ARGATROBAN ANHYDROUS

Details

Stereochemistry	EPIMERIC
Molecular Formula	C23H36N6O5S
Molecular Weight	508.634
Optical Activity	UNSPECIFIED
Defined Stereocenters	3 / 4
E/Z Centers	0
Charge	0

SHOW SMILES / InChI

Structure Search

SMILES

C[C@@H]1CCN([C@H](C1)C(O)=O)C(=O)[C@H](CCCNC(N)=N)NS(=O)(=O)C2=C3NCC(C)CC3=CC=C2

InChI

InChIKey=KXNPVXPOPUZYGB-IOVMHBDKSA-N

InChI=1S/C23H36N6O5S/c1-14-8-10-29(18(12-14)22(31)32)21(30)17(6-4-9-26-23(24)25)28-35(33,34)19-7-3-5-16-11-15(2)13-27-20(16)19/h3,5,7,14-15,17-18,27-28H,4,6,8-13H2,1-2H3,(H,31,32)(H4,24,25,26)/t14-,15?,17+,18-/m1/s1

HIDE SMILES / InChI

Description
Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2011/022485lbl.pdf | https://www.ncbi.nlm.nih.gov/pubmed/25152637 | https://www.drugbank.ca/drugs/DB00278

Argatroban is a synthetic direct thrombin inhibitor derived from L-arginine. Argatroban is a direct thrombin inhibitor that reversibly binds to the thrombin active site. Argatroban does not require the co-factor antithrombin III for antithrombotic activity. Argatroban exerts its anticoagulant effects by inhibiting thrombin-catalyzed or -induced reactions, including fibrin formation; activation of coagulation factors V, VIII, and XIII; protein C; and platelet aggregation. Argatroban is highly selective for thrombin with an inhibitory constant (Ki) of 0.04 µM. At therapeutic concentrations, Argatroban has little or no effect on related serine proteases (trypsin, factor Xa, plasmin, and kallikrein). Argatroban is capable of inhibiting the action of both free and clot-associated thrombin. Argatroban is indicated as an anticoagulant for prophylaxis or treatment of thrombosis in patients with heparin-induced thrombocytopenia. Argatroban is indicated as an anticoagulant in patients with or at risk for heparin-induced thrombocytopenia undergoing percutaneous coronary intervention (PCI).

CNS Activity

Originator

Approval Year

Targets

Primary Target	Pharmacology	Condition	Potency
Thrombin 20 Target ID: CHEMBL204 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2011/022485lbl.pdf \| https://www.ncbi.nlm.nih.gov/pubmed/25824648	Inhibitor 8297		0.04 µM [Ki]

Conditions

Condition	Modality	Targets	Highest Phase	Product
Thrombosis 22 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2011/022485lbl.pdf	Primary		Approved 8429	ARGATROBAN Approved Use Argatroban is a direct thrombin inhibitor indicated: • For prophylaxis or treatment of thrombosis in adult patients with heparin-induced thrombocytopenia (HIT) (1.1) • As an anticoagulant in adults patients with or at risk for HIT undergoing percutaneous coronary intervention (PCI) (1.2) Launch Date 2000
Heparin-induced thrombocytopenia 2 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2011/022485lbl.pdf	Primary		Approved 8429	ARGATROBAN Approved Use Argatroban is a direct thrombin inhibitor indicated: • For prophylaxis or treatment of thrombosis in adult patients with heparin-induced thrombocytopenia (HIT) (1.1) • As an anticoagulant in adults patients with or at risk for HIT undergoing percutaneous coronary intervention (PCI) (1.2) Launch Date 2000

C_max

Value	Dose	Co-administered	Analyte	Population
538.6 ng/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/10730687	2.5 μg/kg/min other, intravenous dose: 2.5 μg/kg/min route of administration: Intravenous experiment type: OTHER co-administered:		ARGATROBAN plasma	Homo sapiens population: HEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN

AUC

Value	Dose	Co-administered	Analyte	Population
1727.7 ng × h/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/10730687	2.5 μg/kg/min other, intravenous dose: 2.5 μg/kg/min route of administration: Intravenous experiment type: OTHER co-administered:		ARGATROBAN plasma	Homo sapiens population: HEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN

T_1/2

Value	Dose	Co-administered	Analyte	Population
60.6 min EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/10730687	2.5 μg/kg/min other, intravenous dose: 2.5 μg/kg/min route of administration: Intravenous experiment type: OTHER co-administered:		ARGATROBAN plasma	Homo sapiens population: HEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN

