Details of the Drug

General Information of Drug (ID: DMQG17S)

• Drug Name: Tirofiban
• Synonyms: AGG; Aggrastat; Agrastat; Tirofibanum; Aggrastat (TN); Agrastat (TN); L-700462; MK-383; Tirofiban (INN); Tirofiban[BAN:INN]; Tirofiban [INN:BAN]; L-700,462; N-(BUTYLSULFONYL)-O-[4-(4-PIPERIDINYL)BUTYL]-L-TYROSINE; N-(Butylsulfonyl)-O-(4-(4-piperidyl)butyl)-L-tyrosine; N-(butylsulfonyl)-O-(4-piperidin-4-ylbutyl)-L-tyrosine; N-(butylsulfonyl)-o-[4-(piperidin-4-yl)butyl]-l-tyrosine; (2S)-2-(butylsulfonylamino)-3-[4-(4-piperidin-4-ylbutoxy)phenyl]propanoic acid

Indication

Disease Entry	ICD 11	Status	REF
Acute coronary syndrome	BA41	Approved	[1]

• Therapeutic Class: Fibrinolytic Agents
• Drug Type: Small molecular drug
• #Ro5 Violations (Lipinski): 1:
  Molecular Weight (mw); 440.6
  Logarithm of the Partition Coefficient (xlogp); 1.4
  Rotatable Bond Count (rotbonds); 14
  Hydrogen Bond Donor Count (hbonddonor); 3
  Hydrogen Bond Acceptor Count (hbondacc); 7
• ADMET Property:
  BDDCS Class: Biopharmaceutics Drug Disposition Classification System (BDDCS) Class 3: high solubility and low permeability [2]
  Clearance: The drug present in the plasma can be removed from the body at the rate of 3 mL/min/kg [3]
  Elimination: 65% of drug is excreted from urine in the unchanged form [2]
  Half-life: The concentration or amount of drug in body reduced by one-half in 2 hours [3]
  Unbound Fraction: The unbound fraction of drug in plasma is 0.36% [3]
  Vd: The volume of distribution (Vd) of drug is 22-42 L []

Adverse Drug Reaction (ADR)

ADR Term	Variation	Related DOT	DOT ID	REF
Surgical and medical procedures	Not Available	ITGA2B	OT4Y17PY	[4]
Surgical and medical procedures	Not Available	ITGB3	OTWCK1K6	[4]

• Chemical Identifiers:
  Formula: C22H36N2O5S
  IUPAC Name: (2S)-2-(butylsulfonylamino)-3-[4-(4-piperidin-4-ylbutoxy)phenyl]propanoic acid
  Canonical SMILES: CCCCS(=O)(=O)N[C@@H](CC1=CC=C(C=C1)OCCCCC2CCNCC2)C(=O)O
  InChI: InChI=1S/C22H36N2O5S/c1-2-3-16-30(27,28)24-21(22(25)26)17-19-7-9-20(10-8-19)29-15-5-4-6-18-11-13-23-14-12-18/h7-10,18,21,23-24H,2-6,11-17H2,1H3,(H,25,26)/t21-/m0/s1
  InChIKey: COKMIXFXJJXBQG-NRFANRHFSA-N
• Cross-matching ID:
  PubChem CID: 60947
  ChEBI ID: CHEBI:9605
  CAS Number: 144494-65-5
  DrugBank ID: DB00775
  TTD ID: D0BN9X

Molecular Interaction Atlas of This Drug

Drug Therapeutic Target (DTT)

DTT Name	DTT ID	UniProt ID	MOA	REF
Glycoprotein IIb/IIIa receptor (GPIIb/IIIa)	TT38RM1	ITA2B_HUMAN ; ITB3_HUMAN	Modulator	[5]

Drug Off-Target (DOT)

DOT Name	DOT ID	UniProt ID	Interaction	REF
Integrin alpha-IIb (ITGA2B)	OT4Y17PY	ITA2B_HUMAN	Drug Response	[4]
Integrin beta-3 (ITGB3)	OTWCK1K6	ITB3_HUMAN	Drug Response	[4]

Molecular Expression Atlas of This Drug

• The Studied Disease: Acute coronary syndrome
• ICD Disease Classification: BA41

Molecule Name	Molecule Type	Gene Name	p-value	Fold-Change	Z-score
Glycoprotein IIb/IIIa receptor (GPIIb/IIIa)	DTT	ITGA2B; ITGB3	7.83E-01	-0.11	-0.45

