Details of the Drug

General Information of Drug (ID: DMVRIC2)

Drug Name

Zileuton

Synonyms

Leutrol; Zileutonum; Ziluton; Zyflo; Abbott brand of zileuton; Zyflo CR; Zyflo Filmtab; A 64077; Abbot 64077; Abbott 64077; A-64077; ABBOTT-64077; ABT-077; CTI-02; ZYFLO (TN); ZYFLO, Zileuton; Zileutonum [INN-Latin]; Zyflo (TN); Zileuton (USP/INN); Zileuton [USAN:INN:BAN]; N-[1-(benzo[b]thiophen-2-yl)ethyl]-N-hydroxyurea; N-(1-Benzo(b)thien-2-ylethyl)-N-hydroxyurea; (+-)-1-(1-Benzo(b)thien-2-ylethyl)-1-hydroxyurea; (+-)-1-(1-Benzo[b]thien-2-ylethyl)-1-hydroxyurea; (+/-)-1-(1-Benzo[b]thien-2-ylethyl)-1-hydroxyurea; 1-[1-(1-benzothien-2-yl)ethyl]-1-hydroxyurea; 1-[1-(1-benzothiophen-2-yl)ethyl]-1-hydroxyurea

Indication

Disease Entry	ICD 11	Status	REF
Allergic asthma	CA23.0	Approved	[1]
Asthma	CA23	Approved	[2]
Intrinsic asthma	N.A.	Approved	[1]
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Therapeutic Class

Antiinflammatory Agents

Drug Type

Small molecular drug

Structure

3D MOL

2D MOL

#Ro5 Violations (Lipinski): 0

Molecular Weight (mw)

236.29

Logarithm of the Partition Coefficient (xlogp)

1.6

Rotatable Bond Count (rotbonds)

Hydrogen Bond Donor Count (hbonddonor)

Hydrogen Bond Acceptor Count (hbondacc)

ADMET Property

Absorption: The drug is rapidly and almost completely absorbed []
BDDCS Class: Biopharmaceutics Drug Disposition Classification System (BDDCS) Class 2: low solubility and high permeability [3]
Clearance: The apparent oral clearance of drug is 7 mL/min/kg []
Half-life: The concentration or amount of drug in body reduced by one-half in 2.5 hours [4]
Metabolism: The drug is metabolized via the hepatic []
MRTD: The Maximum Recommended Therapeutic Dose (MRTD) of drug that ensured maximising efficacy and moderate side effect is 169.28029 micromolar/kg/day [5]
Vd: The volume of distribution (Vd) of drug is 1.2 L/kg []
Water Solubility: The ability of drug to dissolve in water is measured as 0.5 mg/mL [3]

Chemical Identifiers

Formula: C11H12N2O2S
IUPAC Name: 1-[1-(1-benzothiophen-2-yl)ethyl]-1-hydroxyurea
Canonical SMILES: CC(C1=CC2=CC=CC=C2S1)N(C(=O)N)O
InChI: InChI=1S/C11H12N2O2S/c1-7(13(15)11(12)14)10-6-8-4-2-3-5-9(8)16-10/h2-7,15H,1H3,(H2,12,14)
InChIKey: MWLSOWXNZPKENC-UHFFFAOYSA-N

Cross-matching ID

PubChem CID: 60490
ChEBI ID: CHEBI:10112
CAS Number: 111406-87-2
DrugBank ID: DB00744
TTD ID: D09JUG
INTEDE ID: DR1730
ACDINA ID: D00740

Combinatorial Drugs (CBD)

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Repurposed Drugs (RPD)

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Molecular Interaction Atlas of This Drug

Drug Therapeutic Target (DTT)

DTT Name	DTT ID	UniProt ID	MOA	REF
Arachidonate 5-lipoxygenase (5-LOX)	TT2J34L	LOX5_HUMAN	Inhibitor	[6]

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Drug-Metabolizing Enzyme (DME)