F_unbound

Value	Dose	Co-administered	Analyte	Population
46% DRUG LABEL https://www.accessdata.fda.gov/drugsatfda_docs/label/2011/022485lbl.pdf			ARGATROBAN serum	Homo sapiens population: UNKNOWN age: UNKNOWN sex: UNKNOWN food status: UNKNOWN

Doses

Dose	Population	Adverse events
125 mg single, intravenous Overdose Dose: 125 mg Route: intravenous Route: single Dose: 125 mg Sources: https://pubmed.ncbi.nlm.nih.gov/16449547/	unhealthy, 74 years n = 1 Health Status: unhealthy Condition: Crohn’s disease, ileorectal fistula Age Group: 74 years Sex: M Population Size: 1 Sources: https://pubmed.ncbi.nlm.nih.gov/16449547/	Sources: https://pubmed.ncbi.nlm.nih.gov/16449547/
125 mg single, intravenous Highest studied dose Dose: 125 mg Route: intravenous Route: single Dose: 125 mg Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2011/022485lbl.pdf Page: 6.1	unhealthy, adult n = 568 Health Status: unhealthy Condition: thrombosis Age Group: adult Sex: unknown Population Size: 568 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2011/022485lbl.pdf Page: 6.1	Other AEs: Haemorrhage... Other AEs: Haemorrhage (57.3%) Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2011/022485lbl.pdf Page: 6.1

AEs

AE	Significance	Dose	Population
Haemorrhage	57.3%	125 mg single, intravenous Highest studied dose Dose: 125 mg Route: intravenous Route: single Dose: 125 mg Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2011/022485lbl.pdf Page: 6.1	unhealthy, adult n = 568 Health Status: unhealthy Condition: thrombosis Age Group: adult Sex: unknown Population Size: 568 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2011/022485lbl.pdf Page: 6.1

Overview

CYP3A4	CYP2C9	CYP2D6	hERG
substrate 1737	substrate 1037	substrate 1217

OverviewOther

Other Inhibitor	Other Substrate	Other Inducer
	CYP3A 191 CYP1A2 1054 CYP2A6 543 CYP2C19 991 CYP2E1 667 CYP3A4/5 85 CYP4A9/11 5

Drug as victim

Target	Modality	Activity	Clinical evidence
CYP1A2 1054	substrate 3367 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2000/20-883_Acova_biopharmr_P1.pdf#page=34 Page: 34.0	no
CYP2A6 543	substrate 3367 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2000/20-883_Acova_biopharmr_P1.pdf#page=34 Page: 34.0	no
CYP2C19 991	substrate 3367 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2000/20-883_Acova_biopharmr_P1.pdf#page=34 Page: 34.0	no
CYP2C9 1037	substrate 3367 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2000/20-883_Acova_biopharmr_P1.pdf#page=34 Page: 34.0	no
CYP2D6 1217	substrate 3367 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2000/20-883_Acova_biopharmr_P1.pdf#page=34 Page: 34.0	no
CYP2E1 667	substrate 3367 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2000/20-883_Acova_biopharmr_P1.pdf#page=34 Page: 34.0	no
CYP4A9/11 5	substrate 3367 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2000/20-883_Acova_biopharmr_P1.pdf#page=34 Page: 34.0	no
CYP3A 191	substrate 3367 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2000/20-883_Acova_biopharmr_P1.pdf#page=34 Page: 34.0	yes
CYP3A4 1737	substrate 3367 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2000/20-883_Acova_biopharmr_P1.pdf#page=34 Page: 34.0	yes	no (co-administration study) Comment: In 10 healthy subjects, orally administered erythromycin (a potent inhibitor of CYP3A4/5) at 500 mg four times daily for 7 days had no effect on the pharmacokinetics of argatroban at a dose of 1 mcg/kg/min for 5 hours. These data suggest oxidative metabolism by CYP3A4/5 is not an important elimination pathway in-vivo for argatroban. Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2000/20-883_Acova_biopharmr_P1.pdf#page=34 Page: 34.0
CYP3A4/5 85	substrate 3367 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2000/20-883_Acova_biopharmr_P1.pdf#page=34 Page: 34.0	yes	no (co-administration study) Comment: In 10 healthy subjects, orally administered erythromycin (a potent inhibitor of CYP3A4/5) at 500 mg four times daily for 7 days had no effect on the pharmacokinetics of argatroban at a dose of 1 mcg/kg/min for 5 hours. These data suggest oxidative metabolism by CYP3A4/5 is not an important elimination pathway in-vivo for argatroban. Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2000/20-883_Acova_biopharmr_P1.pdf#page=34 Page: 34.0

