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Record Information
Version3.6
Creation Date2012-09-06 15:16:52 UTC
Update Date2016-02-11 01:34:05 UTC
HMDB IDHMDB15705
Secondary Accession NumbersNone
Metabolite Identification
Common NameIvacaftor
DescriptionIvacaftor is only found in individuals that have used or taken this drug. It is a drug for the treatment of cystic fibrosis, developed by Vertex Pharmaceuticals and 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. One mutation, G551D, lets the CFTR protein reach the epithelial cell surface, but doesn't let it transport chloride through the ion channel. Ivacaftor is a potentiator of the CFTR protein. The CFTR protein is a chloride channel present at the surface of epithelial cells in multiple organs. Ivacaftor facilitates increased chloride transport by potentiating the channel-open probability (or gating) of the G551D-CFTR protein.
Structure
Thumb
Synonyms
ValueSource
IvacaftorumChEBI
KalydecoChEBI
VX-770ChEBI
Chemical FormulaC24H28N2O3
Average Molecular Weight392.4907
Monoisotopic Molecular Weight392.209992772
IUPAC NameN-(2,4-di-tert-butyl-5-hydroxyphenyl)-4-oxo-1,4-dihydroquinoline-3-carboxamide
Traditional Nameivacaftor
CAS Registry Number873054-44-5
SMILES
CC(C)(C)C1=CC(=C(O)C=C1NC(=O)C1=CNC2=CC=CC=C2C1=O)C(C)(C)C
InChI Identifier
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)
InChI KeyInChIKey=PURKAOJPTOLRMP-UHFFFAOYSA-N
Chemical Taxonomy
DescriptionThis compound belongs to the class of organic compounds known as quinoline-3-carboxamides. These are quinolines in which the quinoline ring system is substituted by one carboxamide group at the 3-position.
KingdomOrganic compounds
Super ClassOrganoheterocyclic compounds
ClassQuinolines and derivatives
Sub ClassQuinoline carboxamides
Direct ParentQuinoline-3-carboxamides
Alternative Parents
Substituents
  • Quinoline-3-carboxamide
  • Dihydroquinolone
  • N-arylamide
  • Dihydroquinoline
  • Pyridine carboxylic acid or derivatives
  • Phenylpropane
  • Phenol
  • Benzenoid
  • Pyridine
  • Monocyclic benzene moiety
  • Heteroaromatic compound
  • Vinylogous amide
  • Secondary carboxylic acid amide
  • Carboxamide group
  • Azacycle
  • Carboxylic acid derivative
  • Hydrocarbon derivative
  • Organooxygen compound
  • Organonitrogen compound
  • Carbonyl group
  • Aromatic heteropolycyclic compound
Molecular FrameworkAromatic heteropolycyclic compounds
External Descriptors
Ontology
StatusExpected but not Quantified
Origin
  • Drug
Biofunction
  • Chelating agent
Application
  • Pharmaceutical
Cellular locations
  • Membrane
Physical Properties
StateSolid
Experimental Properties
PropertyValueReference
Melting PointNot AvailableNot Available
Boiling PointNot AvailableNot Available
Water Solubility2.00e-03 g/LNot Available
LogPNot AvailableNot Available
Predicted Properties
PropertyValueSource
Water Solubility0.002 mg/mLALOGPS
logP5ALOGPS
logP5.76ChemAxon
logS-5.3ALOGPS
pKa (Strongest Acidic)6.57ChemAxon
pKa (Strongest Basic)-0.95ChemAxon
Physiological Charge-1ChemAxon
Hydrogen Acceptor Count4ChemAxon
Hydrogen Donor Count3ChemAxon
Polar Surface Area78.43 Å2ChemAxon
Rotatable Bond Count4ChemAxon
Refractivity118.68 m3·mol-1ChemAxon
Polarizability43.04 Å3ChemAxon
Number of Rings3ChemAxon
Bioavailability1ChemAxon
Rule of FiveYesChemAxon
Ghose FilterYesChemAxon
Veber's RuleYesChemAxon
MDDR-like RuleYesChemAxon
Spectra
Spectra
Spectrum TypeDescriptionSplash Key
