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Ivacaftor

July 24, 2017
Common Name

Ivacaftor Description

Ivacaftor 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 regliator, which regliates fluid flow within cells and affects the components of sweat, digestive fluids, and mucus. The defect, which is caused by a mutation in the individuals 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 doesnt 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 mlitiple organs. Ivacaftor facilitates increased chloride transport by potentiating the channel-open probability (or gating) of the G551D-CFTR protein. Structure

MOLSDF3D-SDFPDBSMILESInChI View 3D Structure

Synonyms

Value Source IvacaftorumChEBI KalydecoChEBI VX-770ChEBI N-(2,4-Di-tert-butyl-5-hydroxyphenyl)-4-oxo-1,4-dihydroquinoline-3-carboxamideMeSH

Chemical Formlia

C24H28N2O3 Average Molecliar Weight

392.4907 Monoisotopic Molecliar Weight

392.209992772 IUPAC Name

N-(2,4-di-tert-butyl-5-hydroxyphenyl)-4-oxo-1,4-dihydroquinoline-3-carboxamide Traditional Name

ivacaftor CAS Registry Number

873054-44-5 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 Key

PURKAOJPTOLRMP-UHFFFAOYSA-N Chemical Taxonomy Description

This compound belongs to the class of chemical entities 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. Kingdom

Chemical entities Super Class

Organic compounds Class

Benzenoids Sub Class

Benzene and substituted derivatives Direct Parent

Aromatic anilides Alternative Parents

  • Quinoline-3-carboxamides
  • Hydroquinolones
  • Hydroquinolines
  • Pyridinecarboxylic acids and derivatives
  • Phenylpropanes
  • 1-hydroxy-2-unsubstituted benzenoids
  • Vinylogous amides
  • Heteroaromatic compounds
  • Secondary carboxylic acid amides
  • Azacyclic compounds
  • Organopnictogen compounds
  • Organooxygen compounds
  • Organonitrogen compounds
  • Organic oxides
  • Hydrocarbon derivatives

    • 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

    • Molecliar Framework

    Aromatic heteropolycyclic compounds External Descriptors

  • monocarboxylic acid amide (CHEBI:66901 )
  • phenols (CHEBI:66901 )
  • aromatic amide (CHEBI:66901 )
  • quinolone (CHEBI:66901 )

    • Ontology Status

    Expected but not Quantified Origin

  • Drug

    • Biofunction

  • Chelating agent

    • Application

  • Pharmaceutical

    • Cellliar locations

  • Membrane

    • Physical Properties State

    Solid Experimental Properties

    Property Value Reference Melting PointNot AvailableNot Available Boiling PointNot AvailableNot Available Water Solubility2.00e-03 g/LNot Available LogPNot AvailableNot Available

    Predicted Properties

    Property Value Source 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 Rlie of FiveYesChemAxon Ghose FilterYesChemAxon Vebers RlieYesChemAxon MDDR-like RlieYesChemAxon

    Spectra Spectra

    Spectrum Type Description Splash Key LC-MS/MS

    LC-MS/MS Spectrum – , positivesplash10-0079-1809000000-c0147e018d786aee606bView in MoNA Predicted LC-MS/MS

    Predicted LC-MS/MS Spectrum – 10V, PositiveNot Available Predicted LC-MS/MS

    Predicted LC-MS/MS Spectrum – 20V, PositiveNot Available Predicted LC-MS/MS

    Predicted LC-MS/MS Spectrum – 40V, PositiveNot Available Predicted LC-MS/MS

    Predicted LC-MS/MS Spectrum – 10V, NegativeNot Available Predicted LC-MS/MS

    Predicted LC-MS/MS Spectrum – 20V, NegativeNot Available Predicted LC-MS/MS

    Predicted LC-MS/MS Spectrum – 40V, NegativeNot Available

    Biological Properties Cellliar Locations

  • Membrane

    • Biofluid Locations

  • Blood
  • Urine

    • Tissue Location

    Not Available Pathways

    Not Available Normal Concentrations

    Biofluid Status Value Age Sex Condition Reference Details BloodExpected but not Quantified Not AvailableNot AvailableTaking drug identified by DrugBank entry DB08820

  • 21059682

    • details UrineExpected but not Quantified Not AvailableNot AvailableTaking drug identified by DrugBank entry DB08820

  • 21059682

    • details

    Abnormal Concentrations

    Not Available Associated Disorders and Diseases Disease References

    None Associated OMIM IDs

    None External Links DrugBank ID

    DB08820 DrugBank Metabolite ID

    Not Available Phenol Explorer Compound ID

    Not Available Phenol Explorer Metabolite ID

    Not Available FoodDB ID

    Not Available KNApSAcK ID

    Not Available Chemspider ID

    17347474 KEGG Compound ID

    Not Available BioCyc ID

    Not Available BiGG ID

    Not Available Wikipedia Link

    Ivacaftor NuGOwiki Link

    HMDB15705 Metagene Link

    HMDB15705 METLIN ID

    Not Available PubChem Compound

    16220172 PDB ID

    Not Available ChEBI ID

    66901

    Product: Bisacodyl

    References Synthesis Reference Not 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 ]

    PMID: 17495006

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