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))
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.
The HELM annotation is PEPTIDE1{[dR].(R,[dR]).(P,[dP]).[*C(=O)C1C[C@H](CN1*)O |$_R2;;;;;;;;_R1;$|].G.[Thi].S.[*C(=O)C1Cc2ccccc2CN1* |$_R2;;;;;;;;;;;;;_R1$|].[*C(=O)C1C[C@@H]2CCCC[C@@H]2N1* |$_R2;;;;;;;;;;;;_R1$|].R}$$$$V2.0 (from PubChem).
Click here for help
2D Structure
Click here for help
Click here for structure editor
Click here for help
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
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