Treating protein folding disorders with small molecule CFTR correctors

摘要

Novel CFTR corrector compounds that are effective in rescuing halide efflux in a cell are provided. Also provided are methods for treating protein folding disorders (e.g., cystic fibrosis). The methods include administering a CFTR corrector compound or pharmaceutically acceptable salt or prodrug thereof. Methods of screening for CFTR corrector compounds are also described herein. The methods of screening include contacting a cell that endogenously expresses a CFTR mutation with the compound to be screened and detecting a rescue of halide efflux from the cell.

主权项

1. A method for the treatment of a protein folding disorder in a subject, comprising:
administering to the subject a CFTR corrector compound, wherein the CFTR corrector compound has the following structure: or a pharmaceutically acceptable salt thereof, wherein:
R1 is hydrogen, halogen, alkoxy, substituted or unsubstituted amino, or substituted or unsubstituted alkyl; andR2, R3, and R4 are each independently substituted or unsubstituted alkyl.