Details of the Drug

General Information of Drug (ID: DMUR64T)

Drug Name

Lesinurad

Synonyms

LESINURAD; 878672-00-5; RDEA594; Zurampic; RDEA 594; UNII-09ERP08I3W; RDEA-594; 2-((5-bromo-4-(4-cyclopropylnaphthalen-1-yl)-4H-1,2,4-triazol-3-yl)thio)acetic acid; 09ERP08I3W; AK323774; C17H14BrN3O2S; 2-[[5-bromo-4-(4-cyclopropylnaphthalen-1-yl)-4H-1,2,4-triazol-3-yl]thio]acetic acid; 2-[[5-bromo-4-(4-cyclopropylnaphthalen-1-yl)-1,2,4-triazol-3-yl]sulfanyl]acetic acid; 2-(5-Bromo-4-(4-cyclopropylnaphthalen-1-yl)-4H-1,2,4-triazol-3-ylthio)acetic acid

Indication

Disease Entry	ICD 11	Status	REF
Hyperuricaemia	5C55.Y	Approved	[1], [2]

Drug Type

Small molecular drug

Structure

3D MOL

2D MOL

#Ro5 Violations (Lipinski): 0

Molecular Weight (mw)

404.3

Topological Polar Surface Area (xlogp)

4.7

Rotatable Bond Count (rotbonds)

Hydrogen Bond Donor Count (hbonddonor)

Hydrogen Bond Acceptor Count (hbondacc)

ADMET Property

BDDCS Class: Biopharmaceutics Drug Disposition Classification System (BDDCS) Class 2: low solubility and high permeability [3]
Clearance: The drug present in the plasma can be removed from the body at the rate of 1.43 mL/min/kg [4]
Half-life: The concentration or amount of drug in body reduced by one-half in 5 hours [4]
Metabolism: The drug is metabolized via the polymorphic cytochrome P450 CYP2C9 enzyme [5]
Unbound Fraction: The unbound fraction of drug in plasma is 0.02% [4]
Vd: The volume of distribution (Vd) of drug is 20 L [6]

Chemical Identifiers

Formula: C17H14BrN3O2S
IUPAC Name: 2-[[5-bromo-4-(4-cyclopropylnaphthalen-1-yl)-1,2,4-triazol-3-yl]sulfanyl]acetic acid
Canonical SMILES: C1CC1C2=CC=C(C3=CC=CC=C23)N4C(=NN=C4Br)SCC(=O)O
InChI: InChI=1S/C17H14BrN3O2S/c18-16-19-20-17(24-9-15(22)23)21(16)14-8-7-11(10-5-6-10)12-3-1-2-4-13(12)14/h1-4,7-8,10H,5-6,9H2,(H,22,23)
InChIKey: FGQFOYHRJSUHMR-UHFFFAOYSA-N

Cross-matching ID

PubChem CID: 53465279
ChEBI ID: CHEBI:90929
CAS Number: 878672-00-5
DrugBank ID: DB11560
TTD ID: D0C3SW
VARIDT ID: DR01130
INTEDE ID: DR0926
ACDINA ID: D00354

Molecular Interaction Atlas of This Drug

Drug Therapeutic Target (DTT)

DTT Name	DTT ID	UniProt ID	MOA	REF
Urate anion exchanger 1 (URAT1)	TTA592U	S22AC_HUMAN	Modulator	[7]

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Drug-Metabolizing Enzyme (DME)

DME Name	DME ID	UniProt ID	MOA	REF
Cytochrome P450 2C9 (CYP2C9)_{Main DME}	DE5IED8	CP2C9_HUMAN	Substrate	[8]

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Molecular Interaction Atlas (MIA)

MIA Detail

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Drug-Drug Interaction (DDI) Information of This Drug

