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.
Click here for help
2D Structure
Click here for help
Click here for structure editor
SMILES / InChI / InChIKey
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
InChI Key QURWXBZNHXJZBE-MCDGZUPGSA-N
References
1. Amblard M, Daffix I, Bedos P, Bergé G, Pruneau D, Paquet JL, Luccarini JM, Bélichard P, Dodey P, Martinez J. (1999)
Design and synthesis of potent bradykinin agonists containing a benzothiazepine moiety.
J Med Chem, 42 (20): 4185-92. [PMID:10514288]
2. Anderson M. 
We are finally unravelling the mystery of what causes severe covid-19.
Accessed on 22/09/2020. Modified on 22/09/2020. New Scientist, https://institutions.newscientist.com/article/2253987-we-are-finally-unravelling-the-mystery-of-what-causes-severe-covid-19/
3. Aramori I, Zenkoh J, Morikawa N, O'Donnell N, Asano M, Nakamura K, Iwami M, Kojo H, Notsu Y. (1997)
Novel subtype-selective nonpeptide bradykinin receptor antagonists FR167344 and FR173657.
Mol Pharmacol, 51 (2): 171-6. [PMID:9203620]
4. Bastian S, Loillier B, Paquet JL, Pruneau D. (1997)
Stable expression of human kinin B1 receptor in 293 cells: pharmacological and functional characterization.
Br J Pharmacol, 122 (2): 393-9. [PMID:9313952]
5. Burgess GM, Perkins MN, Rang HP, Campbell EA, Brown MC, McIntyre P, Urban L, Dziadulewicz EK, Ritchie TJ, Hallett A et al.. (2000)
Bradyzide, a potent non-peptide B(2) bradykinin receptor antagonist with long-lasting oral activity in animal models of inflammatory hyperalgesia.
Br J Pharmacol, 129 (1): 77-86. [PMID:10694205]
6. De Falco L, Fioravanti A, Galeazzi M, Tenti S. (2013)
Bradykinin and its role in osteoarthritis.
Reumatismo, 65 (3): 97-104. [PMID:23884024]
7. Garvin MR, Alvarez C, Miller JI, Prates ET, Walker AM, Amos BK, Mast AE, Justice A, Aronow B, Jacobson D. (2020)
A mechanistic model and therapeutic interventions for COVID-19 involving a RAS-mediated bradykinin storm.
Elife, 9. DOI: 10.7554/eLife.59177 [PMID:32633718]
8. Gobeil F, Pheng LH, Badini I, Nguyen-Le XK, Pizard A, Rizzi A, Blouin D, Regoli D. (1996)
Receptors for kinins in the human isolated umbilical vein.
Br J Pharmacol, 118 (2): 289-94. [PMID:8735629]
9. Hess JF, Borkowski JA, MacNeil T, Stonesifer GY, Fraher J, Strader CD, Ransom RW. (1994)
Differential pharmacology of cloned human and mouse B2 bradykinin receptors.
Mol Pharmacol, 45: 1-8. [PMID:8302267]
10. Jones C, Phillips E, Davis C, Arbuckle J, Yaqoob M, Burgess GM, Docherty RJ, Webb M, Bevan SJ, McIntyre P. (1999)
Molecular characterisation of cloned bradykinin B1 receptors from rat and human.
Eur J Pharmacol, 374: 423-433. [PMID:10422787]
11. Robinson EL, Alkass K, Bergmann O, Maguire JJ, Roderick HL, Davenport AP. (2020)
Genes encoding ACE2, TMPRSS2 and related proteins mediating SARS-CoV-2 viral entry are upregulated with age in human cardiomyocytes.
J Mol Cell Cardiol, 147: 88-91. [PMID:32818486]
12. Roche JA, Roche R. (2020)
A hypothesized role for dysregulated bradykinin signaling in COVID-19 respiratory complications.
FASEB J, 34 (6): 7265-7269. [PMID:32359101]
13. van de Veerdonk FL, Kouijzer IJE, de Nooijer AH, van der Hoeven HG, Maas C, Netea MG, Brüggemann RJM. (2020)
Outcomes Associated With Use of a Kinin B2 Receptor Antagonist Among Patients With COVID-19.
JAMA Netw Open, 3 (8): e2017708. [PMID:32789513]