Hmdb loader
Record Information
Version5.0
StatusExpected but not Quantified
Creation Date2012-09-06 15:16:52 UTC
Update Date2022-03-07 02:52:05 UTC
HMDB IDHMDB0015705
Secondary Accession Numbers
  • HMDB15705
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
Data?1582753325
Synonyms
ValueSource
IvacaftorumChEBI
KalydecoChEBI
VX-770ChEBI
N-(2,4-Di-tert-butyl-5-hydroxyphenyl)-4-oxo-1,4-dihydroquinoline-3-carboxamideHMDB
N-(2,4-Bis(1,1-dimethylethyl)-5-hydroxyphenyl)-4-oxo-1,4-dihydroquinoline-3-carboxamideHMDB
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 KeyPURKAOJPTOLRMP-UHFFFAOYSA-N
Chemical Taxonomy
Description Belongs to the class of organic compounds known as aromatic anilides. These are aromatic compounds containing an anilide group in which the carboxamide group is substituted with an aromatic group. They have the general structure RNC(=O)R', where R= benzene, and R = aryl group.
KingdomOrganic compounds
Super ClassBenzenoids
ClassBenzene and substituted derivatives
Sub ClassAnilides
Direct ParentAromatic anilides
Alternative Parents
Substituents
  • Aromatic anilide
  • Quinoline-3-carboxamide
  • Dihydroquinolone
  • Quinoline
  • Dihydroquinoline
  • Phenylpropane
  • Pyridine carboxylic acid or derivatives
  • 1-hydroxy-2-unsubstituted benzenoid
  • Phenol
  • Pyridine
  • Heteroaromatic compound
  • Vinylogous amide
  • Carboxamide group
  • Secondary carboxylic acid amide
  • Azacycle
  • Organoheterocyclic compound
  • Carboxylic acid derivative
  • Organic nitrogen compound
  • Hydrocarbon derivative
  • Organooxygen compound
  • Organonitrogen compound
  • Organic oxide
  • Organopnictogen compound
  • Organic oxygen compound
  • Aromatic heteropolycyclic compound
Molecular FrameworkAromatic heteropolycyclic compounds
External Descriptors
Ontology
Physiological effectNot Available
Disposition
ProcessNot Available
RoleNot Available
Physical Properties
StateSolid
Experimental Molecular Properties
PropertyValueReference
Melting PointNot AvailableNot Available
Boiling PointNot AvailableNot Available
Water Solubility0.002 g/LNot Available
LogPNot AvailableNot Available
Experimental Chromatographic PropertiesNot Available
Predicted Molecular Properties
PropertyValueSource
Water Solubility0.002 g/LALOGPS
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 ŲChemAxon
Rotatable Bond Count4ChemAxon
Refractivity118.68 m³·mol⁻¹ChemAxon
Polarizability43.04 ųChemAxon
Number of Rings3ChemAxon
BioavailabilityYesChemAxon
Rule of FiveNoChemAxon
Ghose FilterNoChemAxon
Veber's RuleNoChemAxon
MDDR-like RuleNoChemAxon
Predicted Chromatographic Properties

Predicted Collision Cross Sections

PredictorAdduct TypeCCS Value (Å2)Reference
DarkChem[M+H]+194.21731661259
DarkChem[M-H]-186.85331661259
DeepCCS[M+H]+203.14330932474
DeepCCS[M-H]-200.78530932474
DeepCCS[M-2H]-234.87630932474
DeepCCS[M+Na]+209.9330932474
AllCCS[M+H]+194.932859911
AllCCS[M+H-H2O]+192.432859911
AllCCS[M+NH4]+197.232859911
AllCCS[M+Na]+197.932859911
AllCCS[M-H]-201.032859911
AllCCS[M+Na-2H]-200.732859911
AllCCS[M+HCOO]-200.532859911

Predicted Kovats Retention Indices

Underivatized

MetaboliteSMILESKovats RI ValueColumn TypeReference
IvacaftorCC(C)(C)C1=CC(=C(O)C=C1NC(=O)C1=CNC2=CC=CC=C2C1=O)C(C)(C)C3868.3Standard polar33892256
IvacaftorCC(C)(C)C1=CC(=C(O)C=C1NC(=O)C1=CNC2=CC=CC=C2C1=O)C(C)(C)C3340.0Standard non polar33892256
IvacaftorCC(C)(C)C1=CC(=C(O)C=C1NC(=O)C1=CNC2=CC=CC=C2C1=O)C(C)(C)C3597.5Semi standard non polar33892256