Drug-Drug Interaction (DDI) Information of This Drug

Coadministration of a Drug Treating the Same Disease as Tirofiban

DDI Drug Name	DDI Drug ID	Severity	Mechanism	Disease	REF
Prasugrel	DM7MT6E	Major	Increased risk of bleeding by the combination of Tirofiban and Prasugrel.	Myocardial infarction [BA41-BA43]	[6]
Vorapaxar	DMA16BR	Major	Increased risk of bleeding by the combination of Tirofiban and Vorapaxar.	Myocardial infarction [BA41-BA43]	[7]

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

DDI Drug Name	DDI Drug ID	Severity	Mechanism	Comorbidity	REF
Phenylbutazone	DMAYL0T	Moderate	Increased risk of bleeding by the combination of Tirofiban and Phenylbutazone.	Chronic pain [MG30]	[8]
Ketoprofen	DMRKXPT	Moderate	Increased risk of bleeding by the combination of Tirofiban and Ketoprofen.	Chronic pain [MG30]	[8]
Levomilnacipran	DMV26S8	Moderate	Increased risk of bleeding by the combination of Tirofiban and Levomilnacipran.	Chronic pain [MG30]	[9]
Anisindione	DM2C48U	Major	Increased risk of bleeding by the combination of Tirofiban and Anisindione.	Coagulation defect [3B10]	[8]
Regorafenib	DMHSY1I	Major	Increased risk of bleeding by the combination of Tirofiban and Regorafenib.	Colorectal cancer [2B91]	[10]
Intedanib	DMSTA36	Moderate	Increased risk of bleeding by the combination of Tirofiban and Intedanib.	Colorectal cancer [2B91]	[11]
Ardeparin	DMYRX8B	Major	Increased risk of bleeding by the combination of Tirofiban and Ardeparin.	Coronary thrombosis [BA43]	[12]
Danaparoid	DM6CLBN	Major	Increased risk of bleeding by the combination of Tirofiban and Danaparoid.	Deep vein thrombosis [BD71]	[12]
Rivaroxaban	DMQMBZ1	Major	Increased risk of bleeding by the combination of Tirofiban and Rivaroxaban.	Deep vein thrombosis [BD71]	[13]
Sertraline	DM0FB1J	Moderate	Increased risk of bleeding by the combination of Tirofiban and Sertraline.	Depression [6A70-6A7Z]	[9]
Vilazodone	DM4LECQ	Moderate	Increased risk of bleeding by the combination of Tirofiban and Vilazodone.	Depression [6A70-6A7Z]	[9]
Vortioxetine	DM6F1PU	Moderate	Increased risk of bleeding by the combination of Tirofiban and Vortioxetine.	Depression [6A70-6A7Z]	[9]
Milnacipran	DMBFE74	Moderate	Increased risk of bleeding by the combination of Tirofiban and Milnacipran.	Depression [6A70-6A7Z]	[9]
Escitalopram	DMFK9HG	Moderate	Increased risk of bleeding by the combination of Tirofiban and Escitalopram.	Depression [6A70-6A7Z]	[9]
Desvenlafaxine	DMHD4PE	Moderate	Increased risk of bleeding by the combination of Tirofiban and Desvenlafaxine.	Depression [6A70-6A7Z]	[9]
Clomipramine	DMINRKW	Moderate	Increased risk of bleeding by the combination of Tirofiban and Clomipramine.	Depression [6A70-6A7Z]	[9]
Heme	DMGC287	Moderate	Increased risk of bleeding by the combination of Tirofiban and Heme.	Discovery agent [N.A.]	[14]
Apigenin	DMI3491	Minor	Increased risk of bleeding by the combination of Tirofiban and Apigenin.	Discovery agent [N.A.]	[15]
PMID28870136-Compound-49	DMTUC9E	Moderate	Increased risk of bleeding by the combination of Tirofiban and PMID28870136-Compound-49.	Discovery agent [N.A.]	[16]
Suprofen	DMKXJZ7	Moderate	Increased risk of bleeding by the combination of Tirofiban and Suprofen.	Eye anterior segment structural developmental anomaly [LA11]	[17]
Avapritinib	DMK2GZX	Major	Increased risk of bleeding by the combination of Tirofiban and Avapritinib.	Gastrointestinal stromal tumour [2B5B]	[10]
Tipranavir	DM8HJX6	Major	Increased risk of bleeding by the combination of Tirofiban and Tipranavir.	Human immunodeficiency virus disease [1C60-1C62]	[18]
Dipyridamole	DMXY30O	Major	Increased risk of bleeding by the combination of Tirofiban and Dipyridamole.	Hypertension [BA00-BA04]	[6]
Meclofenamic acid	DM05FXR	Moderate	Increased risk of bleeding by the combination of Tirofiban and Meclofenamic acid.	Inflammatory spondyloarthritis [FA92]	[8]
