icatibant   Click here for help

GtoPdb Ligand ID: 667

Synonyms: D-Arg-[Hyp3,Thi5,D-Tic7,Oic8]BK | Firazyr® | HOE 140 | HOE140
Approved drug Immunopharmacology Ligand
icatibant is an approved drug (EMA (2008), FDA (2011))
Compound class: Peptide
Comment: Synthetic analogue of bradykinin. There is some ambiguity in the literature and on online resources as to the exact chemical structure and stereochemistry of icatibant.
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Ligand Activity Visualisation Charts

These are box plot that provide a unique visualisation, summarising all the activity data for a ligand taken from ChEMBL and GtoPdb across multiple targets and species. Click on a plot to see the median, interquartile range, low and high data points. A value of zero indicates that no data are available. A separate chart is created for each target, and where possible the algorithm tries to merge ChEMBL and GtoPdb targets by matching them on name and UniProt accession, for each available species. However, please note that inconsistency in naming of targets may lead to data for the same target being reported across multiple charts.

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View interactive charts of activity data across species
2D Structure
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2D Structure

An image of the ligand's 2D structure. For small molecules with SMILES these are drawn using the NCI/CADD Chemical Identifier Resolver. Click on the image to access the chemical structure search tool with the ligand pre-loaded in the structure editor. For other types of ligands, e.g. longer nucleotides and peptides, a manually drawn representation of the molecule may be provided.

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SMILES / InChI / InChIKey
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SMILES / InChI / InChIKey

SMILES (Simplified Molecular Input Line Entry Specification) A specification for unambiguously describing the structure of chemical molecules using short ASCII strings. Canonical SMILES specify a unique representation of the 2D structure without chiral or isotopic specifications. Isomeric SMILES include chiral specification and isotopes.

Standard InChI (IUPAC International Chemical Identifier) and InChIKey InChI is a non-proprietary, standard, textual identifier for chemical substances designed to facilitate linking of information and database searching. An InChIKey is a simplified version of a full InChI, designed for easier web searching.

Generated using the Chemistry Development Kit (CDK) (Willighagen EL et al. Journal of Cheminformatics vol. 9:33. 2017, doi:10.1186/s13321-017-0220-4; https://cdk.github.io/)

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Canonical SMILES OC[C@@H](C(=O)N1Cc2ccccc2CC1C(=O)N1[C@H]2CCCC[C@H]2CC1C(=O)N[C@H](C(=O)O)CCCN=C(N)N)NC(=O)[C@H](Cc1cccs1)NC(=O)CNC(=O)C1C[C@H](CN1C(=O)C1CCCN1C(=O)C(NC(=O)[C@@H](CCCN=C(N)N)N)CCCN=C(N)N)O
Isomeric SMILES OC[C@@H](C(=O)N1Cc2ccccc2CC1C(=O)N1[C@H]2CCCC[C@H]2CC1C(=O)N[C@H](C(=O)O)CCCN=C(N)N)NC(=O)[C@H](Cc1cccs1)NC(=O)CNC(=O)C1C[C@H](CN1C(=O)C1CCCN1C(=O)C(NC(=O)[C@@H](CCCN=C(N)N)N)CCCN=C(N)N)O
InChI 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

Generated using the Chemistry Development Kit (CDK) (Willighagen EL et al. Journal of Cheminformatics vol. 9:33. 2017, doi:10.1186/s13321-017-0220-4; https://cdk.github.io/)
No information available.
Summary of Clinical Use Click here for help
Icatibant has been approved to treat hereditary angiodema (HAE). The drug is under investigation for other conditions susceptible to bradykinin amelioration eg ACE inhibitor-induced angiodema, knee ostoearthritis and use during cardiopulmonary bypass surgery. Click here to link to Clinicaltrials.gov's records for this drug.

COVID-19: Elevated levels of bradykinin have been detected in COVID-19 patients, and it is proposed that this 'bradykinin storm' might underlie many of the highly damaging symptoms of the infection [2,7,12]. By antagonising bradykinin signalling icatibant provides an exisitng therapeutic option to reduce the multi-system effects of bradykinin [13]. Direct destruction of ACE2 by SARS-CoV-2 binding likely participates in the loss of regulation of bradykinin levels, given ACE2's normal role in degrading vasodilatory des-Arg9-bradykinin [11].
Mechanism Of Action and Pharmacodynamic Effects Click here for help
Icatibant is an antagonist of the bradykinin B2 receptor (BDKRB2). Activation of this receptor produces inflammatory symptoms such as swelling, redness, increased temperature and pain, by mediating increased blood vessel permeability and dilation and causing contraction of smooth muscle cells. Therefore antagonism of receptor activation negates these effects.
Clinical Trials
Clinical Trial ID Title Type Source Comment References
NCT04488081 I-SPY COVID-19 TRIAL: An Adaptive Platform Trial for Critically Ill Patients Phase 2 Interventional QuantumLeap Healthcare Collaborative
External links Click here for help
For extended ADME data see the following:

Electronic Medicines Compendium (eMC)
Drugs.com
European Medicines Agency (EMA)