Derivatized

Derivative Name / StructureSMILESKovats RI ValueColumn TypeReference
Ivacaftor,1TMS,isomer #1CC(C)(C)C1=CC(C(C)(C)C)=C(O[Si](C)(C)C)C=C1NC(=O)C1=C[NH]C2=CC=CC=C2C1=O3522.5Semi standard non polar33892256
Ivacaftor,1TMS,isomer #2CC(C)(C)C1=CC(C(C)(C)C)=C(N(C(=O)C2=C[NH]C3=CC=CC=C3C2=O)[Si](C)(C)C)C=C1O3261.1Semi standard non polar33892256
Ivacaftor,1TMS,isomer #3CC(C)(C)C1=CC(C(C)(C)C)=C(NC(=O)C2=CN([Si](C)(C)C)C3=CC=CC=C3C2=O)C=C1O3492.3Semi standard non polar33892256
Ivacaftor,2TMS,isomer #1CC(C)(C)C1=CC(C(C)(C)C)=C(N(C(=O)C2=C[NH]C3=CC=CC=C3C2=O)[Si](C)(C)C)C=C1O[Si](C)(C)C3230.7Semi standard non polar33892256
Ivacaftor,2TMS,isomer #1CC(C)(C)C1=CC(C(C)(C)C)=C(N(C(=O)C2=C[NH]C3=CC=CC=C3C2=O)[Si](C)(C)C)C=C1O[Si](C)(C)C3291.2Standard non polar33892256
Ivacaftor,2TMS,isomer #1CC(C)(C)C1=CC(C(C)(C)C)=C(N(C(=O)C2=C[NH]C3=CC=CC=C3C2=O)[Si](C)(C)C)C=C1O[Si](C)(C)C3481.6Standard polar33892256
Ivacaftor,2TMS,isomer #2CC(C)(C)C1=CC(C(C)(C)C)=C(O[Si](C)(C)C)C=C1NC(=O)C1=CN([Si](C)(C)C)C2=CC=CC=C2C1=O3549.1Semi standard non polar33892256
Ivacaftor,2TMS,isomer #2CC(C)(C)C1=CC(C(C)(C)C)=C(O[Si](C)(C)C)C=C1NC(=O)C1=CN([Si](C)(C)C)C2=CC=CC=C2C1=O3316.6Standard non polar33892256
Ivacaftor,2TMS,isomer #2CC(C)(C)C1=CC(C(C)(C)C)=C(O[Si](C)(C)C)C=C1NC(=O)C1=CN([Si](C)(C)C)C2=CC=CC=C2C1=O3563.5Standard polar33892256
Ivacaftor,2TMS,isomer #3CC(C)(C)C1=CC(C(C)(C)C)=C(N(C(=O)C2=CN([Si](C)(C)C)C3=CC=CC=C3C2=O)[Si](C)(C)C)C=C1O3299.0Semi standard non polar33892256
Ivacaftor,2TMS,isomer #3CC(C)(C)C1=CC(C(C)(C)C)=C(N(C(=O)C2=CN([Si](C)(C)C)C3=CC=CC=C3C2=O)[Si](C)(C)C)C=C1O3336.5Standard non polar33892256
Ivacaftor,2TMS,isomer #3CC(C)(C)C1=CC(C(C)(C)C)=C(N(C(=O)C2=CN([Si](C)(C)C)C3=CC=CC=C3C2=O)[Si](C)(C)C)C=C1O3520.1Standard polar33892256
Ivacaftor,3TMS,isomer #1CC(C)(C)C1=CC(C(C)(C)C)=C(N(C(=O)C2=CN([Si](C)(C)C)C3=CC=CC=C3C2=O)[Si](C)(C)C)C=C1O[Si](C)(C)C3310.7Semi standard non polar33892256
Ivacaftor,3TMS,isomer #1CC(C)(C)C1=CC(C(C)(C)C)=C(N(C(=O)C2=CN([Si](C)(C)C)C3=CC=CC=C3C2=O)[Si](C)(C)C)C=C1O[Si](C)(C)C3334.4Standard non polar33892256
Ivacaftor,3TMS,isomer #1CC(C)(C)C1=CC(C(C)(C)C)=C(N(C(=O)C2=CN([Si](C)(C)C)C3=CC=CC=C3C2=O)[Si](C)(C)C)C=C1O[Si](C)(C)C3394.0Standard polar33892256
Ivacaftor,1TBDMS,isomer #1CC(C)(C)C1=CC(C(C)(C)C)=C(O[Si](C)(C)C(C)(C)C)C=C1NC(=O)C1=C[NH]C2=CC=CC=C2C1=O3718.3Semi standard non polar33892256