Acalabrutinib	DM7GCVW	Major	Increased risk of bleeding by the combination of Tirofiban and Acalabrutinib.	Mature B-cell lymphoma [2A85]	[19]
Ibrutinib	DMHZCPO	Major	Increased risk of bleeding by the combination of Tirofiban and Ibrutinib.	Mature B-cell lymphoma [2A85]	[20]
Ponatinib	DMYGJQO	Major	Increased risk of bleeding by the combination of Tirofiban and Ponatinib.	Mature B-cell lymphoma [2A85]	[21]
Panobinostat	DM58WKG	Major	Increased risk of bleeding by the combination of Tirofiban and Panobinostat.	Multiple myeloma [2A83]	[22]
Dasatinib	DMJV2EK	Major	Increased risk of bleeding by the combination of Tirofiban and Dasatinib.	Myeloproliferative neoplasm [2A20]	[23]
Omacetaxine mepesuccinate	DMPU2WX	Major	Increased risk of bleeding by the combination of Tirofiban and Omacetaxine mepesuccinate.	Myeloproliferative neoplasm [2A20]	[24]
Sibutramine	DMFJTDI	Moderate	Increased risk of bleeding by the combination of Tirofiban and Sibutramine.	Obesity [5B80-5B81]	[9]
Dexfenfluramine	DMJ7YDS	Moderate	Increased risk of bleeding by the combination of Tirofiban and Dexfenfluramine.	Obesity [5B80-5B81]	[9]
Nepafenac	DMYK490	Moderate	Increased risk of bleeding by the combination of Tirofiban and Nepafenac.	Osteoarthritis [FA00-FA05]	[17]
Naproxen	DMZ5RGV	Moderate	Increased risk of bleeding by the combination of Tirofiban and Naproxen.	Osteoarthritis [FA00-FA05]	[8]
MK-4827	DMLYGH4	Moderate	Increased risk of bleeding by the combination of Tirofiban and MK-4827.	Ovarian cancer [2C73]	[10]
Aspirin	DM672AH	Moderate	Increased risk of bleeding by the combination of Tirofiban and Aspirin.	Pain [MG30-MG3Z]	[25]
Diflunisal	DM7EN8I	Moderate	Increased risk of bleeding by the combination of Tirofiban and Diflunisal.	Pain [MG30-MG3Z]	[25]
Ibuprofen	DM8VCBE	Moderate	Increased risk of bleeding by the combination of Tirofiban and Ibuprofen.	Pain [MG30-MG3Z]	[8]
Choline salicylate	DM8P137	Moderate	Increased risk of bleeding by the combination of Tirofiban and Choline salicylate.	Postoperative inflammation [1A00-CA43]	[25]
Bromfenac	DMKB79O	Moderate	Increased risk of bleeding by the combination of Tirofiban and Bromfenac.	Postoperative inflammation [1A00-CA43]	[17]
Epoprostenol	DMUTYR2	Moderate	Increased risk of bleeding by the combination of Tirofiban and Epoprostenol.	Pulmonary hypertension [BB01]	[26]
Iloprost	DMVPZBE	Moderate	Increased risk of bleeding by the combination of Tirofiban and Iloprost.	Pulmonary hypertension [BB01]	[26]
Salsalate	DM13P4C	Moderate	Increased risk of bleeding by the combination of Tirofiban and Salsalate.	Rheumatoid arthritis [FA20]	[25]
Meloxicam	DM2AR7L	Moderate	Increased risk of bleeding by the combination of Tirofiban and Meloxicam.	Rheumatoid arthritis [FA20]	[8]
Oxaprozin	DM9UB0P	Moderate	Increased risk of bleeding by the combination of Tirofiban and Oxaprozin.	Rheumatoid arthritis [FA20]	[8]
Salicyclic acid	DM2F8XZ	Moderate	Increased risk of bleeding by the combination of Tirofiban and Salicyclic acid.	Seborrhoeic dermatitis [EA81]	[25]
Curcumin	DMQPH29	Minor	Increased risk of bleeding by the combination of Tirofiban and Curcumin.	Solid tumour/cancer [2A00-2F9Z]	[27]
Caplacizumab	DMPUKA7	Major	Increased risk of bleeding by the combination of Tirofiban and Caplacizumab.	Thrombocytopenia [3B64]	[22]
Apixaban	DM89JLN	Major	Increased risk of bleeding by the combination of Tirofiban and Apixaban.	Thrombosis [DB61-GB90]	[10]
Cangrelor	DM8JRH0	Major	Increased risk of bleeding by the combination of Tirofiban and Cangrelor.	Thrombosis [DB61-GB90]	[10]
Brilinta	DMBR01X	Moderate	Increased risk of bleeding by the combination of Tirofiban and Brilinta.	Thrombosis [DB61-GB90]	[10]
Cabozantinib	DMIYDT4	Major	Increased risk of bleeding by the combination of Tirofiban and Cabozantinib.	Thyroid cancer [2D10]	[28]
Betrixaban	DM2C4RF	Major	Increased risk of bleeding by the combination of Tirofiban and Betrixaban.	Venous thromboembolism [BD72]	[29]

