CFTR potentiators: from bench to bedside

Kang Yang Jih, Wen Ying Lin, Yoshiro Sohma, Tzyh Chang Hwang

研究成果: Review article同行評審

26 引文 斯高帕斯(Scopus)


One major breakthrough in cystic fibrosis research in the past decade is the development of drugs that target the root cause of the disease — dysfunctional CFTR protein. One of the compounds, Ivacaftor or Kalydeco, which has been approved for clinical use since 2012, acts by promoting the gating function of CFTR. Our recent studies have led to a gating model that features an energetic coupling between NBD dimerization and gate opening/closing in CFTR's TMDs. Based on this model, we showed that ATP analogs can enhance CFTR gating by facilitating NBD dimerization, whereas Ivacaftor works by stabilizing the open channel conformation of the TMDs. This latter idea also explains the near omnipotence of Ivacaftor. Furthermore, this model marks multiple approaches to synergistically boost the open probability of CFTR by influencing distinct molecular events that control gating conformational changes.

頁(從 - 到)98-104
期刊Current Opinion in Pharmacology
出版狀態Published - 6月 2017


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