ABCMdb

PMID: 17573123

Amaral MD, Kunzelmann K
Molecular targeting of CFTR as a therapeutic approach to cystic fibrosis.
Trends Pharmacol Sci. 2007 Jul;28(7):334-41. Epub 2007 Jun 18., [PubMed]

Sentences

No. Mutations Sentence Comment

46 ABCC7 p.Gly542* Class I mutations, which abrogate protein production, often include mutations that generate premature stop codons (e.g. G542X) that lead to mRNA degradation by nonsense-mediated decay. Login to comment 48 ABCC7 p.Gly551Asp Class III mutants affect channel regulation, impairing channel opening (e.g. G551D). Login to comment 49 ABCC7 p.Arg334Trp Class IV mutants exhibit reduced conduction: that is, decreased flow of ions (e.g. R334W). Login to comment 119 ABCC7 p.Gly551Asp One study could not detect any activating effects of MPB-07 on G551D-CFTR [43]. Login to comment 134 ABCC7 p.Gly551Asp Although the naturally derived flavone apigenin remains the most potent activator of G551D-CFTR [46], the novel classes of isoxazolones and isoxazolines might deliver higher-potency compounds [47]. Login to comment 135 ABCC7 p.Gly551Asp ABCC7 p.Gly1349Asp Phenylglycines and sulfonamides (potencies >100 nM) improve F508del-CFTR, G551D-CFTR and G1349D-CFTR gating, but only after cAMP activation [48,49]. Login to comment 141 ABCC7 p.Gly551Asp The pyrazole VX-532 is among the most potent and efficacious potentiators of F508del-CFTR and G551D-CFTR [19]. Login to comment 142 ABCC7 p.Gly551Asp Pyrrolopyrazinederivatives (6-phenylpyrrolo[2,3-b]pyrazines) such as 7-N-butyl-6-(4-hydroxyphenyl)[5H]pyrrolo[2,3-b]pyrazine (RP107) potentiate wild-type CFTR, G551D-CFTR and F508del-CFTR in human airway epithelial cells and colonic epithelium [37]. Login to comment 148 ABCC7 p.Gly551Asp Genistein is also effective in human nasal epithelia - particularly on G551D-CFTR - restoring ENaC downregulation but, at higher concentrations, it inhibits ion transport [38,39]. Login to comment 152 ABCC7 p.Gly551Asp Although it acts on transient receptor potential receptors and influences intracellular Ca2+ -signaling, capsaicin directly activates wild-type CFTR, G551D-CFTR and F508del-CFTR as effectively as does genistein and with a similar mechanism of action. Login to comment