Ivacaftor,1TBDMS,isomer #2CC(C)(C)C1=CC(C(C)(C)C)=C(N(C(=O)C2=C[NH]C3=CC=CC=C3C2=O)[Si](C)(C)C(C)(C)C)C=C1O3521.0Semi standard non polar33892256
Ivacaftor,1TBDMS,isomer #3CC(C)(C)C1=CC(C(C)(C)C)=C(NC(=O)C2=CN([Si](C)(C)C(C)(C)C)C3=CC=CC=C3C2=O)C=C1O3710.5Semi standard non polar33892256
Ivacaftor,2TBDMS,isomer #1CC(C)(C)C1=CC(C(C)(C)C)=C(N(C(=O)C2=C[NH]C3=CC=CC=C3C2=O)[Si](C)(C)C(C)(C)C)C=C1O[Si](C)(C)C(C)(C)C3681.9Semi standard non polar33892256
Ivacaftor,2TBDMS,isomer #1CC(C)(C)C1=CC(C(C)(C)C)=C(N(C(=O)C2=C[NH]C3=CC=CC=C3C2=O)[Si](C)(C)C(C)(C)C)C=C1O[Si](C)(C)C(C)(C)C3635.9Standard non polar33892256
Ivacaftor,2TBDMS,isomer #1CC(C)(C)C1=CC(C(C)(C)C)=C(N(C(=O)C2=C[NH]C3=CC=CC=C3C2=O)[Si](C)(C)C(C)(C)C)C=C1O[Si](C)(C)C(C)(C)C3667.8Standard polar33892256
Ivacaftor,2TBDMS,isomer #2CC(C)(C)C1=CC(C(C)(C)C)=C(O[Si](C)(C)C(C)(C)C)C=C1NC(=O)C1=CN([Si](C)(C)C(C)(C)C)C2=CC=CC=C2C1=O3909.9Semi standard non polar33892256
Ivacaftor,2TBDMS,isomer #2CC(C)(C)C1=CC(C(C)(C)C)=C(O[Si](C)(C)C(C)(C)C)C=C1NC(=O)C1=CN([Si](C)(C)C(C)(C)C)C2=CC=CC=C2C1=O3660.3Standard non polar33892256
Ivacaftor,2TBDMS,isomer #2CC(C)(C)C1=CC(C(C)(C)C)=C(O[Si](C)(C)C(C)(C)C)C=C1NC(=O)C1=CN([Si](C)(C)C(C)(C)C)C2=CC=CC=C2C1=O3731.6Standard polar33892256
Ivacaftor,2TBDMS,isomer #3CC(C)(C)C1=CC(C(C)(C)C)=C(N(C(=O)C2=CN([Si](C)(C)C(C)(C)C)C3=CC=CC=C3C2=O)[Si](C)(C)C(C)(C)C)C=C1O3706.6Semi standard non polar33892256
Ivacaftor,2TBDMS,isomer #3CC(C)(C)C1=CC(C(C)(C)C)=C(N(C(=O)C2=CN([Si](C)(C)C(C)(C)C)C3=CC=CC=C3C2=O)[Si](C)(C)C(C)(C)C)C=C1O3649.8Standard non polar33892256
Ivacaftor,2TBDMS,isomer #3CC(C)(C)C1=CC(C(C)(C)C)=C(N(C(=O)C2=CN([Si](C)(C)C(C)(C)C)C3=CC=CC=C3C2=O)[Si](C)(C)C(C)(C)C)C=C1O3689.3Standard polar33892256
Ivacaftor,3TBDMS,isomer #1CC(C)(C)C1=CC(C(C)(C)C)=C(N(C(=O)C2=CN([Si](C)(C)C(C)(C)C)C3=CC=CC=C3C2=O)[Si](C)(C)C(C)(C)C)C=C1O[Si](C)(C)C(C)(C)C3891.2Semi standard non polar33892256
Ivacaftor,3TBDMS,isomer #1CC(C)(C)C1=CC(C(C)(C)C)=C(N(C(=O)C2=CN([Si](C)(C)C(C)(C)C)C3=CC=CC=C3C2=O)[Si](C)(C)C(C)(C)C)C=C1O[Si](C)(C)C(C)(C)C3808.9Standard non polar33892256
Ivacaftor,3TBDMS,isomer #1CC(C)(C)C1=CC(C(C)(C)C)=C(N(C(=O)C2=CN([Si](C)(C)C(C)(C)C)C3=CC=CC=C3C2=O)[Si](C)(C)C(C)(C)C)C=C1O[Si](C)(C)C(C)(C)C3634.8Standard polar33892256
Spectra

