Details of the Drug

General Information of Drug (ID: DMFI46A)

• Drug Name: Argatroban
• Synonyms: Acova; Argatrobanum; MMTQAP; MPQA; Novastan; Argatrobanum [Latin]; MITSUBISHI INHIBITOR; MCI 9038; MD 805; MD805; Argatroban (anhydrous); Argatroban [INN:JAN]; GN-1600; MCI-9038; MD-805; MQI-ARG-MCP; (2R,4R)-1-[(2S)-5-(diaminomethylideneamino)-2-[(3-methyl-1,2,3,4-tetrahydroquinolin-8-yl)sulfonylamino]pentanoyl]-4-methylpiperidine-2-carboxylic acid; (2R,4R)-1-[(2S)-5-(diaminomethylideneamino)-2-[[(3R)-3-methyl-1,2,3,4-tetrahydroquinolin-8-yl]sulfonylamino]pentanoyl]-4-methylpiperidine-2-carboxylic acid; (2R,4R)-1-[(2S)-5-(diaminomethylideneamino)-2-[[(3S)-3-methyl-1,2,3,4-tetrahydroquinolin-8-yl]sulfonylamino]pentanoyl]-4-methylpiperidine-2-carboxylic acid; (2R,4R)-1-[5-(diaminomethylideneamino)-2-[(3-methyl-1,2,3,4-tetrahydroquinolin-8-yl)sulfonylamino]pentanoyl]-4-methylpiperidine-2-carboxylic acid; (2R,4R)-4-Methyl-1-((S)-N(sup 2)-(((RS)-1,2,3,4-tetrahydro-3-methyl-8-quinolyl)sulfonyl)arginyl)pipecolic acid; (2R,4R)-4-Methyl-1[Nalpha-[(3-methyl-1,2,3,4-tetrahydro-8-quinolinyl)sulfonyl]-L-arginyl)]-2-piperadinecarboxylic acid; (2r,4r)-4-methyl-1-[n2-(3-methyl-1,2,3,4-tetrahydro-8-quinolinesulfonyl)-l-arginyl]-2-piperidinecarboxylic acid; 21R-Argatroban; 4-methyl-1-(N(2)-(3-methyl-1,2,3,4-tetrahydro-8-quinolinesulfonyl)-L-arginyl)-2-piperidinecarboxylic acid

Indication

Disease Entry	ICD 11	Status	REF
Thrombosis	DB61-GB90	Approved	[1], [2]

• Therapeutic Class: Anticoagulants
• Drug Type: Small molecular drug
• #Ro5 Violations (Lipinski): 1:
  Molecular Weight (mw); 508.6
  Topological Polar Surface Area (xlogp); 1.3
  Rotatable Bond Count (rotbonds); 9
  Hydrogen Bond Donor Count (hbonddonor); 5
  Hydrogen Bond Acceptor Count (hbondacc); 8
• ADMET Property:
  BDDCS Class: Biopharmaceutics Drug Disposition Classification System (BDDCS) Class 2: low solubility and high permeability [3]
  Bioavailability: The bioavailability of drug is 100% [4]
  Clearance: The drug present in the plasma can be removed from the body at the rate of 5 mL/min/kg [5]
  Elimination: 16% of drug is excreted from urine in the unchanged form [3]
  Half-life: The concentration or amount of drug in body reduced by one-half in 39 and 51 minutes [5]
  Metabolism: The drug is metabolized via the liver [4]
  Unbound Fraction: The unbound fraction of drug in plasma is 0.46% [5]
  Vd: The volume of distribution (Vd) of drug is 0.174 L/kg [6]
• Chemical Identifiers:
  Formula: C23H36N6O5S
  IUPAC Name: (2R,4R)-1-[(2S)-5-(diaminomethylideneamino)-2-[(3-methyl-1,2,3,4-tetrahydroquinolin-8-yl)sulfonylamino]pentanoyl]-4-methylpiperidine-2-carboxylic acid
  Canonical SMILES: C[C@@H]1CCN([C@H](C1)C(=O)O)C(=O)[C@H](CCCN=C(N)N)NS(=O)(=O)C2=CC=CC3=C2NCC(C3)C
  InChI: 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
  InChIKey: KXNPVXPOPUZYGB-IOVMHBDKSA-N
• Cross-matching ID:
  PubChem CID: 92722
  ChEBI ID: CHEBI:94385
  CAS Number: 74863-84-6
  DrugBank ID: DB00278
  TTD ID: D07UWV
  INTEDE ID: DR0132