Sourcing

Vendor/Aggregator	ID	URL
3B Scientific (Wuhan) Corp	3B2-0669	http://www.3bsc.com/index/pro_info.php?id=20025
AHH Chemical co.,ltd	API-1639	http://www.ahhchemical.com/product/API-1639.html
AK Scientific, Inc. (AKSCI)	2858AH	http://www.aksci.com/item_detail.php?cat=2858AH
AK Scientific, Inc. (AKSCI)	K280	http://www.aksci.com/item_detail.php?cat=K280
Aaron Chemicals	AR003950	http://www.aaronchem.com/74863-84-6
AbMole Bioscience	M3717	http://www.abmole.com/products/argatroban.html
Achemo Scientific Limited	AC-13286	http://www.achemo.com/search/?Keyword= 74863-84-6
Achemtek	0104-014000	http://www.achemtek.com/74863-84-6
Acorn PharmaTech	ACN-029030	http://www.acornpharmatech.com/
Allbio Pharm Co., Ltd	AD14276	http://www.allbiopharm.com/product/n/AD14276
Alsachim	4450	http://www.alsachim.com/product-C5781-glo.bal-view.html
Anward	ANW-47142	http://www.anward.com/pro_result/33593
Aurum Pharmatech LLC	S-7070	http://www.Aurumpharmatech.com/Product/ProductDetails/S_7070
AvaChem Scientific	2177	http://www.avachem.com/productSearch.asp?2177
BLD Pharm	BD212071	http://www.bldpharm.com/products/74863-84-6.html
BioChemPartner	BCP06831	http://www.biochempartner.com/74863-84-6-BCP06831
BioSynth	J-500992	https://www.biosynth.com/en/products/all-products/products/J-500992.html
BioSynth	J-500996	https://www.biosynth.com/en/products/all-products/products/J-500996.html
CSNpharm	CSN12734	https://www.csnpharm.com/products/argatroban.html
Chem Scene	CS-2441	http://www.chemscene.com/74863-84-6.html
ChemMol	49402560	http://www.chemmol.com/chemmol/49402560.html
ChemMol	99143618	http://www.chemmol.com/chemmol/99143618.html
Chemspace	CSSB00016995017	https://chem-space.com/CSSB00016995017
DC Chemicals	DCAPI1329	http://www.dcchemicals.com//product_show-Argatroban.html
Excenen	EX-A4276	https://www.excenen.com/searchresultlist.php?id=EX-A4276
Glentham Life Sciences	GP6176	http://www.glentham.com/products/product/GP6176/
Hairui	HR130367	http://www.hairuichem.com/en/product/74863-84-6.html
Lab Network	LN00189578	https://labnetwork.com/frontend-app/p/#!/moleculedetails/LN00189578
Matrix Scientific	90469	https://www.matrixscientific.com/090469.html
MedChem Express	HY-B0375	https://www.medchemexpress.com/argatroban.html
MolPort	MolPort-042-652-601	https://www.molport.com/shop/molecule-link/MolPort-042-652-601
OChem	846	http://www.ocheminc.com/index.php?act=psearch&pid=863A846
Oakwood	91960	http://www.oakwoodchemical.com/ProductsList.aspx?CategoryID=-2&txtSearch=77134&ExtHyperLink=1
Renno Tech	RL04842	http://www.rennotech.com/product_show.asp?id=5091
Smolecule	S519294	http://www.smolecule.com/products/s519294
TCI (Tokyo Chemical Industry)	A2705	http://www.tcichemicals.com/eshop/en/us/commodity/A2705/index.html
THE BioTek	bt-259970	https://www.thebiotek.com/product/inhibitors/bt-259970
THE BioTek	bt-460432	https://www.thebiotek.com/product/others/bt-460432
Tocris	1637	https://www.tocris.com/products/argatroban_1637
TripleBond	CA0140	http://www.triplebond-canada.com/prod/1102/
Wuhan Atomole Chemicals Co., Ltd.	AT-20554	http://www.atomole.com/en/products-view.asp?id=9722
Yuhao Chemical	SY0113	http://www.chemyuhao.com/74863-84-6?.html
eNovation Chemicals	D320127	http://www.enovationchem.com/productDetails.asp?productID=D320127
iChemical	EBD2201845	http://www.ichemical.com/products/74863-84-6.html?utm_source=PubChem&utm_medium=website&utm_campaign=product%20catalogs