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

DDI Drug Name	DDI Drug ID	Severity	Mechanism	Comorbidity	REF
Oliceridine	DM6MDCF	Moderate	Increased metabolism of Lesinurad caused by Oliceridine mediated induction of CYP450 enzyme.	Acute pain [MG31]	[21]
LY2835219	DM93VBZ	Moderate	Increased metabolism of Lesinurad caused by LY2835219 mediated induction of CYP450 enzyme.	Breast cancer [2C60-2C6Y]	[22]
Tucatinib	DMBESUA	Moderate	Increased metabolism of Lesinurad caused by Tucatinib mediated induction of CYP450 enzyme.	Breast cancer [2C60-2C6Y]	[23]
PF-04449913	DMSB068	Moderate	Increased metabolism of Lesinurad caused by PF-04449913 mediated induction of CYP450 enzyme.	Chronic myelomonocytic leukaemia [2A40]	[24]
Osilodrostat	DMIJC9X	Moderate	Increased metabolism of Lesinurad caused by Osilodrostat mediated induction of CYP450 enzyme.	Cushing syndrome [5A70]	[23]
MK-8228	DMOB58Q	Moderate	Increased metabolism of Lesinurad caused by MK-8228 mediated induction of CYP450 enzyme.	Cytomegaloviral disease [1D82]	[25]
Bay 80-6946	DMLOS5R	Moderate	Increased metabolism of Lesinurad caused by Bay 80-6946 mediated induction of CYP450 enzyme.	Follicular lymphoma [2A80]	[26]
Ripretinib	DM958QB	Moderate	Increased metabolism of Lesinurad caused by Ripretinib mediated induction of CYP450 enzyme.	Gastrointestinal stromal tumour [2B5B]	[27]
Avapritinib	DMK2GZX	Moderate	Increased metabolism of Lesinurad caused by Avapritinib mediated induction of CYP450 enzyme.	Gastrointestinal stromal tumour [2B5B]	[28]
MK-1439	DM215WE	Major	Increased metabolism of Lesinurad caused by MK-1439 mediated induction of CYP450 enzyme.	Human immunodeficiency virus disease [1C60-1C62]	[28]
Fostemsavir	DM50ILT	Minor	Increased metabolism of Lesinurad caused by Fostemsavir mediated induction of CYP450 enzyme.	Human immunodeficiency virus disease [1C60-1C62]	[23]
Pemigatinib	DM819JF	Moderate	Increased metabolism of Lesinurad caused by Pemigatinib mediated induction of CYP450 enzyme.	Liver cancer [2C12]	[29]
Brigatinib	DM7W94S	Moderate	Increased metabolism of Lesinurad caused by Brigatinib mediated induction of CYP450 enzyme.	Lung cancer [2C25]	[27]
Lurbinectedin	DMEFRTZ	Moderate	Increased metabolism of Lesinurad caused by Lurbinectedin mediated induction of CYP450 enzyme.	Lung cancer [2C25]	[30]
PF-06463922	DMKM7EW	Moderate	Increased metabolism of Lesinurad caused by PF-06463922 mediated induction of CYP450 enzyme.	Lung cancer [2C25]	[27]
Capmatinib	DMYCXKL	Moderate	Increased metabolism of Lesinurad caused by Capmatinib mediated induction of CYP450 enzyme.	Lung cancer [2C25]	[31]
Selpercatinib	DMZR15V	Moderate	Increased metabolism of Lesinurad caused by Selpercatinib mediated induction of CYP450 enzyme.	Lung cancer [2C25]	[23]
IPI-145	DMWA24P	Moderate	Increased metabolism of Lesinurad caused by IPI-145 mediated induction of CYP450 enzyme.	Mature B-cell leukaemia [2A82]	[32]
Acalabrutinib	DM7GCVW	Moderate	Increased metabolism of Lesinurad caused by Acalabrutinib mediated induction of CYP450 enzyme.	Mature B-cell lymphoma [2A85]	[33]
Ubrogepant	DM749I3	Moderate	Increased metabolism of Lesinurad caused by Ubrogepant mediated induction of CYP450 enzyme.	Migraine [8A80]	[34]
Entrectinib	DMMPTLH	Moderate	Increased metabolism of Lesinurad caused by Entrectinib mediated induction of CYP450 enzyme.	Non-small cell lung cancer [2C25]	[28]
Rucaparib	DM9PVX8	Moderate	Decreased metabolism of Lesinurad caused by Rucaparib mediated inhibition of CYP450 enzyme.	Ovarian cancer [2C73]	[25]
Macimorelin	DMQYJIR	Moderate	Increased metabolism of Lesinurad caused by Macimorelin mediated induction of CYP450 enzyme.	Pituitary gland disorder [5A60-5A61]	[35]
Lefamulin	DME6G97	Moderate	Increased metabolism of Lesinurad caused by Lefamulin mediated induction of CYP450 enzyme.	Pneumonia [CA40]	[36]
Darolutamide	DMV7YFT	Moderate	Increased metabolism of Lesinurad caused by Darolutamide mediated induction of CYP450 enzyme.	Prostate cancer [2C82]	[37]
Larotrectinib	DM26CQR	Moderate	Increased metabolism of Lesinurad caused by Larotrectinib mediated induction of CYP450 enzyme.	Solid tumour/cancer [2A00-2F9Z]	[27]
Fostamatinib	DM6AUHV	Moderate	Increased metabolism of Lesinurad caused by Fostamatinib mediated induction of CYP450 enzyme.	Thrombocytopenia [3B64]	[23]
Elagolix	DMB2C0E	Moderate	Increased metabolism of Lesinurad caused by Elagolix mediated induction of CYP450 enzyme.	Uterine fibroid [2E86]	[38]
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Drug Inactive Ingredient(s) (DIG) and Formulation(s) of This Drug

