lumacaftor   

GtoPdb Ligand ID: 7481

Synonyms: VRT-826809 | VX-809 | VX809
lumacaftor is an approved drug (EMA & FDA (2015))
Compound class: Synthetic organic
Comment: Lumacaftor is termed a cystic fibrosis transmembrane conductance regulator (CFTR) corrector, acting to reduce mis-folding of the defective F508del mutant CFTR protein, in comparison to ivacaftor which is termed a CFTR potentiator drug. The F508del mutation is the most common cause of cystic fibrosis and accounts for approximately 60% of CF patients in Europe.
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2D Structure
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Physico-chemical Properties
Hydrogen bond acceptors 5
Hydrogen bond donors 2
Rotatable bonds 6
Topological polar surface area 97.75
Molecular weight 452.12
XLogP 4.93
No. Lipinski's rules broken 0
SMILES / InChI / InChIKey
Canonical SMILES O=C(C1(CC1)c1ccc2c(c1)OC(O2)(F)F)Nc1ccc(c(n1)c1cccc(c1)C(=O)O)C
Isomeric SMILES O=C(C1(CC1)c1ccc2c(c1)OC(O2)(F)F)Nc1ccc(c(n1)c1cccc(c1)C(=O)O)C
InChI InChI=1S/C24H18F2N2O5/c1-13-5-8-19(27-20(13)14-3-2-4-15(11-14)21(29)30)28-22(31)23(9-10-23)16-6-7-17-18(12-16)33-24(25,26)32-17/h2-8,11-12H,9-10H2,1H3,(H,29,30)(H,27,28,31)
InChI Key UFSKUSARDNFIRC-UHFFFAOYSA-N
No information available.
Summary of Clinical Use
In 2015, a fixed-dose combination of lumacaftor plus ivacaftor (Orkambi®) was approved (EMA & FDA) for the treatment of cystic fibrosis patients aged 12 years and older carrying the F508del mutation. FDA approval for Orkambi® was expanded in October 2016 to include children with cystic fibrosis aged 6 to 11 who are homozygous for the F508del mutation.
Mechanism Of Action and Pharmacodynamic Effects
VX-809 is reported to correct protein mis-folding in one of the two transmembrane domains of the F508del-CFTR [3]. This effects partial restoration of functional CFTR channels. Combination therapy with compounds with different structure-guided mechanisms by which they correct CFTR function (e.g. Ivacaftor) may provide additional benefit in the treatment of CF [1].