ABCMdb

PMID: 23060795

Pedemonte N, Galietta LJ
Pharmacological Correctors of Mutant CFTR Mistrafficking.
Front Pharmacol. 2012 Oct 5;3:175. doi: 10.3389/fphar.2012.00175. eCollection 2012., [PubMed]

Sentences

No. Mutations Sentence Comment

27 ABCC7 p.Gly551Asp One of these potentiators, VX-770, identified by Vertex Pharmaceuticals (Van Goor et al., 2009) has been particularly successful in clinical trials in patients with G551D (Ramsey et al.,2011),a mutation characterized by very low channel activity but with normal protein trafficking. Login to comment 28 ABCC7 p.Gly551Asp The drug (named Kalydeco) has been recently approved by the FDA to treat G551D patients. Login to comment 64 ABCC7 p.Gly551Asp However, the efficacy of the drug in vivo in ࢞F508 patients (Clancy et al., 2012) is significantly lower than that of the potentiator VX-770 in G551D patients (Ramsey et al., 2011). Login to comment 65 ABCC7 p.Gly551Asp For example, the lowering of chloride concentration in sweat, a good indicator of CFTR activity in vivo, was 48 mM for VX-770 in G551D patients and 8 mM for VX-809 in ࢞F508 patients. Login to comment 67 ABCC7 p.Gly551Asp These results highlight the particular difficulty in correcting the trafficking defect of the ࢞F508 mutation with respect to the gating defect of G551D. Login to comment 83 ABCC7 p.Gly551Asp Subsequently, synthesis of new derivatives identified MPB-91 as a potent activator of G551D-CFTR (Derand et al., 2001). Login to comment 144 ABCC7 p.Ile539Thr ABCC7 p.Arg555Lys The first type of mutation,such as I539T or R555K,increases the stability of NBD1. Login to comment 145 ABCC7 p.Arg1070Trp The second type of mutation, namely R1070W, improves the interaction of NBD1 with CL4 by providing an aromatic group that compensates for the lack of F508. Login to comment