Icatibant

Icatibant

Clinical data
Trade names	Firazyr
AHFS/Drugs.com	International Drug Names
License data	EU EMA: Firazyr US FDA: Icatibant
Pregnancy category	US: C (Risk not ruled out)
Routes of administration	subcutaneous
ATC code	B06AC02 (WHO)
Legal status
Legal status	US: ℞-only
Identifiers
IUPAC name (2S)-2-[[(3aS,7aS)-1-[2-[(2S)-2-[[(2S)- 2-[[2-[[(4R)-1-[1-[2-[[(2R)-2-amino-5-(diaminomethylideneamino) pentanoyl]amino]-5-(diaminomethylideneamino)pentanoyl]pyrrolidine- 2-carbonyl]-4-hydroxypyrrolidine-2-carbonyl]amino]acetyl]amino]- 3-thiophen-2-ylpropanoyl]amino]-3-hydroxypropanoyl] 3,4-dihydro-1H-isoquinoline-3-carbonyl] 2,3,3a,4,5,6,7,7a-octahydroindole-2-carbonyl]amino]- 5-(diaminomethylideneamino)pentanoic acid
CAS Number	130308-48-4
PubChem (CID)	71364
IUPHAR/BPS	667
DrugBank	DB06196
ChemSpider	16736634
UNII	7PG89G35Q7
ChEBI	CHEBI:68556
ChEMBL	CHEMBL1743581
Chemical and physical data
Formula	C59H89N19O13S
Molar mass	1304.52 g/mol
3D model (Jmol)	Interactive image
SMILES C1CC[C@H]2[C@@H](C1)CC(N2C(=O)C3CC4=CC=CC=C4CN3C(=O)[C@H](CO)NC(=O)[C@H](CC5=CC=CS5)NC(=O)CNC(=O)C6C[C@H](CN6C(=O)C7CCCN7C(=O)C(CCCN=C(N)N)NC(=O)[C@@H](CCCN=C(N)N)N)O)C(=O)N[C@@H](CCCN=C(N)N)C(=O)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 Key:QURWXBZNHXJZBE-OVZQYVDUSA-N
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Icatibant (trade name Firazyr, alternative name Hoe 140, JE 049^[1]) is a peptidomimetic drug consisting of ten amino acids, which is a selective and specific antagonist of bradykinin B2 receptors. It has been approved by the European Commission for the symptomatic treatment of acute attacks^[2][3] of hereditary angioedema (HAE) in adults with C1-esterase-inhibitor deficiency.

Mechanism of action

Bradykinin is a peptide-based hormone that is formed locally in tissues, very often in response to a trauma. It increases vessel permeability, dilates blood vessels and causes smooth muscle cells to contract. Bradykinin plays an important role as the mediator of pain. Surplus bradykinin is responsible for the typical symptoms of inflammation, such as swelling, redness, overheating and pain. These symptoms are mediated by activation of bradykinin B2 receptors. Icatibant acts as a bradykinin inhibitor by blocking the binding of native bradykinin to the bradykinin B2 receptor.

Regulatory status

Icatibant has received orphan drug status in Australia, EU, Switzerland and US for the treatment of angiotensin-converting-enzyme inhibitor (ACE-1) induced angioedema (HAE).

In the EU, the approval by the European Commission (July 2008) allows Jerini to market Firazyr in the European Union's 27 member states, as well as Switzerland, Lichtenstein and Iceland, making it the first product to be approved in all EU countries for the treatment of HAE.^[2] In the US, the drug was granted FDA approval on August 25, 2011.^[4]

See also

• Ecallantide, another drug for the treatment of HAE

References

1. "Icatibant: HOE 140, JE 049, JE049.".
2. "Jerini Receives European Commission Approval for Firazyr (Icatibant) in the Treatment of HAE" (Press release). Jerini AG. 2008-07-15. Retrieved 2008-07-22.
3. "Jerini Receives Positive CHMP Opinion Recommending European Approval for Icatibant in the Treatment of HAE; FDA Issues Not Approvable Letter" (Press release). Jerini AG. 2008-04-24. Retrieved 2008-07-22.
4. "FDA Approves Shire's FIRAZYR (icatibant injection) for Acute Attacks of Hereditary Angioedema (HAE)" (Press release). Shire. Retrieved 2011-08-28.