PubMed

Title	Date	PubMed
Anticoagulation with Novastan (argatroban) in patients with heparin-induced thrombocytopenia and heparin-induced thrombocytopenia and thrombosis syndrome.	1997	9200347
Inhibition of collagen-induced platelet aggregation by argatroban in patients with acute cerebral infarction.	1997 Oct 15	9361377
The first report of successful carotid stent implant using argatroban anticoagulation in a patient with heparin-induced thrombocytopenia and thrombosis syndrome: a case report.	1998 Jan	9456166
Argatroban anticoagulant therapy in patients with heparin-induced thrombocytopenia.	2001 Apr 10	11294800
Postpartum coronary artery dissection complicated by heparin-induced thrombocytopenia and thrombosis.	2001 Mar	11269422
Severe argatroban-induced coagulopathy in a patient with a history of heparin-induced thrombocytopenia.	2004 Dec	15560992
Heparin-induced thrombocytopenia in patients administered heparin solely for hemodialysis.	2006	17050234
Argatroban tPA stroke study: study design and results in the first treated cohort.	2006 Aug	16908730
Heparin-induced thrombocytopenia: treatment options and special considerations.	2007 Apr	17381384
Risk factors for major bleeding in patients with heparin-induced thrombocytopenia treated with argatroban: a retrospective study.	2008 Dec	19057393
Bivalirudin.	2008 May	18449412
Reducing harm associated with anticoagulation: practical considerations of argatroban therapy in heparin-induced thrombocytopenia.	2009	19338378
Extremely low doses of lepirudin in a patient with heparin-induced thrombocytopenia, high bleeding risk and renal insufficiency.	2009 Aug	19519692
A report of outcomes after orthotopic liver transplant with allografts from heparin antibody-positive donors.	2009 Mar	19364306
Argatroban dosage requirements and outcomes in intensive care versus non-intensive care patients.	2009 Sep	19698012
Heparin induced thrombocytopenia and re-thrombosis associated with warfarin and fondaparinux in a child.	2009 Sep	19415734
Prolonged elevation of plasma argatroban in a cardiac transplant patient with a suspected history of heparin-induced thrombocytopenia with thrombosis.	2010 Apr	20003049
Identification of old drugs as potential inhibitors of HIV-1 integrase - human LEDGF/p75 interaction via molecular docking.	2012 Dec	22733274
Therapeutic administration of the direct thrombin inhibitor argatroban reduces hepatic inflammation in mice with established fatty liver disease.	2012 Oct	22841818
Use of argatroban and catheter-directed thrombolysis with alteplase in an oncology patient with heparin-induced thrombocytopenia with thrombosis.	2014 May 1	24733133

Patents

Sample Use Guides

In Vivo Use Guide

Initial Dosage: Before administering Argatroban, discontinue heparin therapy and obtain a baseline aPTT. The recommended initial dose of Argatroban for adult patients without hepatic impairment is 2 mcg/kg/min, administered as a continuous infusion

Route of Administration: Intravenous

In Vitro Use Guide

In the presence of 10 nM thrombomodulin (TM) argatroban (1 uM) prolonged clot lysis time and enhanced thrombin generation.

Name

Type

Language

ARGATROBAN ANHYDROUS

Common Name

English

argatroban [INN]

Common Name

English

ARGATROBAN [MI]

Common Name

English

2-PIPERIDINECARBOXYLIC ACID, 1-((2S)-5-((AMINOIMINOMETHYL)AMINO)-1-OXO-2-(((1,2,3,4-TETRAHYDRO-3-METHYL-8-QUINOLINYL)SULFONYL)AMINO)PENTYL)-4-METHYL-, (2R,4R)- ANHYDROUS

Common Name

English

(2R,4R)-4-METHYL-1-(N (SUP 2)-((1,2,3,4-TETRAHYDRO-3-METHYL-8-QUINOLYL)SULFONYL)-L-ARGINYL)PIPECOLIC ACID

Systematic Name

English

Argatroban [WHO-DD]

Common Name

English

2-PIPERIDINECARBOXYLIC ACID, 1-(5-((AMINOIMINOMETHYL)AMINO)-1-OXO-2-(((1,2,3,4-TETRAHYDRO-3-METHYL-8-QUINOLINYL)SULFONYL)AMINO)PENTYL)-4-METHYL-

Common Name

English

Classification Tree Code System Code

NDF-RT

N0000175980