DME Name	DME ID	UniProt ID	MOA	REF
Cytochrome P450 3A4 (CYP3A4)_{Main DME}	DE4LYSA	CP3A4_HUMAN	Substrate	[7]
Cytochrome P450 2C9 (CYP2C9)_{Main DME}	DE5IED8	CP2C9_HUMAN	Substrate	[8]
Cytochrome P450 1A2 (CYP1A2)_{Main DME}	DEJGDUW	CP1A2_HUMAN	Substrate	[9]
Prostaglandin G/H synthase 1 (COX-1)	DE073H6	PGH1_HUMAN	Substrate	[7]
UDP-glucuronosyltransferase 1A9 (UGT1A9)	DE85D2P	UD19_HUMAN	Substrate	[7]

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Drug Off-Target (DOT)

DOT Name	DOT ID	UniProt ID	Interaction	REF
11-beta-hydroxysteroid dehydrogenase type 2 (HSD11B2)	OTHF4H9U	DHI2_HUMAN	Gene/Protein Processing	[10]
Caspase-3 (CASP3)	OTIJRBE7	CASP3_HUMAN	Gene/Protein Processing	[11]
Caspase-7 (CASP7)	OTAPJ040	CASP7_HUMAN	Gene/Protein Processing	[11]
Cytochrome P450 1A2 (CYP1A2)	OTLLBX48	CP1A2_HUMAN	Gene/Protein Processing	[12]
Cytochrome P450 3A4 (CYP3A4)	OTQGYY83	CP3A4_HUMAN	Gene/Protein Processing	[13]
Interleukin-6 (IL6)	OTUOSCCU	IL6_HUMAN	Protein Interaction/Cellular Processes	[14]
Multidrug resistance-associated protein 1 (ABCC1)	OTGUN89S	MRP1_HUMAN	Drug Response	[15]
Polyunsaturated fatty acid 5-lipoxygenase (ALOX5)	OT7FOIK2	LOX5_HUMAN	Gene/Protein Processing	[10]

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Molecular Interaction Atlas (MIA)

MIA Detail

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Molecular Expression Atlas of This Drug

The Studied Disease

Allergic asthma

ICD Disease Classification

CA23.0

Molecule Name	Molecule Type	Gene Name	p-value	Fold-Change	Z-score
Arachidonate 5-lipoxygenase (5-LOX)	DTT	ALOX5	1.00E-02	0.55	2.11
Cytochrome P450 1A2 (CYP1A2)	DME	CYP1A2	7.68E-02	-2.10E-01	-6.42E-01
Cytochrome P450 2C9 (CYP2C9)	DME	CYP2C9	4.28E-02	-1.99E-01	-6.09E-01
Cytochrome P450 3A4 (CYP3A4)	DME	CYP3A4	9.81E-01	2.72E-01	6.95E-01
Prostaglandin G/H synthase 1 (COX-1)	DME	PTGS1	7.25E-01	-4.31E-02	-5.74E-02

Molecular Expression Atlas (MEA)

MEA Detail

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Drug-Drug Interaction (DDI) Information of This Drug

Coadministration of a Drug Treating the Same Disease as Zileuton

DDI Drug Name	DDI Drug ID	Severity	Mechanism	Disease	REF
Aminophylline	DML2NIB	Moderate	Decreased metabolism of Zileuton caused by Aminophylline mediated inhibition of CYP450 enzyme.	Asthma [CA23]	[16]
Roflumilast	DMPGHY8	Moderate	Decreased metabolism of Zileuton caused by Roflumilast mediated inhibition of CYP450 enzyme.	Asthma [CA23]	[17]
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Coadministration of a Drug Treating the Disease Different from Zileuton (Comorbidity)

