U.S. Department of Health & Human Services Divider Arrow National Institutes of Health Divider Arrow NCATS

Details

Stereochemistry ABSOLUTE
Molecular Formula C59H89N19O13S
Molecular Weight 1304.5259
Optical Activity UNSPECIFIED
Defined Stereocenters 12 / 12
E/Z Centers 0
Charge 0

SHOW SMILES / InChI
Structure of ICATIBANT

SMILES

c1ccc2CN([C@]([H])(Cc2c1)C(=O)N3[C@@]4([H])CCCC[C@@]4([H])C[C@@]3([H])C(=N[C@@]([H])(CCCNC(=N)N)C(=O)O)O)C(=O)[C@]([H])(CO)N=C([C@]([H])(Cc5cccs5)N=C(CN=C([C@]6([H])C[C@]([H])(CN6C(=O)[C@]7([H])CCCN7C(=O)[C@]([H])(CCCNC(=N)N)N=C([C@@]([H])(CCCNC(=N)N)N)O)O)O)O)O

InChI

InChIKey=QURWXBZNHXJZBE-SKXRKSCCSA-N
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

HIDE SMILES / InChI

Description
Curator's Comment:: http://www.drugbank.ca/drugs/DB06196

Icatibant (trade name 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. Icatibant inhibits bradykinin from binding the B2 receptor and thereby treats the clinical symptoms of an acute, episodic attack of HAE.

CNS Activity

Curator's Comment:: Icatibant has low protein binding at around 44% and the volume of distribution is 20 to 25 L, consistent with distribution to include sites of swelling. Animal studies indicate that icatibant is poorly distributed into adipose tissue and does not appear to cross the blood brain barrier

Approval Year

Targets

Targets

Primary TargetPharmacologyConditionPotency
1.07 nM [IC50]
Conditions

Conditions

ConditionModalityTargetsHighest PhaseProduct
Primary
FIRAZYR

Approved Use

Indicated for the treatment of acute attacks of hereditary angioedema (HAE) in adults 18 years of age and older.

Launch Date

1.31423037E12
Cmax

Cmax

ValueDoseCo-administeredAnalytePopulation
974 ng/mL
30 mg single, subcutaneous
dose: 30 mg
route of administration: Subcutaneous
experiment type: SINGLE
co-administered:
ICATIBANT plasma
Homo sapiens
population: HEALTHY
age: ADULT
sex: UNKNOWN
food status: UNKNOWN
1190 ng/mL
30 mg single, subcutaneous
dose: 30 mg
route of administration: subcutaneous
experiment type: single
co-administered:
ICATIBANT plasma
Homo sapiens
population: healthy
age: Adults
sex:
food status:
405 ng/mL
30 mg single, subcutaneous
dose: 30 mg
route of administration: subcutaneous
experiment type: single
co-administered:
ICATIBANT plasma
Homo sapiens
population: unhealthy
age:
sex:
food status:
AUC

AUC

ValueDoseCo-administeredAnalytePopulation
2165 ng × h/mL
30 mg single, subcutaneous
dose: 30 mg
route of administration: Subcutaneous
experiment type: SINGLE
co-administered:
ICATIBANT plasma
Homo sapiens
population: HEALTHY
age: ADULT
sex: UNKNOWN
food status: UNKNOWN
2320 ng*h/mL
30 mg single, subcutaneous
dose: 30 mg
route of administration: subcutaneous
experiment type: single
co-administered:
ICATIBANT plasma
Homo sapiens
population: healthy
age: Adults
sex:
food status:
2320 ng*h/mL
30 mg single, subcutaneous
dose: 30 mg
route of administration: subcutaneous
experiment type: single
co-administered:
ICATIBANT plasma
Homo sapiens
population: healthy
age: Adults
sex:
food status:
1198 ng*h/mL
30 mg single, subcutaneous
dose: 30 mg
route of administration: subcutaneous
experiment type: single
co-administered:
ICATIBANT plasma
Homo sapiens
population: unhealthy
age:
sex:
food status:
1506 ng*h/mL
30 mg single, subcutaneous
dose: 30 mg
route of administration: subcutaneous
experiment type: single
co-administered:
ICATIBANT plasma
Homo sapiens
population: unhealthy
age:
sex:
food status:
611 ng*h/mL
30 mg single, subcutaneous
dose: 30 mg
route of administration: subcutaneous
experiment type: single
co-administered:
ICATIBANT plasma
Homo sapiens
population: unhealthy
age:
sex:
food status:
T1/2

T1/2

ValueDoseCo-administeredAnalytePopulation
1.4 h
30 mg single, subcutaneous
dose: 30 mg
route of administration: Subcutaneous
experiment type: SINGLE
co-administered:
ICATIBANT plasma
Homo sapiens
population: HEALTHY
age: ADULT
sex: UNKNOWN
food status: UNKNOWN
1.77 h
30 mg single, subcutaneous
dose: 30 mg
route of administration: subcutaneous
experiment type: single
co-administered:
ICATIBANT plasma
Homo sapiens
population: healthy
age: Adults
sex:
food status:
Funbound

