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Icatibant

July 24, 2017
Common Name

Icatibant Description

Icatibant (Firazyr) is a peptidomimetic drug consisting of ten amino acids, which is an effective and specific antagonist of bradykinin B2 receptors. It has been approved in the EU for use in hereditary angioedema, and is under investigation for a number of other conditions in which bradykinin is thought to play a significant role. Icatibant currently has orphan drug status in the United States. Structure

MOLSDFPDBSMILESInChI

Synonyms

Value Source JE049HMDB D-Arg(hyp(3)-thi(5)-D-tic(7)-oic(8))BKMeSH HOE 140MeSH HOE-140MeSH Hoechst 140MeSH Hoechst-140MeSH Icatibant acetateMeSH

Chemical Formlia

C59H89N19O13S Average Molecliar Weight

1304.522 Monoisotopic Molecliar Weight

1303.660794719 IUPAC Name

(2S)-2-{[(3aS,7aS)-1-{2-[(2S)-2-[(2S)-2-(2-{[(4R)-1-(1-{2-[(2R)-2-amino-5-[(diaminomethylidene)amino]pentanamido]-5-[(diaminomethylidene)amino]pentanoyl}pyrrolidine-2-carbonyl)-4-hydroxypyrrolidin-2-yl]formamido}acetamido)-3-(thiophen-2-yl)propanamido]-3-hydroxypropanoyl]-1,2,3,4-tetrahydroisoquinoline-3-carbonyl}-octahydro-1H-indol-2-yl]formamido}-5-[(diaminomethylidene)amino]pentanoic acid Traditional Name

icatibant CAS Registry Number

130308-48-4 SMILES

[H][C@]12CC(N(C(=O)C3CC4=CC=CC=C4CN3C(=O)[C@H](CO)NC(=O)[C@H](CC3=CC=CS3)NC(=O)CNC(=O)C3C[C@@H](O)CN3C(=O)C3CCCN3C(=O)C(CCCN=C(N)N)NC(=O)[C@H](N)CCCN=C(N)N)[C@@]1([H])CCCC2)C(=O)N[C@@H](CCCN=C(N)N)C(O)=O

InChI Identifier

InChI=1S/C59H89N19O13S/c60-37(14-5-19-67-57(61)62)48(82)72-38(15-6-20-68-58(63)64)52(86)75-22-8-18-43(75)54(88)77-30-35(80)26-44(77)50(84)70-28-47(81)71-40(27-36-13-9-23-92-36)49(83)74-41(31-79)53(87)76-29-34-12-2-1-10-32(34)24-46(76)55(89)78-42-17-4-3-11-33(42)25-45(78)51(85)73-39(56(90)91)16-7-21-69-59(65)66/h1-2,9-10,12-13,23,33,35,37-46,79-80H,3-8,11,14-22,24-31,60H2,(H,70,84)(H,71,81)(H,72,82)(H,73,85)(H,74,83)(H,90,91)(H4,61,62,67)(H4,63,64,68)(H4,65,66,69)/t33-,35+,37+,38?,39-,40-,41-,42-,43?,44?,45?,46?/m0/s1

InChI Key

QURWXBZNHXJZBE-MCDGZUPGSA-N Chemical Taxonomy Description

This compound belongs to the class of chemical entities known as oligopeptides. These are organic compounds containing a sequence of between three and ten alpha-amino acids joined by peptide bonds. Kingdom

Chemical entities Super Class

Organic compounds Class

Organic acids and derivatives Sub Class

Carboxylic acids and derivatives Direct Parent

Oligopeptides Alternative Parents

  • N-acyl-L-alpha-amino acids
  • Proline and derivatives
  • Alpha amino acid amides
  • Tetrahydroisoquinolines
  • Indoles and derivatives
  • N-acylpyrrolidines
  • Pyrrolidinecarboxamides
  • Benzenoids
  • N-acyl amines
  • Thiophenes
  • Tertiary carboxylic acid amides
  • Heteroaromatic compounds
  • Secondary alcohols
  • Secondary carboxylic acid amides
  • Amino acids
  • Guanidines
  • Propargyl-type 1,3-dipolar organic compounds
  • Azacyclic compounds
  • Monocarboxylic acids and derivatives
  • Carboximidamides
  • Carboxylic acids
  • Hydrocarbon derivatives
  • Carbonyl compounds
  • Monoalkylamines
  • Organic oxides
  • Primary alcohols
  • Organopnictogen compounds

    • Substituents

  • Alpha-oligopeptide
  • Proline or derivatives
  • N-acyl-alpha-amino acid
  • N-acyl-alpha amino acid or derivatives
  • N-acyl-l-alpha-amino acid
  • Alpha-amino acid amide
  • N-substituted-alpha-amino acid
  • Alpha-amino acid or derivatives
  • Tetrahydroisoquinoline
  • Indole or derivatives
  • N-acylpyrrolidine
  • Pyrrolidine carboxylic acid or derivatives
  • Pyrrolidine-2-carboxamide
  • Fatty acyl
  • Fatty amide
  • Benzenoid
  • N-acyl-amine
  • Thiophene
  • Heteroaromatic compound
  • Tertiary carboxylic acid amide
  • Pyrrolidine
  • Amino acid or derivatives
  • Carboxamide group
  • Guanidine
  • Amino acid
  • Secondary carboxylic acid amide
  • Secondary alcohol
  • Azacycle
  • Organic 1,3-dipolar compound
  • Carboxylic acid
  • Propargyl-type 1,3-dipolar organic compound
  • Organoheterocyclic compound
  • Monocarboxylic acid or derivatives
  • Carboximidamide
  • Primary aliphatic amine
  • Organic oxide
  • Primary amine
  • Organic nitrogen compound
  • Organic oxygen compound
  • Amine
  • Carbonyl group
  • Primary alcohol
  • Organopnictogen compound
  • Hydrocarbon derivative
  • Alcohol
  • Organonitrogen compound
  • Organooxygen compound
  • Aromatic heteropolycyclic compound