DDI Drug Name	DDI Drug ID	Severity	Mechanism	Comorbidity	REF
Arn-509	DMT81LZ	Moderate	Increased metabolism of Zileuton caused by Arn-509 mediated induction of CYP450 enzyme.	Acute myeloid leukaemia [2A60]	[17]
Bepridil	DM0RKS4	Minor	Decreased metabolism of Zileuton caused by Bepridil mediated inhibition of CYP450 enzyme.	Angina pectoris [BA40]	[18]
Nifedipine	DMSVOZT	Minor	Decreased metabolism of Zileuton caused by Nifedipine mediated inhibition of CYP450 enzyme.	Angina pectoris [BA40]	[18]
Bedaquiline	DM3906J	Moderate	Increased risk of hepatotoxicity by the combination of Zileuton and Bedaquiline.	Antimicrobial drug resistance [MG50-MG52]	[19]
Obeticholic acid	DM3Q1SM	Moderate	Decreased metabolism of Zileuton caused by Obeticholic acid mediated inhibition of CYP450 enzyme.	Autoimmune liver disease [DB96]	[20]
Dalfopristin	DM4LTKV	Moderate	Decreased metabolism of Zileuton caused by Dalfopristin mediated inhibition of CYP450 enzyme.	Bacterial infection [1A00-1C4Z]	[21]
Telithromycin	DMZ4P3A	Moderate	Decreased metabolism of Zileuton caused by Telithromycin mediated inhibition of CYP450 enzyme.	Bacterial infection [1A00-1C4Z]	[22]
Pexidartinib	DMS2J0Z	Major	Increased risk of hepatotoxicity by the combination of Zileuton and Pexidartinib.	Bone/articular cartilage neoplasm [2F7B]	[23]
Lapatinib	DM3BH1Y	Moderate	Decreased metabolism of Zileuton caused by Lapatinib mediated inhibition of CYP450 enzyme.	Breast cancer [2C60-2C6Y]	[24]
Tucatinib	DMBESUA	Moderate	Decreased metabolism of Zileuton caused by Tucatinib mediated inhibition of CYP450 enzyme.	Breast cancer [2C60-2C6Y]	[25]
Alpelisib	DMEXMYK	Moderate	Increased metabolism of Zileuton caused by Alpelisib mediated induction of CYP450 enzyme.	Breast cancer [2C60-2C6Y]	[26]
Levobupivacaine	DM783CH	Moderate	Decreased metabolism of Zileuton caused by Levobupivacaine mediated inhibition of CYP450 enzyme.	Corneal disease [9A76-9A78]	[17]
Oxtriphylline	DMLHSE3	Moderate	Decreased metabolism of Zileuton caused by Oxtriphylline mediated inhibition of CYP450 enzyme.	Cough [MD12]	[16]
Mifepristone	DMGZQEF	Moderate	Decreased metabolism of Zileuton caused by Mifepristone mediated inhibition of CYP450 enzyme.	Cushing syndrome [5A70]	[27]
Osilodrostat	DMIJC9X	Moderate	Decreased metabolism of Zileuton caused by Osilodrostat mediated inhibition of CYP450 enzyme.	Cushing syndrome [5A70]	[28]
Ivacaftor	DMZC1HS	Moderate	Decreased metabolism of Zileuton caused by Ivacaftor mediated inhibition of CYP450 enzyme.	Cystic fibrosis [CA25]	[29]
Nefazodone	DM4ZS8M	Moderate	Decreased metabolism of Zileuton caused by Nefazodone mediated inhibition of CYP450 enzyme.	Depression [6A70-6A7Z]	[30]
PMID28870136-Compound-49	DMTUC9E	Moderate	Decreased metabolism of Zileuton caused by PMID28870136-Compound-49 mediated inhibition of CYP450 enzyme.	Discovery agent [N.A.]	[31]
Cenobamate	DM8KLU9	Moderate	Increased metabolism of Zileuton caused by Cenobamate mediated induction of CYP450 enzyme.	Epilepsy/seizure [8A61-8A6Z]	[32]
Stiripentol	DMMSDOY	Moderate	Decreased metabolism of Zileuton caused by Stiripentol mediated inhibition of CYP450 enzyme.	Epilepsy/seizure [8A61-8A6Z]	[17]
Cannabidiol	DM0659E	Moderate	Increased risk of hepatotoxicity by the combination of Zileuton and Cannabidiol.	Epileptic encephalopathy [8A62]	[17]
Itraconazole	DMCR1MV	Moderate	Decreased metabolism of Zileuton caused by Itraconazole mediated inhibition of CYP450 enzyme.	Fungal infection [1F29-1F2F]	[33]
Carvedilol	DMHTEAO	Moderate	Decreased metabolism of Zileuton caused by Carvedilol.	Heart failure [BD10-BD1Z]	[18]
Rifapentine	DMCHV4I	Moderate	Increased metabolism of Zileuton caused by Rifapentine mediated induction of CYP450 enzyme.	HIV-infected patients with tuberculosis [1B10-1B14]	[34]
