ABCMdb

PMID: 20976528

Kalid O, Mense M, Fischman S, Shitrit A, Bihler H, Ben-Zeev E, Schutz N, Pedemonte N, Thomas PJ, Bridges RJ, Wetmore DR, Marantz Y, Senderowitz H
Small molecule correctors of F508del-CFTR discovered by structure-based virtual screening.
J Comput Aided Mol Des. 2010 Dec;24(12):971-91. Epub 2010 Oct 26., [PubMed]

Sentences

No. Mutations Sentence Comment

42 ABCC7 p.Gly551Asp Development at Vertex eventually resulted in the potentiator VX-770 (Phase-II and Phase-III clinical trials for CF associated with the F508del and G551D mutations, respectively, are ongoing, http://clinicaltrials.gov), and the corrector VX-809 (Phase-IIa clinical trial completed, http://clinicaltrials.gov and http://www.vrtx.com/current-projects/drug-candidates/VX-809.html). Login to comment 111 ABCC7 p.Arg1070Trp In support of this hypothesis, it has been demonstrated that the double mutant F508del/R1070W, predicted by our model to improve hydrophobic packing in this region (Fig. 7), improves the trafficking of F508del-CFTR (Philip J. Thomas, personal communication). Login to comment 134 ABCC7 p.Arg1070Trp ABCC7 p.Arg1070Trp a MOLCAD surface of the interface site. b Binding site residues (stick representation) and binding site interaction regions generated with SiteMap. Yellow hydrophobic region, blue H-bond donor region, and red H-bond acceptor region Y1073 F1074 R1070W W496 M498 V510 F1068 Fig. 7 In silico generation of the R1070W mutant in the F508del model suggests that a tryptophan in this position may restore interactions lost in the F508del mutant evaluate this large set of compounds, in vitro screening commenced with a high throughput iodide flux corrector assay [22] performed in the laboratory of Professor Luis Galietta (Advanced Biotechnology Center, Genova, Italy). Login to comment 255 ABCC7 p.Phe508Ala Solubilizing mutations and the F508A mutation present in 1XMI were mutated back to the wild-type sequence using Prime [48]. Login to comment