ABCMdb

PMID: 23380248

Hanrahan JW, Sampson HM, Thomas DY
Novel pharmacological strategies to treat cystic fibrosis.
Trends Pharmacol Sci. 2013 Feb;34(2):119-25. doi: 10.1016/j.tips.2012.11.006., [PubMed]

Sentences

No. Mutations Sentence Comment

40 ABCC7 p.Ile539Thr ABCC7 p.Gly550Glu The suppressor mutations G550E and I539T restore the DF508-CFTR proteolytic pattern to that of wild type CFTR. Login to comment 89 ABCC7 p.Gly551Asp Vertex Pharmaceuticals has launched the CFTR potentiator VX-770 (Kalydeco) that is suitable for a subset of patients (1200 worldwide) who carry the G551D-CFTR mutation. Login to comment 140 ABCC7 p.Gly622Asp VRT-325 and VRT-532 modify the activity of purified reconstituted CFTR channels [48,49], whereas MPB compounds activate CFTR channels when added acutely [45], but not the G622D mutant. Login to comment 145 ABCC7 p.Arg1070Trp The two-step folding hypothesis also suggests a rational way to test for new pharmacological chaperones that act at each step: pharmacological chaperones that correct NBD1 conformational stability should be additive, with mutations such as R1070W that restore contacts between NBD1 and MSD2 (CL4). Login to comment 146 ABCC7 p.Phe429Ser ABCC7 p.Phe494Asn ABCC7 p.Gln637Arg Conversely, pharmacological chaperones that restore the interface between NBD1 and MSD2 should be additive with the three solubilizing (3S) mutant in NBD1 (F494N, Q637R, F429S) [11]. Login to comment 161 ABCC7 p.Gly551Asp It is very effective against the correctly trafficked but incorrectly activated G551D-CFTR mutant, and it has been reported to potentiate the activity of several other gating mutants [54]. Login to comment 255 ABCC7 p.Gly551Asp 11, 237-245 55 Ramsey, B.W. et al. (2011) A CFTR potentiator in patients with cystic fibrosis and the G551D mutation. Login to comment