ivacaftor   Click here for help

GtoPdb Ligand ID: 4342

Synonyms: Kalydeco® | VX-770
Approved drug PDB Ligand
ivacaftor is an approved drug (FDA and EMA (2012))
Compound class: Synthetic organic
Comment: Ivacaftor is a cystic fibrosis transmembrane conductance regulator (CFTR) potentiator, the net effect of which is increased chloride channel opening.
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2D Structure
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Physico-chemical Properties
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Hydrogen bond acceptors 3
Hydrogen bond donors 3
Rotatable bonds 5
Topological polar surface area 82.19
Molecular weight 392.21
XLogP 6.93
No. Lipinski's rules broken 1
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Canonical SMILES O=C(c1c[nH]c2c(c1=O)cccc2)Nc1cc(O)c(cc1C(C)(C)C)C(C)(C)C
Isomeric SMILES O=C(c1c[nH]c2c(c1=O)cccc2)Nc1cc(O)c(cc1C(C)(C)C)C(C)(C)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)
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Summary of Clinical Use Click here for help
This drug was originally approved for use in cystic fibrosis patients carrying the G551D CFTR gating mutation. Prior to full approval in 2012, the EMA had designated ivacaftor as an orphan medicine for rare diseases in 2008. In December 2014, FDA approval was expanded to include patients with CFTR mutations, including R117H. In late March 2015, FDA approval was expanded to include the treatment of children aged 2-5 carrying any one of 10 different CFTR mutations (G551D, G1244E, G1349D, G178R, G551S, S1251N, S1255P, S549N, S549R and R117H).
In July 2015, a fixed-dose combination of ivacaftor plus lumacaftor (Orkambi®) was approved by the US 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. In May 2017, use of ivacaftor was approved for use in a number of rare and previously excluded CFTR mutations, bringing the total number of mutations covered to 33.
Mechanism Of Action and Pharmacodynamic Effects Click here for help
Ivacaftor is a channel potentiator type drug [1-2]. It has been designed to increase the time that activated CFTR channels remain open, thus restoring Cl- transport. This action partially normalises the consistency of mucous and digestive juices in cystic fibrosis patients, and relieves disease symptoms.
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