|Systematic (IUPAC) name|
|Licence data||US FDA:|
|Pregnancy cat.||B (US)|
|Legal status||-only (US)|
|Mol. mass||392.490 g/mol|
(what is this?) |
Ivacaftor (trade name Kalydeco, developed as VX-770) is a potentiator approved for patients with the G551D mutation of cystic fibrosis. Ivacaftor was developed by Vertex Pharmaceuticals in conjunction with the Cystic Fibrosis Foundation.
Cystic fibrosis is caused by any one of several defects in a protein, cystic fibrosis transmembrane conductance regulator, which regulates fluid flow within cells and affects the components of sweat, digestive fluids, and mucus. The defect, which is caused by a mutation in the individual's DNA, can be in any of several locations along the protein, each of which interferes with a different function of the protein. G551D is a standard amino acid abbreviation for a mutation in which the amino acid glycine (G) in position 551 is replaced with aspartic acid (D). G551D is characterized by a dysfunctional CFTR protein on the cell surface. In the case of G551D, the protein is trafficked to the correct area, the epithelial cell surface, but once there the protein cannot transport chloride through the channel. Ivacaftor, a CFTR potentiator, improves the transport of chloride through the ion channel by binding to the channels directly to induce a non-conventional mode of gating which in turn increases the probability that the channel is open.  
G551D accounts for only 4-5% cases of cystic fibrosis. Ivacaftor was approved by the Food and Drug Administration in January of 2012 for administration in cystic fibrosis patients having the G551D mutation.
Ivacaftor costs upwards of $294,000 for a year's supply. Vertex said it would make the drug available free to patients in the United States with no insurance and a household income of under $150,000. The drug was developed with the help of $75 million from the Cystic Fibrosis Foundation.
Ivacaftor is currently being evaluated for other cystic fibrosis mutations including F508del, the most common defect occurring in approximately 70% of the cystic fibrosis population.
- Ataluren, targeting nonsense mutations
- Lumacaftor, targeting the F508del mutation
- Jones, AM; Helm, JM (2009). "Emerging treatments in cystic fibrosis". Drugs 69 (14): 1903-10. doi:10.2165/11318500-000000000-00000. PMID 19747007.
- Phase 3 Study of VX-770 Shows Marked Improvement in Lung Function Among People with Cystic Fibrosis with G551D Mutation, Feb. 23, 2011
- Eckford, Paul (31). "CFTR POTENTIATOR VX-770 (IVACAFTOR) OPENS THE DEFECTIVE CHANNEL GATE OF MUTANT CFTR IN A PHOSPHORYLATION-DEPENDENT BUT ATP-INDEPENDENT MANNER". The Journal of Biological Chemistry.
- Van Goor, F; Hadida, S; Grootenhuis, PD; Burton, B; Cao, D; Neuberger, T; Turnbull, A; Singh, A et al. (2009). "Rescue of CF airway epithelial cell function in vitro by a CFTR potentiator, VX-770". Proceedings of the National Academy of Sciences of the United States of America 106 (44): 18825-30. doi:10.1073/pnas.0904709106. PMC 2773991. PMID 19846789. Citation uses old-style implicit et al. for authors
- Sloane, PA; Rowe, SM (2010). "Cystic fibrosis transmembrane conductance regulator protein repair as a therapeutic strategy in cystic fibrosis". Current Opinion in Pulmonary Medicine 16 (6): 591-7. doi:10.1097/MCP.0b013e32833f1d00. PMID 20829696.
- Accurso, FJ; Rowe, SM; Clancy, JP; Boyle, MP; Dunitz, JM; Durie, PR; Sagel, SD; Hornick, DB et al. (2010). "Effect of VX-770 in persons with cystic fibrosis and the G551D-CFTR mutation". The New England Journal of Medicine 363 (21): 1991-2003. doi:10.1056/NEJMoa0909825. PMID 21083385. Citation uses old-style implicit et al. for authors
- Perrone, Matthew. "Drug Approved to Treat Cystic Fibrosis' Root Cause", Associated Press, January 31, 2012.
- Flume, PA (September 2012). "Ivacaftor in subjects with cystic fibrosis who are homozygous for the F508del-CFTR mutation.". Chest 142 (3): 718-24. Accessdate used without URL
- FAQs About VX-770 from the Cystic Fibrosis Foundation
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