DT-Web

DB06196 - Icatibant


Identification
Name Icatibant
Accession Number DB06196
Type small molecule
Description Icatibant (Firazyr) is a synthetic peptidomimetic drug consisting of ten amino acids, and acts as 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 and FDA approved on August 25, 2011.
Structure
MOL SDF PDB SMILES InChI
Categories (*)
Molecular Weight 1304.522
Groups approved
Monoisotopic Weight 1303.660794719
Pharmacology
Indication Approved for use in acute attacks of hereditary angioedema (HAE). Investigated for use/treatment in angioedema, liver disease, and burns and burn infections.
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 in the mediation 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. In patients with HAE, they have an absent or dysfunctional C1-esterase inhibitor. This inhibitor is responsible for the production of bradykinin in which displacement of bradykinin from B2 receptors by icatibant has an inhibitory effect on the receptor for a relatively long time.
Absorption The absolute bioavailability of icatibant following a 30 mg subcutaneous dose is approximately 97%. Maximum plasma concentrations (Cmax) of 974 ? 280 ng/mL was reached when a single subcutaneous dose of 30 mg was administered. The AUC was 2165 ? 568 ng?hr/mL. Icatibant did not accumulate following multiple doses.
Protein binding Not Available
Biotransformation Icatibant is metabolized by proteolytic enzymes into inactive metabolites. The cytochrome P450 enzyme system is not involved with the metabolism of icatibant.
Route of elimination Urine (<10% unchanged)
Toxicity Not Available
Affected organisms
  • Humans and other mammals
Interactions
Drug Interactions
Drug Mechanism of interaction
Benazepril Icatibant may attenuate the antihypertensive effect of ACE inhibitors by pharmacodynamic antagonism. Monitor concomitant therapy closely.
Captopril Icatibant may attenuate the antihypertensive effect of ACE inhibitors by pharmacodynamic antagonism. Monitor concomitant therapy closely.
Enalapril Icatibant may attenuate the antihypertensive effect of ACE inhibitors by pharmacodynamic antagonism. Monitor concomitant therapy closely.
Fosinopril Icatibant may attenuate the antihypertensive effect of ACE inhibitors by pharmacodynamic antagonism. Monitor concomitant therapy closely.
Moexipril Icatibant may attenuate the antihypertensive effect of ACE inhibitors by pharmacodynamic antagonism. Monitor concomitant therapy closely.
Perindopril Icatibant may attenuate the antihypertensive effect of ACE inhibitors by pharmacodynamic antagonism. Monitor concomitant therapy closely.
Quinapril Icatibant may attenuate the antihypertensive effect of ACE inhibitors by pharmacodynamic antagonism. Monitor concomitant therapy closely.
Ramipril Icatibant may attenuate the antihypertensive effect of ACE inhibitors by pharmacodynamic antagonism. Monitor concomitant therapy closely.
Trandolapril Icatibant may attenuate the antihypertensive effect of ACE inhibitors by pharmacodynamic antagonism. Monitor concomitant therapy closely.
Food Interactions Not Available

Targets


B2 bradykinin receptor
Name B2 bradykinin receptor
Gene Name BDKRB2
Pharmacological action yes
Actions antagonist
References
  • Privitera PJ, Beckstead RM, Yates P, Walgren R: Autoradiographic localization of [125I-Tyr0]bradykinin binding sites in brains of Wistar-Kyoto and spontaneously hypertensive rats. Cell Mol Neurobiol. 2003 Oct;23(4-5):805-15. - Pubmed
  • Chen X, Ji ZL, Chen YZ: TTD: Therapeutic Target Database. Nucleic Acids Res. 2002 Jan 1;30(1):412-5. - Pubmed
DTHybrid score 1.3927
Aminopeptidase N
Name Aminopeptidase N
Gene Name ANPEP
Pharmacological action unknown
Actions inhibitor
References
  • Bawolak MT, Fortin JP, Vogel LK, Adam A, Marceau F: The bradykinin B2 receptor antagonist icatibant (Hoe 140) blocks aminopeptidase N at micromolar concentrations: off-target alterations of signaling mediated by the bradykinin B1 and angiotensin receptors. Eur J Pharmacol. 2006 Dec 3;551(1-3):108-11. Epub 2006 Sep 8. - Pubmed
DTHybrid score 1.0811

Predictions


Id Partner name Gene Name Score
6843 Aminopeptidase N pepN 1.0811
890 Niemann-Pick C1-like protein 1 NPC1L1 0.0654
117 Sterol O-acyltransferase 1 SOAT1 0.0514
6176 UDP-glucuronosyltransferase 1-3 UGT1A3 0.0294
6178 UDP-glucuronosyltransferase 2B7 UGT2B7 0.0275
1709 Canalicular multispecific organic anion transporter 2 ABCC3 0.0274
6022 UDP-glucuronosyltransferase 1-1 UGT1A1 0.0268
1490 Solute carrier organic anion transporter family member 1B1 SLCO1B1 0.0242
1732 ATP-binding cassette sub-family G member 2 ABCG2 0.0225
1735 Canalicular multispecific organic anion transporter 1 ABCC2 0.0224
1588 Multidrug resistance protein 1 ABCB1 0.0174
4512 Cytochrome P450 3A4 CYP3A4 0.0153
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