Saquinavir	DMG814N	Moderate	Decreased metabolism of Zileuton caused by Saquinavir mediated inhibition of CYP450 enzyme.	Human immunodeficiency virus disease [1C60-1C62]	[35]
Etravirine	DMGV8QU	Moderate	Increased metabolism of Zileuton caused by Etravirine mediated induction of CYP450 enzyme.	Human immunodeficiency virus disease [1C60-1C62]	[36]
Mipomersen	DMGSRN1	Major	Increased risk of hepatotoxicity by the combination of Zileuton and Mipomersen.	Hyper-lipoproteinaemia [5C80]	[37]
Teriflunomide	DMQ2FKJ	Major	Increased risk of hepatotoxicity by the combination of Zileuton and Teriflunomide.	Hyper-lipoproteinaemia [5C80]	[38]
BMS-201038	DMQTAGO	Major	Increased risk of hepatotoxicity by the combination of Zileuton and BMS-201038.	Hyper-lipoproteinaemia [5C80]	[39]
Acebutolol	DM0TI4U	Moderate	Decreased metabolism of Zileuton caused by Acebutolol.	Hypertension [BA00-BA04]	[18]
Penbutolol	DM4ES8F	Moderate	Decreased metabolism of Zileuton caused by Penbutolol.	Hypertension [BA00-BA04]	[18]
Nebivolol	DM7F1PA	Moderate	Decreased metabolism of Zileuton caused by Nebivolol.	Hypertension [BA00-BA04]	[18]
Levamlodipine	DM92S6N	Minor	Decreased metabolism of Zileuton caused by Levamlodipine mediated inhibition of CYP450 enzyme.	Hypertension [BA00-BA04]	[18]
Pindolol	DMD2NV7	Moderate	Decreased metabolism of Zileuton caused by Pindolol.	Hypertension [BA00-BA04]	[18]
Conivaptan	DM1V329	Moderate	Decreased metabolism of Zileuton caused by Conivaptan mediated inhibition of CYP450 enzyme.	Hypo-osmolality/hyponatraemia [5C72]	[40]
Pirfenidone	DM6VZFQ	Moderate	Decreased metabolism of Zileuton caused by Pirfenidone mediated inhibition of CYP450 enzyme.	Idiopathic interstitial pneumonitis [CB03]	[17]
Givosiran	DM5PFIJ	Moderate	Decreased metabolism of Zileuton caused by Givosiran mediated inhibition of CYP450 enzyme.	Inborn porphyrin/heme metabolism error [5C58]	[41]
Berotralstat	DMWA2DZ	Moderate	Decreased metabolism of Zileuton caused by Berotralstat mediated inhibition of CYP450 enzyme.	Innate/adaptive immunodeficiency [4A00]	[42]
Ramelteon	DM7IW9J	Moderate	Decreased metabolism of Zileuton caused by Ramelteon mediated inhibition of CYP450 enzyme.	Insomnia [7A00-7A0Z]	[43]
Tasimelteon	DMLOQ1V	Moderate	Decreased metabolism of Zileuton caused by Tasimelteon mediated inhibition of CYP450 enzyme.	Insomnia [7A00-7A0Z]	[44]
Alosetron	DML2A03	Moderate	Decreased metabolism of Zileuton caused by Alosetron mediated inhibition of CYP450 enzyme.	Irritable bowel syndrome [DD91]	[45]
Brigatinib	DM7W94S	Moderate	Increased metabolism of Zileuton caused by Brigatinib mediated induction of CYP450 enzyme.	Lung cancer [2C25]	[46]
PF-06463922	DMKM7EW	Moderate	Increased metabolism of Zileuton caused by PF-06463922 mediated induction of CYP450 enzyme.	Lung cancer [2C25]	[47]
Osimertinib	DMRJLAT	Moderate	Increased metabolism of Zileuton caused by Osimertinib mediated induction of CYP450 enzyme.	Lung cancer [2C25]	[48]
Capmatinib	DMYCXKL	Moderate	Decreased metabolism of Zileuton caused by Capmatinib mediated inhibition of CYP450 enzyme.	Lung cancer [2C25]	[49]
Selpercatinib	DMZR15V	Moderate	Decreased metabolism of Zileuton caused by Selpercatinib mediated inhibition of CYP450 enzyme.	Lung cancer [2C25]	[17]
Calaspargase pegol	DMQZBXI	Moderate	Increased risk of hepatotoxicity by the combination of Zileuton and Calaspargase pegol.	Malignant haematopoietic neoplasm [2B33]	[50]
Idelalisib	DM602WT	Moderate	Increased risk of hepatotoxicity by the combination of Zileuton and Idelalisib.	Mature B-cell leukaemia [2A82]	[51]
IPI-145	DMWA24P	Moderate	Decreased metabolism of Zileuton caused by IPI-145 mediated inhibition of CYP450 enzyme.	Mature B-cell leukaemia [2A82]	[52]
Vemurafenib	DM62UG5	Moderate	Decreased metabolism of Zileuton caused by Vemurafenib mediated inhibition of CYP450 enzyme.	Melanoma [2C30]	[53]
