Ivacaftor

• CAT Number: A000792
• CAS Number: 873054-44-5
• Molecular Formula: C24H28N2O3
• Molecular Weight: 392.5
• Purity: ≥95%
• Target: CFTR
• Solubility: >19.6mg/mL in DMSO
• Storage: -20°C
• InChI: InChI=1S/C24H28N2O3/c1-23(2,3)16-11-17(24(4,5)6)20(27)12-19(16)26-22(29)15-13-25-18-10-8-7-9-14(18)21(15)28/h7-13,27H,1-6H3,(H,25,28)(H,26,29)
• InChIKey: PURKAOJPTOLRMP-UHFFFAOYSA-N
• SMILES: O=C1C(C(NC2=C(C(C)(C)C)C=C(C(C)(C)C)C(O)=C2)=O)=CNC3=CC=CC=C31

Ivacaftor(cas 873054-44-5), also known as VX-770, is a drug used to treat cystic fibrosis in people with certain mutations in the cystic fibrosis transmembrane conductance regulator (CFTR) gene, who account for 4–5% cases of cystic fibrosis, and is included in a combination drug, lumacaftor/ivacaftor, which is used to treat people with cystic fibrosis who have the F508del mutation in CFTR. Ivacaftor is a /potentiator/ of CFTR, meaning it increases the probability that the defective channel will be open and allow chloride ions pass through the channel pore.

Reference

1: Davis PB. Therapy for cystic fibrosis–the end of the beginning? N Engl J Med. 2011 Nov 3;365(18):1734-5. PubMed PMID: 22047565.
2: Ramsey BW, Davies J, McElvaney NG, Tullis E, Bell SC, DřevÃ-nek P, Griese M, McKone EF, Wainwright CE, Konstan MW, Moss R, Ratjen F, Sermet-Gaudelus I, Rowe SM, Dong Q, Rodriguez S, Yen K, Ordoñez C, Elborn JS; VX08-770-102 Study Group. A CFTR potentiator in patients with cystic fibrosis and the G551D mutation. N Engl J Med. 2011 Nov 3;365(18):1663-72. PubMed PMID: 22047557; PubMed Central PMCID: PMC3230303.
3: Kim Chiaw P, Eckford PD, Bear CE. Insights into the mechanisms underlying CFTR channel activity, the molecular basis for cystic fibrosis and strategies for therapy. Essays Biochem. 2011 Sep 7;50(1):233-48. PubMed PMID: 21967060.
4: Pyle LC, Ehrhardt A, Mitchell LH, Fan L, Ren A, Naren AP, Li Y, Clancy JP, Bolger GB, Sorscher EJ, Rowe SM. Regulatory domain phosphorylation to distinguish the mechanistic basis underlying acute CFTR modulators. Am J Physiol Lung Cell Mol Physiol. 2011 Oct;301(4):L587-97. Epub 2011 Jul 1. PubMed PMID: 21724857; PubMed Central PMCID: PMC3191754.
5: Opar A. Excitement mounts for first disease-modifying cystic fibrosis drugs. Nat Rev Drug Discov. 2011 Jul 1;10(7):479-80. doi: 10.1038/nrd3488. PubMed PMID: 21720393.
6: Sheridan C. First cystic fibrosis drug advances towards approval. Nat Biotechnol. 2011 Jun 7;29(6):465-6. doi: 10.1038/nbt0611-465. PubMed PMID: 21654649.
7: Yu W, Chiaw PK, Bear CE. Probing conformational rescue induced by a chemical corrector of F508del-cystic fibrosis transmembrane conductance regulator (CFTR) mutant. J Biol Chem. 2011 Jul 15;286(28):24714-25. Epub 2011 May 21. PubMed PMID: 21602569; PubMed Central PMCID: PMC3137047.
8: Dolgin E. Orphan cystic fibrosis drugs find sister diseases. Nat Med. 2011 Apr;17(4):397. PubMed PMID: 21475214.
9: Dolgin E. Mutation-specific cystic fibrosis treatments on verge of approval. Nat Med. 2011 Apr;17(4):396-7. PubMed PMID: 21475213.
10: Erlinger S. Molecular repair of a defective CFTR protein in cystic fibrosis. Clin Res Hepatol Gastroenterol. 2011 Apr;35(4):254-6. Epub 2011 Feb 23. PubMed PMID: 21349786.
11: Antoniu SA. Cystic fibrosis transmembrane regulator potentiators as promising cystic fibrosis therapies. Expert Opin Investig Drugs. 2011 Mar;20(3):423-5. Epub 2011 Feb 9. PubMed PMID: 21303308.
12: Welsh MJ. Targeting the basic defect in cystic fibrosis. N Engl J Med. 2010 Nov 18;363(21):2056-7. PubMed PMID: 21083391.
13: Accurso FJ, Rowe SM, Clancy JP, Boyle MP, Dunitz JM, Durie PR, Sagel SD, Hornick DB, Konstan MW, Donaldson SH, Moss RB, Pilewski JM, Rubenstein RC, Uluer AZ, Aitken ML, Freedman SD, Rose LM, Mayer-Hamblett N, Dong Q, Zha J, Stone AJ, Olson ER, Ordoñez CL, Campbell PW, Ashlock MA, Ramsey BW. Effect of VX-770 in persons with cystic fibrosis and the G551D-CFTR mutation. N Engl J Med. 2010 Nov 18;363(21):1991-2003. PubMed PMID: 21083385; PubMed Central PMCID: PMC3148255.
14: Sloane PA, Rowe SM. Cystic fibrosis transmembrane conductance regulator protein repair as a therapeutic strategy in cystic fibrosis. Curr Opin Pulm Med. 2010 Nov;16(6):591-7. Review. PubMed PMID: 20829696.
15: Van Goor F, Hadida S, Grootenhuis PD, Burton B, Cao D, Neuberger T, Turnbull A, Singh A, Joubran J, Hazlewood A, Zhou J, McCartney J, Arumugam V, Decker C, Yang J, Young C, Olson ER, Wine JJ, Frizzell RA, Ashlock M, Negulescu P. Rescue of CF airway epithelial cell function in vitro by a CFTR potentiator, VX-770. Proc Natl Acad Sci U S A. 2009 Nov 3;106(44):18825-30. Epub 2009 Oct 21. PubMed PMID: 19846789; PubMed Central PMCID: PMC2773991.
16: Jones AM, Helm JM. Emerging treatments in cystic fibrosis. Drugs. 2009 Oct 1;69(14):1903-10. doi: 10.2165/11318500-000000000-00000. PubMed PMID: 19747007.