Icatibant

Các tên gọi khác (1) :

HOE 140

anti inflammatory agents non steroidal, adrenergic beta antagonists

Thuốc Gốc

Small Molecule

CAS: 130308-48-4

ATC: B06AC02

CTHH: C₅₉H₈₉N₁₉O₁₃S

PTK: 1304.522

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.

Nhận Dạng Quốc Tế & Đặc Tính Hóa Học

Công thức hóa học

C₅₉H₈₉N₁₉O₁₃S

Phân tử khối

1304.522

Monoisotopic mass

1303.660794719

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

InChI Key

InChIKey=QURWXBZNHXJZBE-MCDGZUPGSA-N

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}pyrrolidin-2-yl)carbonyl]-4-hydroxypyrrolidin-2-yl]formamido}acetamido)-3-(thiophen-2-yl)propanamido]-3-hydroxypropanoyl]-1,2,3,4-tetrahydroisoquinolin-3-yl}carbonyl)-octahydro-1H-indol-2-yl]formamido}-5-[(diaminomethylidene)amino]pentanoic acid

Traditional IUPAC Name

icatibant

SMILES

[H][C@]12CC(N(C(=O)C3CC4=CC=CC=C4CN3C(=O)[C@H](CO)NC(=O)[C@H](CC3=CC=CS3)NC(=O)CNC(=O)C3C[C@@H](O)CN3C(=O)C3CCCN3C(=O)C(CCCN=C(N)N)NC(=O)[C@H](N)CCCN=C(N)N)[C@@]1([H])CCCC2)C(=O)N[C@@H](CCCN=C(N)N)C(O)=O

Độ hòa tan

1 mg/mL

logP

-8

logS

-4.4

pKa (strongest acidic)

3.46

pKa (Strongest Basic)

11.45

PSA

523.72 Å²

Refractivity

332.91 m³·mol^-1

Polarizability

137.03 Å³

Rotatable Bond Count

H Bond Acceptor Count

H Bond Donor Count

Physiological Charge

Number of Rings

Bioavailability

MDDR-Like Rule

true

Dược Lực Học : Icatibant is a potent, specific, competitive, 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). If an IV dose of 0.4 and 0.8 mg/kg was infused over 4 hours, one may observe an inhibited response to bradykinin challenge for 6 - 8 hours following completion of infusion.

Cơ Chế Tác Dụng : 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. 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.

Dược Động Học :

▧ 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.
▧ Volume of Distribution :
Vdss, subcutaneous injection = 29.0 ± 8.7 L.
▧ Metabolism :
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)
▧ Half Life :
After subcutaneous administration, mean elimination half-life was 1.4 ± 0.4 hours.
▧ Clearance :
Plasma clearance following subcutaneous administration was 245 ± 58 mL/min.

Chỉ Định : Approved for use in acute attacks of hereditary angioedema (HAE). Investigated for use/treatment in angioedema, liver disease, and burns and burn infections.

Tương Tác Thuốc :

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.

Liều Lượng & Cách Dùng : Solution - Subcutaneous - 30 mg/3 mL

Dữ Kiện Thương Mại

Nhà Sản Xuất

Công ty : Shire

Sản phẩm biệt dược : Firazyr

Tài Liệu Tham Khảo Thêm

drugbank

http://www.drugbank.ca/drugs/DB06196

PubChem Compound

http://pubchem.ncbi.nlm.nih.gov/summary/summary.cgi?sid=71364

PubChem Substance

http://pubchem.ncbi.nlm.nih.gov/summary/summary.cgi?sid=99443237

KEGG Drug

http://www.genome.jp/dbget-bin/www_bget?drug:D04492

ChemSpider

http://www.chemspider.com/Chemical-Structure.64461.html

BindingDB

http://www.bindingdb.org/bind/chemsearch/marvin/MolStructure.jsp?monomerid=50142947

National Drug Code Directory

http://www.hipaaspace.com/Medical_Billing/Coding/National.Drug.Codes/PDF/54092-702-02

PharmGKB

http://www.pharmgkb.org/drug/PA164749185

Wikipedia

http://en.wikipedia.org/wiki/Icatibant

RxList

http://www.rxlist.com/firazyr-drug.htm

Drugs.com

http://www.drugs.com/cdi/icatibant.html

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