References

• [1] URL: http://www.guidetopharmacology.org Nucleic Acids Res. 2015 Oct 12. pii: gkv1037. The IUPHAR/BPS Guide to PHARMACOLOGY in 2016: towards curated quantitative interactions between 1300 protein targets and 6000 ligands. (Ligand id: 6586).
• [2] BDDCS applied to over 900 drugs
• [3] Trend Analysis of a Database of Intravenous Pharmacokinetic Parameters in Humans for 1352 Drug Compounds
• [4] ADReCS-Target: target profiles for aiding drug safety research and application. Nucleic Acids Res. 2018 Jan 4;46(D1):D911-D917. doi: 10.1093/nar/gkx899.
• [5] Drugs@FDA. U.S. Food and Drug Administration. U.S. Department of Health & Human Services.
• [6] Klinkhardt U, Kirchmaier CM, Westrup D, Graff J, Mahnel R, Breddin HK, Harder S "Ex vivo-in vitro interaction between aspirin, clopidogrel, and the glycoprotein IIb/IIIa inhibitors abciximab and SR121566A." Clin Pharmacol Ther 67 (2000): 305-13. [PMID: 10741635]
• [7] Product Information. Zontivity (vorapaxar). Merck & Company Inc, Whitehouse Station, NJ.
• [8] Product Information. Integrilin (eptifibatide). Schering Laboratories, Kenilworth, NJ.
• [9] Alderman CP, Moritz CK, Ben-Tovim DI "Abnormal platelet aggregation associated with fluoxetine therapy." Ann Pharmacother 26 (1992): 1517-9. [PMID: 1482806]
• [10] Cerner Multum, Inc. "UK Summary of Product Characteristics.".
• [11] Product Information. Ofev (nintedanib). Boehringer Ingelheim, Ridgefield, CT.
• [12] Price AJ, Frcpath DO "Is there a clinical interaction between low molecular weight heparin and non-steroidal analgesics after total hip replacement?" Ann R Coll Surg Engl 77 (1995): 395. [PMID: 7486773]
• [13] Product Information. Xarelto (rivaroxaban). Bayer Inc, Toronto, IA.
• [14] Product Information. Panhematin (hemin). Recordati Rare Diseases Inc, Lebanon, NJ.
• [15] Heck AM, DeWitt BA, Lukes AL "Potential interactions between alternative therapies and warfarin." Am J Health Syst Pharm 57 (2000): 1221-7 quiz 1228-30. [PMID: 10902065]
• [16] Canadian Pharmacists Association.
• [17] Product Information. Acular (ketorolac). Allergan Inc, Irvine, CA.
• [18] Product Information. Aptivus (tipranavir). Boehringer-Ingelheim, Ridgefield, CT.
• [19] Product Information. Calquence (acalabrutinib). Astra-Zeneca Pharmaceuticals, Wilmington, DE.
• [20] Agencia Espaola de Medicamentos y Productos Sanitarios Healthcare "Centro de informacion online de medicamentos de la AEMPS - CIMA.".
• [21] Product Information. Iclusig (ponatinib). Ariad Pharmaceuticals Inc, Cambridge, MA.
• [22] Cerner Multum, Inc. "Australian Product Information.".
• [23] Product Information. Sprycel (dasatinib). Bristol-Myers Squibb, Princeton, NJ.
• [24] Product Information. Brukinsa (zanubrutinib). BeiGene USA, Inc, San Mateo, CA.
• [25] Hirsch J, Dalen J, Guyatt G, American College of Chest Physicians "The sixth (2000) ACCP guidelines for antithrombotic therapy for prevention and treatment of thrombosis. American College of Physicians." Chest 119(1 Suppl) (2001): 1S-2S. [PMID: 11157638]
• [26] Product Information. Flolan (epoprostenol). Glaxo Wellcome, Research Triangle Park, NC.
• [27] Abebe W "Herbal medication: potential for adverse interactions with analgesic drugs." J Clin Pharm Ther 27 (2002): 391-401. [PMID: 12472978]
• [28] Product Information. Cometriq (cabozantinib). Exelixis Inc, S San Francisco, CA.
• [29] Product Information. Bevyxxa (betrixaban). Portola Pharmaceuticals, South San Francisco, CA.