(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

• ChemBase ID: 4420
• Molecular Formular: C59H89N19O13S
• Molecular Mass: 1304.52246
• Monoisotopic Mass: 1303.660795
• SMILES: s1c(C[C@H](NC(=O)CNC(=O)C2N(C[C@H](O)C2)C(=O)C2N(CCC2)C(=O)C(NC(=O)[C@H](N)CCCN=C(N)N)CCCN=C(N)N)C(=O)N[C@H](C(=O)N2C(C(=O)N3[C@@H]4[C@H](CC3C(=O)N[C@@H](CCCN=C(N)N)C(=O)O)CCCC4)Cc3c(C2)cccc3)CO)ccc1
• 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
• 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
• InChIKey: QURWXBZNHXJZBE-MCDGZUPGSA-N

NAMES AND DATABASE IDS

Names

• 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
• IUPAC Traditional name: icatibant; (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]-3,4-dihydro-1H-isoquinoline-3-carbonyl}-octahydroindol-2-yl]formamido}-5-[(diaminomethylidene)amino]pentanoic acid
• Brand Name: Firazyr
• Synonyms: JE049; icatibant; Icatibant

Database IDs

• CAS Number: 130308-48-4
• PubChem SID: 160967852; 99443237
• PubChem CID: 71364
• CHEBI ID: 68556
• ATC CODE: B06AC02
• CHEMBL: 1743581
• Chemspider ID: 16736634
• DrugBank ID: DB06196
• IUPHAR ligand ID: 667
• Unique Ingredient Identifier: 7PG89G35Q7
• Wikipedia Title: Icatibant

CALCULATED PROPERTIES

JChem

• Acid pKa: 3.4622498
• H Acceptors: 23
• H Donor: 15
• LogD (pH = 5.5): -14.416425
• LogD (pH = 7.4): -12.670704
• Log P: -7.9869075
• Molar Refractivity: 332.9107 cm^3
• Polarizability: 128.73781 Å^3
• Polar Surface Area: 523.72 Å^2
• Rotatable Bonds: 30
• Lipinski's Rule of Five: false

ALOGPS 2.1

• Log P: -2.32
• LOG S: -4.36
• Solubility (Water): 5.70e-02 g/l

PROPERTIES

Pharmacology Properties

• Admin Routes: subcutaneous
• Legal Status: Rx-only (US)
• Pregnancy Category: C (US)
• US Licence: Icatibant
• EU Licence: Firazyr

DETAILS

DrugBank - DB06196

• Drug Groups: approved; investigational
• 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.
• Indication: Approved for use in hereditary angioedema. Investigated for use/treatment in angioedema, liver disease, and burns and burn infections.
• Pharmacology: Icatibant is a potent, specific and selective peptidomimetic bradykinin beta2-receptor antagonist (pA2 = 9.04). It has a modified peptide structure, and is the first bradykinin receptor antagonist to act on the guinea-pig trachea without demonstrating agonist effects. It also inhibits aminopeptidase N (Ki = 9.1 μM).
• Affected Organisms: Humans and other mammals
• Half Life: Elimination half-lives calculated from linear regression of the mean data were 25, 27 and 29 min after 20, 50 and 100 micrograms kg-1 doses respectively.
• References: 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] ; 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]
• External Links: Wikipedia

REFERENCES

• 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
• 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