| 主权项 |
1. A method of treating cystic fibrosis in a patient, comprising the step of: administering to said patient a corrector agent capable of acting through the membrane spanning domain 1 (MSD1) during the biosynthesis of a CFTR protein, provided that the corrector agent is not a compound listed in Table 1, wherein said action is characterized in vitro by one or more of the following:
(i) an increase in accumulation of fragment CFTR375 in a cell expressing said fragment the presence of said corrector compared to such accumulation of fragment CFTR375 in a cell expressing said fragment in the absence of said corrector, (ii) an increase in accumulation of fragment CFTR380 in a cell expressing said fragment in the presence of said corrector compared to such accumulation of fragment CFTR380 in a cell expressing said fragment in the absence of said corrector, (iii) an increase in the half-life of fragment CFTR375 in a cell expressing said fragment in the presence of said corrector compared to such half-life of fragment CFTR375 in a cell expressing said fragment in the absence of said corrector, (iv) an increase in the half-life of fragment CFTR380 in a cell expressing said fragment in the presence of said corrector compared to such half-life of fragment CFTR380 in a cell expressing said fragment in the absence of said corrector, (v) an increase in the half-life of fragment CFTR380, CFTR430, and/or CFTR653 in a cell expressing CFTR380, CFTR430, and/or CFTR653 in the presence of said corrector compared to the half-life of CFTR380, CFTR430, and/or CFTR653, respectively, in a cell expressing said fragment in the absence of said corrector, or, or (vi) an enhanced resistance of fragment CFTR380 to proteolysis with trypsin in the presence of said corrector compared to such proteolysis in the absence of said corrector. |