Dabrafenib	DMX6OE3	Moderate	Increased metabolism of Zileuton caused by Dabrafenib mediated induction of CYP450 enzyme.	Melanoma [2C30]	[17]
Exjade	DMHPRWG	Moderate	Decreased metabolism of Zileuton caused by Exjade mediated inhibition of CYP450 enzyme.	Mineral absorption/transport disorder [5C64]	[54]
Fedratinib	DM4ZBK6	Moderate	Decreased metabolism of Zileuton caused by Fedratinib mediated inhibition of CYP450 enzyme.	Myeloproliferative neoplasm [2A20]	[17]
Nilotinib	DM7HXWT	Moderate	Decreased metabolism of Zileuton caused by Nilotinib mediated inhibition of CYP450 enzyme.	Myeloproliferative neoplasm [2A20]	[55]
Olaparib	DM8QB1D	Moderate	Increased metabolism of Zileuton caused by Olaparib mediated induction of CYP450 enzyme.	Ovarian cancer [2C73]	[27]
Rucaparib	DM9PVX8	Moderate	Decreased metabolism of Zileuton caused by Rucaparib mediated inhibition of CYP450 enzyme.	Ovarian cancer [2C73]	[56]
Rasagiline	DM3WKQ4	Major	Decreased metabolism of Zileuton caused by Rasagiline mediated inhibition of CYP450 enzyme.	Parkinsonism [8A00]	[27]
Abametapir	DM2RX0I	Moderate	Decreased metabolism of Zileuton caused by Abametapir mediated inhibition of CYP450 enzyme.	Pediculosis [1G00]	[57]
Lefamulin	DME6G97	Moderate	Decreased metabolism of Zileuton caused by Lefamulin mediated inhibition of CYP450 enzyme.	Pneumonia [CA40]	[58]
Lonafarnib	DMGM2Z6	Moderate	Decreased metabolism of Zileuton caused by Lonafarnib mediated inhibition of CYP450 enzyme.	Premature ageing appearance [LD2B]	[59]
Enzalutamide	DMGL19D	Moderate	Increased metabolism of Zileuton caused by Enzalutamide mediated induction of CYP450 enzyme.	Prostate cancer [2C82]	[60]
Temsirolimus	DMS104F	Moderate	Increased plasma concentrations of Zileuton and Temsirolimus due to competitive inhibition of the same metabolic pathway.	Renal cell carcinoma [2C90]	[61]
Leflunomide	DMR8ONJ	Major	Increased risk of hepatotoxicity by the combination of Zileuton and Leflunomide.	Rheumatoid arthritis [FA20]	[38]
Asenapine	DMSQZE2	Moderate	Decreased metabolism of Zileuton caused by Asenapine mediated inhibition of CYP450 enzyme.	Schizophrenia [6A20]	[62]
Pimozide	DMW83TP	Major	Decreased metabolism of Zileuton caused by Pimozide mediated inhibition of CYP450 enzyme.	Schizophrenia [6A20]	[27]
Telotristat ethyl	DMDIYFZ	Moderate	Increased metabolism of Zileuton caused by Telotristat ethyl mediated induction of CYP450 enzyme.	Small intestine developmental anomaly [DA90]	[17]
Larotrectinib	DM26CQR	Moderate	Decreased metabolism of Zileuton caused by Larotrectinib mediated inhibition of CYP450 enzyme.	Solid tumour/cancer [2A00-2F9Z]	[27]
Trabectedin	DMG3Y89	Moderate	Increased risk of hepatotoxicity by the combination of Zileuton and Trabectedin.	Solid tumour/cancer [2A00-2F9Z]	[17]
Armodafinil	DMGB035	Minor	Increased metabolism of Zileuton caused by Armodafinil mediated induction of CYP450 enzyme.	Solid tumour/cancer [2A00-2F9Z]	[63]
LEE011	DMMX75K	Moderate	Decreased metabolism of Zileuton caused by LEE011 mediated inhibition of CYP450 enzyme.	Solid tumour/cancer [2A00-2F9Z]	[64]
Fostamatinib	DM6AUHV	Moderate	Decreased metabolism of Zileuton caused by Fostamatinib mediated inhibition of CYP450 enzyme.	Thrombocytopenia [3B64]	[65]
Sirolimus	DMGW1ID	Moderate	Increased plasma concentrations of Zileuton and Sirolimus due to competitive inhibition of the same metabolic pathway.	Transplant rejection [NE84]	[61]
Tacrolimus	DMZ7XNQ	Moderate	Increased plasma concentrations of Zileuton and Tacrolimus due to competitive inhibition of the same metabolic pathway.	Transplant rejection [NE84]	[61]
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Drug Inactive Ingredient(s) (DIG) and Formulation(s) of This Drug