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 10V, PositiveNot Available
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 20V, PositiveNot Available
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 40V, PositiveNot Available
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 10V, NegativeNot Available
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 20V, NegativeNot Available
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 40V, NegativeNot Available
Biological Properties
Cellular Locations
  • Membrane
Biofluid Locations
  • Blood
  • Urine
Tissue LocationNot Available
PathwaysNot Available
Normal Concentrations
BiofluidStatusValueAgeSexConditionReferenceDetails
BloodExpected but not QuantifiedNot ApplicableNot AvailableNot AvailableTaking drug identified by DrugBank entry DB08820
  • Not Applicable
details
UrineExpected but not QuantifiedNot ApplicableNot AvailableNot AvailableTaking drug identified by DrugBank entry DB08820
  • Not Applicable
details
Abnormal Concentrations
Not Available
Associated Disorders and Diseases
Disease ReferencesNone
Associated OMIM IDsNone
DrugBank IDDB08820
DrugBank Metabolite IDNot Available
Phenol Explorer Compound IDNot Available
Phenol Explorer Metabolite IDNot Available
FoodDB IDNot Available
KNApSAcK IDNot Available
Chemspider ID17347474
KEGG Compound IDNot Available
BioCyc IDNot Available
BiGG IDNot Available
Wikipedia LinkIvacaftor
NuGOwiki LinkHMDB15705
Metagene LinkHMDB15705
METLIN IDNot Available
PubChem Compound16220172
PDB IDNot Available
ChEBI ID66901
References
Synthesis ReferenceNot Available
Material Safety Data Sheet (MSDS)Not Available
General References
  1. 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, Ordonez 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. doi: 10.1056/NEJMoa0909825. [21083385 ]
  2. Ramsey BW, Davies J, McElvaney NG, Tullis E, Bell SC, Drevinek P, Griese M, McKone EF, Wainwright CE, Konstan MW, Moss R, Ratjen F, Sermet-Gaudelus I, Rowe SM, Dong Q, Rodriguez S, Yen K, Ordonez C, Elborn JS: A CFTR potentiator in patients with cystic fibrosis and the G551D mutation. N Engl J Med. 2011 Nov 3;365(18):1663-72. doi: 10.1056/NEJMoa1105185. [22047557 ]

Enzymes

General function:
Involved in monooxygenase activity
Specific function:
Cytochromes P450 are a group of heme-thiolate monooxygenases. In liver microsomes, this enzyme is involved in an NADPH-dependent electron transport pathway. It performs a variety of oxidation reactions (e.g. caffeine 8-oxidation, omeprazole sulphoxidation, midazolam 1'-hydroxylation and midazolam 4-hydroxylation) of structurally unrelated compounds, including steroids, fatty acids, and xenobiotics. Acts as a 1,8-cineole 2-exo-monooxygenase. The enzyme also hydroxylates etoposide.
Gene Name:
CYP3A4
Uniprot ID:
P08684
Molecular weight:
57255.585
General function:
Involved in ATP binding
Specific function:
Involved in the transport of chloride ions. May regulate bicarbonate secretion and salvage in epithelial cells by regulating the SLC4A7 transporter. Can inhibit the chloride channel activity of ANO1.
Gene Name:
CFTR
Uniprot ID:
P13569
Molecular weight:
168139.895
References
  1. Yu H, Burton B, Huang CJ, Worley J, Cao D, Johnson JP Jr, Urrutia A, Joubran J, Seepersaud S, Sussky K, Hoffman BJ, Van Goor F: Ivacaftor potentiation of multiple CFTR channels with gating mutations. J Cyst Fibros. 2012 May;11(3):237-45. Epub 2012 Jan 30. [22293084 ]