derived from the Cyclosporin Scaffolds
摘要
Abstract
Cyclophilins (Cyps) are crucial to protein folding because that the ubiquitous proteins affect the cis-trans isomerization of Pro amide bonds. The immunosuppressive natural product cyclosporine A inhibits the enzymatic activity of the cyclophilins. Chemical modiifcation of cyclosporine scaffolds has produced many analogues that inhibit cyclophilins in vitro but have reduced immunosuppressive properties. Three nonimmunosuppressive cyclophilin inhibitors (alisporivir, SCY-635, and NIM811) have demonstrated clinical efifcacy for the treatment of hepatitis C infection. Recent publications suggest that cyclophilin inhibitors may have utility for the treatment of diverse viral infections, inlfammatory indications, and cancer. In this review, we document the structure-activity relationships of the nonimmunosuppressive cyclosporins in clinical and preclinical development. Aspects of the pharmacokinetic behavior and chemical biology of these drug candidates are also described.关键词
亲环素/环孢菌素A/非免疫抑制/抗病毒/构效关系Key words
cyclophilins/cyclosporine A/nonimmunosuppressive/antiviral/structure-activity relationships分类
医药卫生引用本文复制引用
姚贵阳,房丽晶,潘正银,王恒山,粟武..化学修饰的环孢菌素类非免疫抑制性亲环素抑制剂进展[J].集成技术,2015,(4):28-44,17.基金项目
深圳市引进海外高层次人才“孔雀计划”(KQCX20130628112914285)；国家自然科学基金(21432003) （KQCX20130628112914285）