DIG

DIG Name	DIG ID	PubChem CID	Functional Classification
Mannitol	E00103	6251	Diluent; Flavoring agent; Lyophilization aid; Plasticizing agent; Tonicity agent
Sodium lauryl sulfate	E00464	3423265	Emulsifying agent; Modified-release agent; Penetration agent; Solubilizing agent; Surfactant; lubricant
Crospovidone	E00626	Not Available	Disintegrant
Eisenoxyd	E00585	56841934	Colorant
Ferric hydroxide oxide yellow	E00539	23320441	Colorant
Glyceryl dibehenate	E00537	22477175	Binding agent; Coating agent; Flavoring agent; Modified-release agent; Viscosity-controlling agent; lubricant
Magnesium stearate	E00208	11177	lubricant
Polyethylene glycol 400	E00653	Not Available	Coating agent; Diluent; Ointment base; Plasticizing agent; Solvent; Suppository base; lubricant
Povidone	E00667	Not Available	Binding agent; Coating agent; Disintegrant; Film/membrane-forming agent; Solubilizing agent; Suspending agent
Propylene glycol	E00040	1030	Antimicrobial preservative; Humectant; Plasticizing agent; Solvent
Silicon dioxide	E00670	Not Available	Anticaking agent; Opacifying agent; Viscosity-controlling agent
Talc	E00520	16211421	Anticaking agent; Diluent; Glidant; lubricant
Titanium dioxide	E00322	26042	Coating agent; Colorant; Opacifying agent
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⏷ Show the Full List of 13 Pharmaceutical Excipients of This Drug

Pharmaceutical Formulation

Formulation Name	Drug Dosage	Dosage Form	Route
Zileuton 600 mg tablet	600 mg	12 HR Extended Release Oral Tablet	Oral
Zileuton 600 mg tablet	600 mg	Oral Tablet	Oral