Molecular Interaction Atlas of This Drug

Drug Therapeutic Target (DTT)

DTT Name	DTT ID	UniProt ID	MOA	REF
Coagulation factor IIa (F2)	TT6L509	THRB_HUMAN	Inhibitor	[7], [8], [9]

Drug-Metabolizing Enzyme (DME)

DME Name	DME ID	UniProt ID	MOA	REF
Cytochrome P450 3A4 (CYP3A4)	DE4LYSA	CP3A4_HUMAN	Substrate	[10]
Cytochrome P450 3A5 (CYP3A5)	DEIBDNY	CP3A5_HUMAN	Substrate	[10]

Molecular Expression Atlas of This Drug

• The Studied Disease: Thrombosis
• ICD Disease Classification: DB61-GB90

Molecule Name	Molecule Type	Gene Name	p-value	Fold-Change	Z-score
Cytochrome P450 3A5 (CYP3A5)	DME	CYP3A5	5.82E-01	-6.00E-02	-2.69E-01
Cytochrome P450 3A4 (CYP3A4)	DME	CYP3A4	9.85E-01	2.24E-02	7.33E-02

Drug-Drug Interaction (DDI) Information of This Drug

Coadministration of a Drug Treating the Same Disease as Argatroban

DDI Drug Name	DDI Drug ID	Severity	Mechanism	Disease	REF
Apixaban	DM89JLN	Major	Increased risk of bleeding by the combination of Argatroban and Apixaban.	Thrombosis [DB61-GB90]	[38]
Cangrelor	DM8JRH0	Major	Increased risk of bleeding by the combination of Argatroban and Cangrelor.	Thrombosis [DB61-GB90]	[38]
Brilinta	DMBR01X	Moderate	Increased risk of bleeding by the combination of Argatroban and Brilinta.	Thrombosis [DB61-GB90]	[38]
Clopidogrel	DMOL54H	Major	Increased risk of bleeding by the combination of Argatroban and Clopidogrel.	Thrombosis [DB61-GB90]	[39]

Coadministration of a Drug Treating the Disease Different from Argatroban (Comorbidity)