GC-MS Spectra

Spectrum TypeDescriptionSplash KeyDeposition DateSourceView
Predicted GC-MSPredicted GC-MS Spectrum - Ivacaftor GC-MS (Non-derivatized) - 70eV, Positivesplash10-00di-0739000000-1b41f2c7ddedd90d43c82017-09-01Wishart LabView Spectrum
Predicted GC-MSPredicted GC-MS Spectrum - Ivacaftor GC-MS (1 TMS) - 70eV, Positivesplash10-006y-3351900000-dc90833dbef87cc492c02017-10-06Wishart LabView Spectrum
Predicted GC-MSPredicted GC-MS Spectrum - Ivacaftor GC-MS (Non-derivatized) - 70eV, PositiveNot Available2021-10-12Wishart LabView Spectrum
Predicted GC-MSPredicted GC-MS Spectrum - Ivacaftor GC-MS (Non-derivatized) - 70eV, PositiveNot Available2021-10-12Wishart LabView Spectrum

MS/MS Spectra

Spectrum TypeDescriptionSplash KeyDeposition DateSourceView
Experimental LC-MS/MSLC-MS/MS Spectrum - Ivacaftor LC-ESI-qTof , Positive-QTOFsplash10-03gj-1891400000-9f74f1c76f8bde03b2862017-09-14HMDB team, MONAView Spectrum
Experimental LC-MS/MSLC-MS/MS Spectrum - Ivacaftor , positive-QTOFsplash10-0079-1809000000-c0147e018d786aee606b2017-09-14HMDB team, MONAView Spectrum
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - Ivacaftor 10V, Positive-QTOFsplash10-0006-0009000000-86c4c1172d1bee0ab8cf2016-08-03Wishart LabView Spectrum
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - Ivacaftor 20V, Positive-QTOFsplash10-00dl-0918000000-00798a3656e171f62c812016-08-03Wishart LabView Spectrum
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - Ivacaftor 40V, Positive-QTOFsplash10-0006-0911000000-2fefa753407d0181cec32016-08-03Wishart LabView Spectrum
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - Ivacaftor 10V, Negative-QTOFsplash10-0006-0409000000-9aa079aa9d35e2f8ab132016-08-03Wishart LabView Spectrum
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - Ivacaftor 20V, Negative-QTOFsplash10-0006-0900000000-30095278d7b7875589bf2016-08-03Wishart LabView Spectrum
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - Ivacaftor 40V, Negative-QTOFsplash10-0006-0900000000-fc85de7523217af66c4c2016-08-03Wishart LabView Spectrum
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - Ivacaftor 10V, Positive-QTOFsplash10-0079-0509000000-16aa918207aec379d6152021-10-11Wishart LabView Spectrum
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - Ivacaftor 20V, Positive-QTOFsplash10-00di-0900000000-383766b2b3690775474c2021-10-11Wishart LabView Spectrum
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - Ivacaftor 40V, Positive-QTOFsplash10-0ck9-2619000000-2307c51d7b28f4ff118f2021-10-11Wishart LabView Spectrum
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - Ivacaftor 10V, Negative-QTOFsplash10-0006-0009000000-d21896041c7a6bff6e472021-10-12Wishart LabView Spectrum
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - Ivacaftor 20V, Negative-QTOFsplash10-0006-0309000000-696199233265215e456f2021-10-12Wishart LabView Spectrum
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - Ivacaftor 40V, Negative-QTOFsplash10-0006-1913000000-a31f02ed83400d9b16dd2021-10-12Wishart LabView Spectrum
Biological Properties
Cellular Locations
  • Membrane
Biospecimen Locations
  • Blood
  • Urine
Tissue LocationsNot Available
Pathways
Normal Concentrations
BiospecimenStatusValueAgeSexConditionReferenceDetails
BloodExpected but not QuantifiedNot QuantifiedNot AvailableNot AvailableTaking drug identified by DrugBank entry DB08820 details
UrineExpected but not QuantifiedNot QuantifiedNot AvailableNot AvailableTaking drug identified by DrugBank entry DB08820 details
Abnormal Concentrations
Not Available
Associated Disorders and Diseases
Disease ReferencesNone
Associated OMIM IDsNone
DrugBank IDDB08820
Phenol Explorer Compound IDNot Available
FooDB IDNot Available
KNApSAcK IDNot Available
Chemspider ID17347474
KEGG Compound IDNot Available
BioCyc IDNot Available
BiGG IDNot Available
Wikipedia LinkIvacaftor
METLIN IDNot Available
PubChem Compound16220172
PDB IDNot Available
ChEBI ID66901
Food Biomarker OntologyNot Available
VMH IDNot Available
MarkerDB IDNot Available
Good Scents IDNot Available
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. [PubMed: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. [PubMed: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. doi: 10.1016/j.jcf.2011.12.005. Epub 2012 Jan 30. [PubMed:22293084 ]