ICATIBANT

Details

Stereochemistry	ABSOLUTE
Molecular Formula	C59H89N19O13S
Molecular Weight	1304.522
Optical Activity	UNSPECIFIED
Defined Stereocenters	12 / 12
E/Z Centers	0
Charge	0

SHOW SMILES / InChI

Structure Search

SMILES

[H][C@]12C[C@]([H])(N(C(=O)[C@@]3([H])CC4=C(CN3C(=O)[C@H](CO)NC(=O)[C@H](CC5=CC=CS5)NC(=O)CNC(=O)[C@]6([H])C[C@@H](O)CN6C(=O)[C@@H]7CCCN7C(=O)[C@H](CCCNC(N)=N)NC(=O)[C@H](N)CCCNC(N)=N)C=CC=C4)[C@@]1([H])CCCC2)C(=O)N[C@@H](CCCNC(N)=N)C(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
Sources: http://www.accessdata.fda.gov/drugsatfda_docs/label/2011/022150s000lbl.pdf
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

Originator

Approval Year

Targets

Primary Target	Pharmacology	Condition	Potency
Bradykinin B2 receptor 3 Target ID: CHEMBL2501 Sources: http://www.accessdata.fda.gov/drugsatfda_docs/label/2011/022150s000lbl.pdf	Antagonist 2778		1.07 nM [IC50]

Conditions

Condition	Modality	Targets	Highest Phase	Product
Hereditary angioedema 3 Sources: http://www.accessdata.fda.gov/drugsatfda_docs/label/2011/022150s000lbl.pdf	Primary		Approved 8429	FIRAZYR Approved Use Indicated for the treatment of acute attacks of hereditary angioedema (HAE) in adults 18 years of age and older. Launch Date 2011

C_max

Value	Dose	Analyte	Population
974 ng/mL DRUG LABEL https://www.accessdata.fda.gov/drugsatfda_docs/label/2020/022150s012s013lbl.pdf	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 Clinical Trial https://clinicaltrials.gov/ct2/show/NCT02045264	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 Clinical Trial https://clinicaltrials.gov/ct2/show/NCT03888755	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

Value	Dose	Analyte	Population
2165 ng × h/mL DRUG LABEL https://www.accessdata.fda.gov/drugsatfda_docs/label/2020/022150s012s013lbl.pdf	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 Clinical Trial https://clinicaltrials.gov/ct2/show/NCT02045264	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 Clinical Trial https://clinicaltrials.gov/ct2/show/NCT02045264	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 Clinical Trial https://clinicaltrials.gov/ct2/show/NCT03888755	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 Clinical Trial https://clinicaltrials.gov/ct2/show/NCT03888755	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 Clinical Trial https://clinicaltrials.gov/ct2/show/NCT03888755	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:

T_1/2

Value	Dose	Co-administered	Analyte	Population
1.4 h DRUG LABEL https://www.accessdata.fda.gov/drugsatfda_docs/label/2020/022150s012s013lbl.pdf	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 Clinical Trial https://clinicaltrials.gov/ct2/show/NCT02045264	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:

F_unbound

Value	Dose	Co-administered	Analyte	Population
56% REVIEW https://pubmed.ncbi.nlm.nih.gov/20030426/	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

Dose	Population	Adverse events
90 mg single, subcutaneous Highest studied dose Dose: 90 mg Route: subcutaneous Route: single Dose: 90 mg Sources: https://pubmed.ncbi.nlm.nih.gov/27128215 Page: p.109	healthy, 18–50 n = 72 Health Status: healthy Age Group: 18–50 Sex: M+F Population Size: 72 Sources: https://pubmed.ncbi.nlm.nih.gov/27128215 Page: p.109	Sources: https://pubmed.ncbi.nlm.nih.gov/27128215 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: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2011/022150Orig1s000ClinPharmR.pdf Page: p.61	healthy n = 6 Health Status: healthy Sex: M Population Size: 6 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2011/022150Orig1s000ClinPharmR.pdf Page: p.61	Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2011/022150Orig1s000ClinPharmR.pdf 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: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2011/022150Orig1s000ClinPharmR.pdf Page: p.61	healthy n = 4 Health Status: healthy Sex: M Population Size: 4 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2011/022150Orig1s000ClinPharmR.pdf Page: p.61	Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2011/022150Orig1s000ClinPharmR.pdf 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: https://www.accessdata.fda.gov/drugsatfda_docs/label/2011/022150s000lbl.pdf Page: p.1	unhealthy Health Status: unhealthy Condition: Acute attacks of hereditary angioedema Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2011/022150s000lbl.pdf Page: p.1	Disc. AE: Laryngeal disorder... AEs leading to discontinuation/dose reduction: Laryngeal disorder Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2011/022150s000lbl.pdf Page: p.1

AEs

AE	Significance	Dose	Population
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: https://www.accessdata.fda.gov/drugsatfda_docs/label/2011/022150s000lbl.pdf Page: p.1	unhealthy Health Status: unhealthy Condition: Acute attacks of hereditary angioedema Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2011/022150s000lbl.pdf Page: p.1

Overview

CYP3A4	CYP2C9	CYP2D6	hERG
inhibitor 1587 inducer 781	inhibitor 1767	inhibitor 1852	inhibitor 1612