DDI Drug Name	DDI Drug ID	Severity	Mechanism	Comorbidity	REF
Cilostazol	DMZMSCT	Major	Increased risk of bleeding by the combination of Argatroban and Cilostazol.	Arterial occlusive disease [BD40]	[39]
Pentosan polysulfate	DM2HRKE	Moderate	Increased risk of bleeding by the combination of Argatroban and Pentosan polysulfate.	Chronic pain [MG30]	[40]
Phenylbutazone	DMAYL0T	Moderate	Increased risk of bleeding by the combination of Argatroban and Phenylbutazone.	Chronic pain [MG30]	[39]
Ketoprofen	DMRKXPT	Moderate	Increased risk of bleeding by the combination of Argatroban and Ketoprofen.	Chronic pain [MG30]	[39]
Levomilnacipran	DMV26S8	Moderate	Increased risk of bleeding by the combination of Argatroban and Levomilnacipran.	Chronic pain [MG30]	[41]
Anisindione	DM2C48U	Major	Increased risk of bleeding by the combination of Argatroban and Anisindione.	Coagulation defect [3B10]	[42]
Regorafenib	DMHSY1I	Major	Increased risk of bleeding by the combination of Argatroban and Regorafenib.	Colorectal cancer [2B91]	[38]
Intedanib	DMSTA36	Moderate	Increased risk of bleeding by the combination of Argatroban and Intedanib.	Colorectal cancer [2B91]	[43]
Ardeparin	DMYRX8B	Major	Increased risk of bleeding by the combination of Argatroban and Ardeparin.	Coronary thrombosis [BA43]	[44]
Danaparoid	DM6CLBN	Major	Increased risk of bleeding by the combination of Argatroban and Danaparoid.	Deep vein thrombosis [BD71]	[44]
Rivaroxaban	DMQMBZ1	Major	Increased risk of bleeding by the combination of Argatroban and Rivaroxaban.	Deep vein thrombosis [BD71]	[45]
Sertraline	DM0FB1J	Moderate	Increased risk of bleeding by the combination of Argatroban and Sertraline.	Depression [6A70-6A7Z]	[41]
Fluoxetine	DM3PD2C	Moderate	Increased risk of bleeding by the combination of Argatroban and Fluoxetine.	Depression [6A70-6A7Z]	[41]
Vilazodone	DM4LECQ	Moderate	Increased risk of bleeding by the combination of Argatroban and Vilazodone.	Depression [6A70-6A7Z]	[41]
Paroxetine	DM5PVQE	Moderate	Increased risk of bleeding by the combination of Argatroban and Paroxetine.	Depression [6A70-6A7Z]	[41]
Vortioxetine	DM6F1PU	Moderate	Increased risk of bleeding by the combination of Argatroban and Vortioxetine.	Depression [6A70-6A7Z]	[41]
Duloxetine	DM9BI7M	Moderate	Increased risk of bleeding by the combination of Argatroban and Duloxetine.	Depression [6A70-6A7Z]	[41]
Milnacipran	DMBFE74	Moderate	Increased risk of bleeding by the combination of Argatroban and Milnacipran.	Depression [6A70-6A7Z]	[41]
Desvenlafaxine	DMHD4PE	Moderate	Increased risk of bleeding by the combination of Argatroban and Desvenlafaxine.	Depression [6A70-6A7Z]	[41]
Clomipramine	DMINRKW	Moderate	Increased risk of bleeding by the combination of Argatroban and Clomipramine.	Depression [6A70-6A7Z]	[41]
Venlafaxine	DMR6QH0	Moderate	Increased risk of bleeding by the combination of Argatroban and Venlafaxine.	Depression [6A70-6A7Z]	[41]
Heme	DMGC287	Moderate	Increased risk of bleeding by the combination of Argatroban and Heme.	Discovery agent [N.A.]	[46]
Apigenin	DMI3491	Minor	Increased risk of bleeding by the combination of Argatroban and Apigenin.	Discovery agent [N.A.]	[47]
PMID28870136-Compound-49	DMTUC9E	Moderate	Increased risk of bleeding by the combination of Argatroban and PMID28870136-Compound-49.	Discovery agent [N.A.]	[48]
Fenfluramine	DM0762O	Moderate	Increased risk of bleeding by the combination of Argatroban and Fenfluramine.	Epilepsy/seizure [8A61-8A6Z]	[41]