    • Molecliar Framework

    Aromatic heteropolycyclic compounds External Descriptors

    Not Available Ontology Status

    Expected but not Quantified Origin

  • Drug

    • Biofunction

  • Adrenergic beta-Antagonists

    • Application

  • Pharmaceutical

    • Cellliar locations

  • Cytoplasm
  • Membrane

    • Physical Properties State

    Solid Experimental Properties

    Property Value Reference Melting PointNot AvailableNot Available Boiling PointNot AvailableNot Available Water Solubility5.70e-02 g/LNot Available LogPNot AvailableNot Available

    Predicted Properties

    Property Value Source Water Solubility0.057 mg/mLALOGPS logP-2.3ALOGPS logP-8ChemAxon logS-4.4ALOGPS pKa (Strongest Acidic)3.46ChemAxon pKa (Strongest Basic)11.45ChemAxon Physiological Charge3ChemAxon Hydrogen Acceptor Count23ChemAxon Hydrogen Donor Count15ChemAxon Polar Surface Area523.72 Å2ChemAxon Rotatable Bond Count30ChemAxon Refractivity332.91 m3·mol-1ChemAxon Polarizability137.03 Å3ChemAxon Number of Rings7ChemAxon Bioavailability0ChemAxon Rlie of FiveYesChemAxon Ghose FilterYesChemAxon Vebers RlieYesChemAxon MDDR-like RlieYesChemAxon

    Spectra Spectra

    Spectrum Type Description Splash Key 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

  • Cytoplasm
  • 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 DB06196

  • 21059682

    • details UrineExpected but not Quantified Not AvailableNot AvailableTaking drug identified by DrugBank entry DB06196

  • 21059682

    • details

    Abnormal Concentrations

    Not Available Associated Disorders and Diseases Disease References

    None Associated OMIM IDs

    None External Links DrugBank ID

    DB06196 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

    64461 KEGG Compound ID

    Not Available BioCyc ID

    Not Available BiGG ID

    Not Available Wikipedia Link

    Icatibant NuGOwiki Link

    HMDB15624 Metagene Link

    HMDB15624 METLIN ID

    Not Available PubChem Compound

    71364 PDB ID

    Not Available ChEBI ID

    Not Available

    Product: Nadifloxacin

    References Synthesis Reference Not Available Material Safety Data Sheet (MSDS) Not Available General References
    1. Cockcroft JR, Chowienczyk PJ, Brett SE, Bender N, Ritter JM: Inhibition of bradykinin-induced vasodilation in human forearm vasculature by icatibant, a potent B2-receptor antagonist. Br J Clin Pharmacol. 1994 Oct;38(4):317-21. [PubMed:7833220 ]
    2. Bork K, Frank J, Grundt B, Schlattmann P, Nussberger J, Kreuz W: Treatment of acute edema attacks in hereditary angioedema with a bradykinin receptor-2 antagonist (Icatibant). J Allergy Clin Immunol. 2007 Jun;119(6):1497-503. Epub 2007 Apr 5. [PubMed:17418383 ]

    Enzymes

    General function:
    Involved in proteolysis
    Specific function:
    Broad specificity aminopeptidase. Plays a role in the final digestion of peptides generated from hydrolysis of proteins by gastric and pancreatic proteases. May play a critical role in the pathogenesis of cholesterol gallstone disease. May be involved in the metabolism of regulatory peptides of diverse cell types, responsible for the processing of peptide hormones, such as angiotensin III and IV, neuropeptides, and chemokines. Found to cleave antigen peptides bound to major histocompatibility complex class II molecules of presenting cells and to degrade neurotransmitters at synaptic junctions. Is also implicated as a regulator of IL-8 bioavailability in the endometrium, and therefore may contribute to the regulation of angiogenesis. Is used as a marker for acute myeloid leukemia and plays a role in tumor invasion. In case of human coronavirus 229E (HCoV-229E) infection, serves as receptor for HCoV-229E spike glycoprotein. Mediates as well human cytomegalovirus (HCMV) infection.
    Gene Name:
    ANPEP
    Uniprot ID:
    P15144
    Molecular weight:
    Not Available
    References
    1. Bawolak MT, Fortin JP, Vogel LK, Adam A, Marceau F: The bradykinin B2 receptor antagonist icatibant (Hoe 140) blocks aminopeptidase N at micromolar concentrations: off-target alterations of signaling mediated by the bradykinin B1 and angiotensin receptors. Eur J Pharmacol. 2006 Dec 3;551(1-3):108-11. Epub 2006 Sep 8. [PubMed:17026984 ]
    General function:
    Involved in G-protein coupled receptor protein signaling pathway
    Specific function:
    Receptor for bradykinin. It is associated with G proteins that activate a phosphatidylinositol-calcium second messenger system
    Gene Name:
    BDKRB2
    Uniprot ID:
    P30411
    Molecular weight:
    44460.2
    References
    1. Privitera PJ, Beckstead RM, Yates P, Walgren R: Autoradiographic localization of [125I-Tyr0]bradykinin binding sites in brains of Wistar-Kyoto and spontaneously hypertensive rats. Cell Mol Neurobiol. 2003 Oct;23(4-5):805-15. [PubMed:14514033 ]
    2. Chen X, Ji ZL, Chen YZ: TTD: Therapeutic Target Database. Nucleic Acids Res. 2002 Jan 1;30(1):412-5. [PubMed:11752352 ]

    PMID: 17585751

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