Funbound

ValueDoseCo-administeredAnalytePopulation
56%
30 mg 1 times / day unknown, subcutaneous
dose: 30 mg
route of administration: Subcutaneous
experiment type: UNKNOWN
co-administered:
ICATIBANT plasma
Homo sapiens
population: UNKNOWN
age: ADULT
sex: UNKNOWN
food status: UNKNOWN
Doses

Doses

DosePopulationAdverse events​
90 mg single, subcutaneous
Highest studied dose
Dose: 90 mg
Route: subcutaneous
Route: single
Dose: 90 mg
Sources: Page: p.109
healthy, 18–50
n = 72
Health Status: healthy
Age Group: 18–50
Sex: M+F
Population Size: 72
Sources: Page: p.109
0.15 mg/kg multiple, intravenous
Highest studied dose
Dose: 0.15 mg/kg
Route: intravenous
Route: multiple
Dose: 0.15 mg/kg
Sources: Page: p.61
healthy
n = 6
Health Status: healthy
Sex: M
Population Size: 6
Sources: Page: p.61
3.2 mg/kg single, intravenous
Highest studied dose
Dose: 3.2 mg/kg
Route: intravenous
Route: single
Dose: 3.2 mg/kg
Sources: Page: p.61
healthy
n = 4
Health Status: healthy
Sex: M
Population Size: 4
Sources: Page: p.61
30 mg 2 times / day multiple, subcutaneous
Recommended
Dose: 30 mg, 2 times / day
Route: subcutaneous
Route: multiple
Dose: 30 mg, 2 times / day
Sources: Page: p.1
unhealthy
Health Status: unhealthy
Condition: Acute attacks of hereditary angioedema
Sources: Page: p.1
Disc. AE: Laryngeal disorder...
AEs leading to
discontinuation/dose reduction:
Laryngeal disorder
Sources: Page: p.1
AEs

AEs

AESignificanceDosePopulation
Laryngeal disorder Disc. AE
30 mg 2 times / day multiple, subcutaneous
Recommended
Dose: 30 mg, 2 times / day
Route: subcutaneous
Route: multiple
Dose: 30 mg, 2 times / day
Sources: Page: p.1
unhealthy
Health Status: unhealthy
Condition: Acute attacks of hereditary angioedema
Sources: Page: p.1
Overview

OverviewOther

Other InhibitorOther SubstrateOther Inducer








Drug as perpetrator​

Drug as perpetrator​

TargetModalityActivityMetaboliteClinical evidence
no
no
no
no
no
no
no
no
no
no
no
Drug as victimTox targets

Tox targets

TargetModalityActivityMetaboliteClinical evidence
PubMed

PubMed

TitleDatePubMed
Inhibition of bradykinin-induced vasodilation in human forearm vasculature by icatibant, a potent B2-receptor antagonist.
1994 Oct
Patents