Suprofen	DMKXJZ7	Moderate	Increased risk of bleeding by the combination of Argatroban and Suprofen.	Eye anterior segment structural developmental anomaly [LA11]	[49]
Mefenamic acid	DMK7HFI	Moderate	Increased risk of bleeding by the combination of Argatroban and Mefenamic acid.	Female pelvic pain [GA34]	[39]
Avapritinib	DMK2GZX	Major	Increased risk of bleeding by the combination of Argatroban and Avapritinib.	Gastrointestinal stromal tumour [2B5B]	[38]
Sulfinpyrazone	DMEV954	Major	Increased risk of bleeding by the combination of Argatroban and Sulfinpyrazone.	Gout [FA25]	[39]
Tipranavir	DM8HJX6	Major	Increased risk of bleeding by the combination of Argatroban and Tipranavir.	Human immunodeficiency virus disease [1C60-1C62]	[50]
Dipyridamole	DMXY30O	Major	Increased risk of bleeding by the combination of Argatroban and Dipyridamole.	Hypertension [BA00-BA04]	[39]
Meclofenamic acid	DM05FXR	Moderate	Increased risk of bleeding by the combination of Argatroban and Meclofenamic acid.	Inflammatory spondyloarthritis [FA92]	[39]
Acalabrutinib	DM7GCVW	Major	Increased risk of bleeding by the combination of Argatroban and Acalabrutinib.	Mature B-cell lymphoma [2A85]	[51]
Ibrutinib	DMHZCPO	Major	Increased risk of bleeding by the combination of Argatroban and Ibrutinib.	Mature B-cell lymphoma [2A85]	[52]
Ponatinib	DMYGJQO	Major	Increased risk of bleeding by the combination of Argatroban and Ponatinib.	Mature B-cell lymphoma [2A85]	[53]
Panobinostat	DM58WKG	Major	Increased risk of bleeding by the combination of Argatroban and Panobinostat.	Multiple myeloma [2A83]	[54]
Fedratinib	DM4ZBK6	Major	Increased risk of bleeding by the combination of Argatroban and Fedratinib.	Myeloproliferative neoplasm [2A20]	[39]
Dasatinib	DMJV2EK	Major	Increased risk of bleeding by the combination of Argatroban and Dasatinib.	Myeloproliferative neoplasm [2A20]	[55]
Omacetaxine mepesuccinate	DMPU2WX	Major	Increased risk of bleeding by the combination of Argatroban and Omacetaxine mepesuccinate.	Myeloproliferative neoplasm [2A20]	[40]
Prasugrel	DM7MT6E	Major	Increased risk of bleeding by the combination of Argatroban and Prasugrel.	Myocardial infarction [BA41-BA43]	[38]
Vorapaxar	DMA16BR	Major	Increased risk of bleeding by the combination of Argatroban and Vorapaxar.	Myocardial infarction [BA41-BA43]	[56]
Tirofiban	DMQG17S	Major	Increased risk of bleeding by the combination of Argatroban and Tirofiban.	Myocardial infarction [BA41-BA43]	[39]
Sibutramine	DMFJTDI	Moderate	Increased risk of bleeding by the combination of Argatroban and Sibutramine.	Obesity [5B80-5B81]	[41]
Dexfenfluramine	DMJ7YDS	Moderate	Increased risk of bleeding by the combination of Argatroban and Dexfenfluramine.	Obesity [5B80-5B81]	[41]
Diclofenac	DMPIHLS	Moderate	Increased risk of bleeding by the combination of Argatroban and Diclofenac.	Osteoarthritis [FA00-FA05]	[39]
Nepafenac	DMYK490	Moderate	Increased risk of bleeding by the combination of Argatroban and Nepafenac.	Osteoarthritis [FA00-FA05]	[49]
Naproxen	DMZ5RGV	Moderate	Increased risk of bleeding by the combination of Argatroban and Naproxen.	Osteoarthritis [FA00-FA05]	[39]
MK-4827	DMLYGH4	Moderate	Increased risk of bleeding by the combination of Argatroban and MK-4827.	Ovarian cancer [2C73]	[38]
Aspirin	DM672AH	Moderate	Increased risk of bleeding by the combination of Argatroban and Aspirin.	Pain [MG30-MG3Z]	[39]