OverviewOther

Other Inhibitor	Other Substrate	Other Inducer
CYP1A2 1524 CYP2A6 707 CYP2B6 810 CYP2C8 911 CYP2C19 1478 CYP2E1 882	CYP 270	CYP1A2 701

Drug as perpetrator

Target	Modality	Activity
CYP1A2 1692	inducer 1573 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2011/022150Orig1s000PharmR.pdf#page=174, https://www.accessdata.fda.gov/drugsatfda_docs/nda/2011/022150Orig1s000ClinPharmR.pdf#page=49 Page: 130, 166, 174, 176, (ClinPharm) 49	no
CYP1A2 1692	inhibitor 3277 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2011/022150Orig1s000PharmR.pdf#page=173, https://www.accessdata.fda.gov/drugsatfda_docs/nda/2011/022150Orig1s000ClinPharmR.pdf#page=49 Page: 173-174, (ClinPharm) 49	no
CYP2A6 739	inhibitor 3277 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2011/022150Orig1s000PharmR.pdf#page=173, https://www.accessdata.fda.gov/drugsatfda_docs/nda/2011/022150Orig1s000ClinPharmR.pdf#page=49 Page: 173-174, (ClinPharm) 49	no
CYP2B6 1001	inhibitor 3277 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2011/022150Orig1s000PharmR.pdf#page=173, https://www.accessdata.fda.gov/drugsatfda_docs/nda/2011/022150Orig1s000ClinPharmR.pdf#page=49 Page: 173-174, (ClinPharm) 49	no
CYP2C19 1553	inhibitor 3277 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2011/022150Orig1s000PharmR.pdf#page=173, https://www.accessdata.fda.gov/drugsatfda_docs/nda/2011/022150Orig1s000ClinPharmR.pdf#page=49 Page: 173-174, (ClinPharm) 49	no
CYP2C8 965	inhibitor 3277 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2011/022150Orig1s000PharmR.pdf#page=173, https://www.accessdata.fda.gov/drugsatfda_docs/nda/2011/022150Orig1s000ClinPharmR.pdf#page=49 Page: 173-174, (ClinPharm) 49	no
CYP2C9 1819	inhibitor 3277 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2011/022150Orig1s000PharmR.pdf#page=173, https://www.accessdata.fda.gov/drugsatfda_docs/nda/2011/022150Orig1s000ClinPharmR.pdf#page=49 Page: 173-174, (ClinPharm) 49	no
CYP2D6 1891	inhibitor 3277 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2011/022150Orig1s000PharmR.pdf#page=173, https://www.accessdata.fda.gov/drugsatfda_docs/nda/2011/022150Orig1s000ClinPharmR.pdf#page=49 Page: 173-174, (ClinPharm) 49	no
CYP2E1 970	inhibitor 3277 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2011/022150Orig1s000PharmR.pdf#page=173, https://www.accessdata.fda.gov/drugsatfda_docs/nda/2011/022150Orig1s000ClinPharmR.pdf#page=49 Page: 173-174, (ClinPharm) 49	no
CYP3A4 1925	inducer 1573 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2011/022150Orig1s000PharmR.pdf#page=174, https://www.accessdata.fda.gov/drugsatfda_docs/nda/2011/022150Orig1s000ClinPharmR.pdf#page=49 Page: 130, 166, 174, 176, (ClinPharm) 49	no
CYP3A4 1925	inhibitor 3277 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2011/022150Orig1s000PharmR.pdf#page=173, https://www.accessdata.fda.gov/drugsatfda_docs/nda/2011/022150Orig1s000ClinPharmR.pdf#page=49 Page: 173-174, (ClinPharm) 49	no

Drug as victim

Target	Modality	Activity	Metabolite
CYP 270	substrate 3367 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2011/022150Orig1s000PharmR.pdf#page=174 Page: 174, 176, 261	no
CYP 270	substrate 3367 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2011/022150Orig1s000PharmR.pdf#page=174 Page: 174, 176, 261	no	M1 13
CYP 270	substrate 3367 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2011/022150Orig1s000PharmR.pdf#page=174 Page: 174, 176, 261	no	M2 9

Tox targets

Target	Modality	Activity	Metabolite	Clinical evidence
hERG 1647	inhibitor 1626 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2011/022150Orig1s000PharmR.pdf#page=129 Page: 129, 164, 260, 475, 575

Sourcing

Vendor/Aggregator	ID	URL
ChEBI	CHEBI:68556	https://www.ebi.ac.uk/chebi/searchId.do?chebiId=CHEBI:68556
ChemicalBook	CB1318492	https://www.chemicalbook.com/ChemicalProductProperty_EN_CB1318492
MolPort	MolPort-039-139-674	https://www.molport.com/shop/molecule-link/MolPort-039-139-674
eMolecules	31216553	https://www.emolecules.com/cgi-bin/more?vid=31216553

PubMed

Title	Date	PubMed
Inhibition of bradykinin-induced vasodilation in human forearm vasculature by icatibant, a potent B2-receptor antagonist.	1994 Oct	7833220

Patents

Sample Use Guides

In Vivo Use Guide

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

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 [WHO-DD]

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

Classification Tree Code System Code

FDA ORPHAN DRUG

176203