Jump to Detail Pharmaceutical Formulation Page of This Drug

References

1	Zileuton FDA Label
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6	5-lipoxygenase inhibitor zileuton attenuates ischemic brain damage: involvement of matrix metalloproteinase 9. Neurol Res. 2009 Oct;31(8):848-52.
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9	Synthetic and natural compounds that interact with human cytochrome P450 1A2 and implications in drug development. Curr Med Chem. 2009;16(31):4066-218.
10	Prostaglandins and leukotriene B4 are potent inhibitors of 11beta-hydroxysteroid dehydrogenase type 2 activity in human choriocarcinoma JEG-3 cells. Biol Reprod. 1999 Jul;61(1):40-5.
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12	Mechanism-based inhibition of human liver microsomal cytochrome P450 1A2 by zileuton, a 5-lipoxygenase inhibitor. Drug Metab Dispos. 2003 Nov;31(11):1352-60.
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39	Product Information. Juxtapid (lomitapide). Aegerion Pharmaceuticals Inc, Cambridge, MA.
40	Product Information. Vaprisol (conivaptan). Cumberland Pharmaceuticals Inc, Nashville, TN.
41	Product Information. Givlaari (givosiran). Alnylam Pharmaceuticals, Cambridge, MA.
42	Product Information. Orladeyo (berotralstat). BioCryst Pharmaceuticals Inc, Durham, NC.
43	Product Information. Rozerem (ramelteon). Takeda Pharmaceuticals America, Lincolnshire, IL.
44	Product Information. Hetlioz (tasimelteon). Vanda Pharmaceuticals Inc, Rockville, MD.
45	Product Information. Lotronex (alosetron). Glaxo Wellcome, Research Triangle Park, NC.
46	Product Information. Alunbrig (brigatinib). Ariad Pharmaceuticals Inc, Cambridge, MA.
47	Product Information. Lorbrena (lorlatinib). Pfizer U.S. Pharmaceuticals Group, New York, NY.
48	Product Information. Tagrisso (osimertinib). Astra-Zeneca Pharmaceuticals, Wilmington, DE.
49	Product Information. Tabrecta (capmatinib). Novartis Pharmaceuticals, East Hanover, NJ.
50	Al-Nawakil C, Willems L, Mauprivez C, et.al "Successful treatment of l-asparaginase-induced severe acute hepatotoxicity using mitochondrial cofactors." Leuk Lymphoma 55 (2014): 1670-4. [PMID: 24090500]
51	Product Information. Zydelig (idelalisib). Gilead Sciences, Foster City, CA.
52	Product Information. Copiktra (duvelisib). Verastem, Inc., Needham, MA.
53	Product Information. Zelboraf (vemurafenib). Genentech, South San Francisco, CA.
54	Product Information. Exjade (deferasirox). Novartis Pharmaceuticals, East Hanover, NJ.
55	Product Information. Tasigna (nilotinib). Novartis Pharmaceuticals, East Hanover, NJ.
56	EMA. European Medicines Agency. European Union "EMA - List of medicines under additional monitoring.".
57	Product Information. Xeglyze (abametapir topical). Dr. Reddy's Laboratories Inc, Upper Saddle River, NJ.
58	Product Information. Xenleta (lefamulin). Nabriva Therapeutics US, Inc., King of Prussia, PA.
59	Product Information. Zokinvy (lonafarnib). Eiger BioPharmaceuticals, Palo Alto, CA.
60	Benoist G, van Oort I, et al "Drug-drug interaction potential in men treated with enzalutamide: Mind the gap." Br J Clin Pharmacol 0 (2017): epub. [PMID: 28881501]
61	Product Information. Prograf (tacrolimus). Fujisawa, Deerfield, IL.
62	Product Information. Saphris (asenapine). Schering-Plough Corporation, Kenilworth, NJ.
63	Doherty MM, Charman WN "The mucosa of the small intestine: how clinically relevant as an organ of drug metabolism?" Clin Pharmacokinet 41 (2002): 235-53. [PMID: 11978143]
64	DSouza DL, Levasseur LM, Nezamis J, Robbins DK, Simms L, Koch KM "Effect of alosetron on the pharmacokinetics of alprazolam." J Clin Pharmacol 41 (2001): 452-4. [PMID: 11304902]
65	Product Information. Tavalisse (fostamatinib). Rigel Pharmaceuticals, South San Francisco, CA.