کد مقاله | کد نشریه | سال انتشار | مقاله انگلیسی | نسخه تمام متن |
---|---|---|---|---|
6240660 | 1280433 | 2015 | 10 صفحه PDF | دانلود رایگان |
BackgroundSmall molecules as shown by VX809 can rescue the mislocalization of F508del-CFTR. The aim of this study was to identify correctors with a clinical history and their targets of action.MethodsCFTR correctors were screened using two F508del-CFTR expressing cell based HTS assays. Electrophysiological studies using CFBE41oâ and HBE cells and in-vivo mouse assays confirmed CFTR rescue. The target of action was attained using pharmacological inhibitors and siRNA to specific genes.ResultsIbuprofen was identified as a CFTR corrector. Ibuprofen treatment of polarized CFBE41oâ monolayers increased the short-circuit current (Isc) response to stimulation. In vivo CF mice treatment with ibuprofen restored the CFTR trafficking. SiRNA knock down of cyclooxygenase expression caused partial F508del-CFTR correction.ConclusionThese studies show that ibuprofen is a CFTR corrector and that it causes correction by COX-1 inhibition. Hence ibuprofen may be suitable to be part of a future CF combination therapy.
Journal: Journal of Cystic Fibrosis - Volume 14, Issue 1, January 2015, Pages 16-25