Patents

Sample Use Guides

30 mg administered by subcutaneous (SC) injection in the abdominal area. Additional doses may be administered at intervals of at least 6 hours if response is inadequate or if symptoms recur. No more than 3 doses may be administered in any 24 hour period.
Route of Administration: Other
In Vitro Use Guide
In vitro studies indicated Hoe 140 as a highly potent bradykinin antagonist. In isolated organ preparations Hoe 140 inhibited bradykinin-induced contractions concentration dependently, with IC50-values in the guinea-pig ileum preparation of 11 mM. In the rat uterus preparation the IC50 value for Hoe 140 was 4.9 nM. In the guinea-pig isolated pulmonary artery IC50 was 5.4 nM. In cultured bovine endothelial cells, Hoe 140 antagonized (IC50 = 100 nM) bradykinin-induced endothelium-derived relaxing factor (EDRF) release and the bradykinin-induced increase in cytosolic free calcium (IC50 = 1 nM).
Name Type Language
ICATIBANT
EMA EPAR   INN   MI   VANDF   WHO-DD  
INN  
Official Name English
L-ARGININE, D-ARGINYL-L-ARGINYL-L-PROLYL-TRANS-4-HYDROXY-L-PROLYLGLYCYL-3-(2-THIENYL)-L-ALANYL-L-SERYL-D-1,2,3,4-TETRAHYDRO-3-ISOQUINOLINECARBONYL-L-(2.ALPHA.,3A.BETA.,7A.BETA.)-OCTAHYDRO-1H-INDOLE-2-CARBONYL-
Common Name English
ICATIBANT [VANDF]
Common Name English
ICATIBANT [MI]
Common Name English
(R)-ARGINYL-(S)-ARGINYL-(S)-PROLYL-(2S,4R)-(4-HYDROXYPROLYL)GLYCYL-(S)-(3-(2-THIENYL)ALANYL)-(S)-SERYL-(R)-((1,2,3,4-TETRAHYDRO-3-ISOQUINOLYL)CARBONYL)-(2S,3AS,7AS)-((HEXAHYDRO-2-INDOLINYL)CARBONYL)-(S)-ARGININE
Common Name English
ICATIBANT [EMA EPAR]
Common Name English
ICATIBANT [INN]
Common Name English
ICATIBANT [WHO-DD]
Common Name English
Classification Tree Code System Code
FDA ORPHAN DRUG 176203
Created by admin on Sat Jun 26 04:37:46 UTC 2021 , Edited by admin on Sat Jun 26 04:37:46 UTC 2021
NDF-RT N0000182965
Created by admin on Sat Jun 26 04:37:46 UTC 2021 , Edited by admin on Sat Jun 26 04:37:46 UTC 2021
NCI_THESAURUS C257
Created by admin on Sat Jun 26 04:37:46 UTC 2021 , Edited by admin on Sat Jun 26 04:37:46 UTC 2021
WHO-ATC C01EB19
Created by admin on Sat Jun 26 04:37:46 UTC 2021 , Edited by admin on Sat Jun 26 04:37:46 UTC 2021
FDA ORPHAN DRUG 184804
Created by admin on Sat Jun 26 04:37:46 UTC 2021 , Edited by admin on Sat Jun 26 04:37:46 UTC 2021
WHO-VATC QB06AC02
Created by admin on Sat Jun 26 04:37:46 UTC 2021 , Edited by admin on Sat Jun 26 04:37:46 UTC 2021
EMA ASSESSMENT REPORTS FIRAZYR (AUTHORIZED: ANGIOEDEMAS, HEREDITARY)
Created by admin on Sat Jun 26 04:37:46 UTC 2021 , Edited by admin on Sat Jun 26 04:37:46 UTC 2021
WHO-ATC B06AC02
Created by admin on Sat Jun 26 04:37:46 UTC 2021 , Edited by admin on Sat Jun 26 04:37:46 UTC 2021
Code System Code Type Description
NDF-RT
N0000182964
Created by admin on Sat Jun 26 04:37:46 UTC 2021 , Edited by admin on Sat Jun 26 04:37:46 UTC 2021
PRIMARY Bradykinin B2 Receptor Antagonists [MoA]
NCI_THESAURUS
C98883
Created by admin on Sat Jun 26 04:37:46 UTC 2021 , Edited by admin on Sat Jun 26 04:37:46 UTC 2021
PRIMARY
CAS
130308-48-4
Created by admin on Sat Jun 26 04:37:46 UTC 2021 , Edited by admin on Sat Jun 26 04:37:46 UTC 2021
PRIMARY
DRUG BANK
DB06196
Created by admin on Sat Jun 26 04:37:46 UTC 2021 , Edited by admin on Sat Jun 26 04:37:46 UTC 2021
PRIMARY
DRUG CENTRAL
4186
Created by admin on Sat Jun 26 04:37:46 UTC 2021 , Edited by admin on Sat Jun 26 04:37:46 UTC 2021
PRIMARY
WIKIPEDIA
ICATIBANT
Created by admin on Sat Jun 26 04:37:46 UTC 2021 , Edited by admin on Sat Jun 26 04:37:46 UTC 2021
PRIMARY
RXCUI
1148138
Created by admin on Sat Jun 26 04:37:46 UTC 2021 , Edited by admin on Sat Jun 26 04:37:46 UTC 2021
PRIMARY RxNorm
MESH
C065679
Created by admin on Sat Jun 26 04:37:46 UTC 2021 , Edited by admin on Sat Jun 26 04:37:46 UTC 2021
PRIMARY
MERCK INDEX
M6192
Created by admin on Sat Jun 26 04:37:46 UTC 2021 , Edited by admin on Sat Jun 26 04:37:46 UTC 2021
PRIMARY Merck Index
PUBCHEM
6918173
Created by admin on Sat Jun 26 04:37:46 UTC 2021 , Edited by admin on Sat Jun 26 04:37:46 UTC 2021
PRIMARY
FDA UNII
7PG89G35Q7
Created by admin on Sat Jun 26 04:37:46 UTC 2021 , Edited by admin on Sat Jun 26 04:37:46 UTC 2021
PRIMARY
ChEMBL
CHEMBL2028850
Created by admin on Sat Jun 26 04:37:46 UTC 2021 , Edited by admin on Sat Jun 26 04:37:46 UTC 2021
PRIMARY
INN
6922
Created by admin on Sat Jun 26 04:37:46 UTC 2021 , Edited by admin on Sat Jun 26 04:37:46 UTC 2021
PRIMARY
EVMPD
SUB08104MIG
Created by admin on Sat Jun 26 04:37:46 UTC 2021 , Edited by admin on Sat Jun 26 04:37:46 UTC 2021
PRIMARY
IUPHAR
667
Created by admin on Sat Jun 26 04:37:46 UTC 2021 , Edited by admin on Sat Jun 26 04:37:46 UTC 2021
PRIMARY