Etodolac	DM6WJO9	Moderate	Increased risk of bleeding by the combination of Argatroban and Etodolac.	Pain [MG30-MG3Z]	[39]
Diflunisal	DM7EN8I	Moderate	Increased risk of bleeding by the combination of Argatroban and Diflunisal.	Pain [MG30-MG3Z]	[39]
Ibuprofen	DM8VCBE	Moderate	Increased risk of bleeding by the combination of Argatroban and Ibuprofen.	Pain [MG30-MG3Z]	[39]
Nabumetone	DMAT2XH	Moderate	Increased risk of bleeding by the combination of Argatroban and Nabumetone.	Pain [MG30-MG3Z]	[39]
Piroxicam	DMTK234	Moderate	Increased risk of bleeding by the combination of Argatroban and Piroxicam.	Pain [MG30-MG3Z]	[39]
Choline salicylate	DM8P137	Moderate	Increased risk of bleeding by the combination of Argatroban and Choline salicylate.	Postoperative inflammation [1A00-CA43]	[57]
Ketorolac	DMI4EL5	Moderate	Increased risk of bleeding by the combination of Argatroban and Ketorolac.	Postoperative inflammation [1A00-CA43]	[39]
Bromfenac	DMKB79O	Moderate	Increased risk of bleeding by the combination of Argatroban and Bromfenac.	Postoperative inflammation [1A00-CA43]	[39]
Treprostinil	DMTIQF3	Moderate	Increased risk of bleeding by the combination of Argatroban and Treprostinil.	Pulmonary hypertension [BB01]	[58]
Epoprostenol	DMUTYR2	Moderate	Increased risk of bleeding by the combination of Argatroban and Epoprostenol.	Pulmonary hypertension [BB01]	[58]
Iloprost	DMVPZBE	Moderate	Increased risk of bleeding by the combination of Argatroban and Iloprost.	Pulmonary hypertension [BB01]	[58]
Salsalate	DM13P4C	Moderate	Increased risk of bleeding by the combination of Argatroban and Salsalate.	Rheumatoid arthritis [FA20]	[57]
Meloxicam	DM2AR7L	Moderate	Increased risk of bleeding by the combination of Argatroban and Meloxicam.	Rheumatoid arthritis [FA20]	[39]
Sulindac	DM2QHZU	Moderate	Increased risk of bleeding by the combination of Argatroban and Sulindac.	Rheumatoid arthritis [FA20]	[39]
Oxaprozin	DM9UB0P	Moderate	Increased risk of bleeding by the combination of Argatroban and Oxaprozin.	Rheumatoid arthritis [FA20]	[39]
Flurbiprofen	DMGN4BY	Moderate	Increased risk of bleeding by the combination of Argatroban and Flurbiprofen.	Rheumatoid arthritis [FA20]	[39]
Fenoprofen	DML5VQ0	Moderate	Increased risk of bleeding by the combination of Argatroban and Fenoprofen.	Rheumatoid arthritis [FA20]	[39]
Indomethacin	DMSC4A7	Moderate	Increased risk of bleeding by the combination of Argatroban and Indomethacin.	Rheumatoid arthritis [FA20]	[39]
Tolmetin	DMWUIJE	Moderate	Increased risk of bleeding by the combination of Argatroban and Tolmetin.	Rheumatoid arthritis [FA20]	[39]
Salicyclic acid	DM2F8XZ	Moderate	Increased risk of bleeding by the combination of Argatroban and Salicyclic acid.	Seborrhoeic dermatitis [EA81]	[59]
Curcumin	DMQPH29	Minor	Increased risk of bleeding by the combination of Argatroban and Curcumin.	Solid tumour/cancer [2A00-2F9Z]	[60]
Warfarin	DMJYCVW	Major	Increased risk of bleeding by the combination of Argatroban and Warfarin.	Supraventricular tachyarrhythmia [BC81]	[42]
Caplacizumab	DMPUKA7	Major	Increased risk of bleeding by the combination of Argatroban and Caplacizumab.	Thrombocytopenia [3B64]	[54]
Cabozantinib	DMIYDT4	Major	Increased risk of bleeding by the combination of Argatroban and Cabozantinib.	Thyroid cancer [2D10]	[61]
Betrixaban	DM2C4RF	Major	Increased risk of bleeding by the combination of Argatroban and Betrixaban.	Venous thromboembolism [BD72]	[62]

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