DIG

DIG Name	DIG ID	PubChem CID	Functional Classification
FD&C blue no. 1	E00263	19700	Colorant
FD&C blue no. 2	E00446	2723854	Colorant
Lactose monohydrate	E00393	104938	Binding agent; Diluent; Dry powder inhaler carrier; Lyophilization aid
Magnesium stearate	E00208	11177	lubricant
Titanium dioxide	E00322	26042	Coating agent; Colorant; Opacifying agent
Triacetin	E00080	5541	Humectant; Plasticizing agent; Solvent
Water	E00035	962	Solvent
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⏷ Show the Full List of 7 Pharmaceutical Excipients of This Drug

Pharmaceutical Formulation

Formulation Name	Drug Dosage	Dosage Form	Route
Lesinurad 200 mg tablet	200 mg	Oral Tablet	Oral

Jump to Detail Pharmaceutical Formulation Page of This Drug

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: 7673).
2	ClinicalTrials.gov (NCT01493531) Combining Lesinurad With Allopurinol in Inadequate Responders. U.S. National Institutes of Health.
3	BDDCS predictions, self-correcting aspects of BDDCS assignments, BDDCS assignment corrections, and classification for more than 175 additional drugs
4	Trend Analysis of a Database of Intravenous Pharmacokinetic Parameters in Humans for 1352 Drug Compounds
5	FDA approval: ado-trastuzumab emtansine for the treatment of patients with HER2-positive metastatic breast cancer. Clin Cancer Res. 2014 Sep 1;20(17):4436-41.
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7	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. (Target id: 1031).
8	FDA Label of Lesinurad. The 2020 official website of the U.S. Food and Drug Administration.
9	Progesterone and testosterone hydroxylation by cytochromes P450 2C19, 2C9, and 3A4 in human liver microsomes. Arch Biochem Biophys. 1997 Oct 1;346(1):161-9.
10	Tamoxifen inhibits cytochrome P450 2C9 activity in breast cancer patients. J Chemother. 2006 Aug;18(4):421-4.
11	Characterization of the oxidative metabolites of 17beta-estradiol and estrone formed by 15 selectively expressed human cytochrome p450 isoforms. Endocrinology. 2003 Aug;144(8):3382-98.
12	Summary of information on human CYP enzymes: human P450 metabolism data. Drug Metab Rev. 2002 Feb-May;34(1-2):83-448.
13	Drug-drug interactions with imatinib: an observational study. Medicine (Baltimore). 2016 Oct;95(40):e5076.
14	Drug interactions with calcium channel blockers: possible involvement of metabolite-intermediate complexation with CYP3A. Drug Metab Dispos. 2000 Feb;28(2):125-30.
15	New insights into the structural features and functional relevance of human cytochrome P450 2C9. Part I. Curr Drug Metab. 2009 Dec;10(10):1075-126.
16	A potential role for the estrogen-metabolizing cytochrome P450 enzymes in human breast carcinogenesis. Breast Cancer Res Treat. 2003 Dec;82(3):191-7.
17	A mechanistic approach to antiepileptic drug interactions. Ann Pharmacother. 1998 May;32(5):554-63.
18	Clinical pipeline report, company report or official report of Chugai Pharmaceutical (2013).
19	The pathophysiology of hyperuricaemia and its possible relationship to cardiovascular disease, morbidity and mortality. BMC Nephrol. 2013; 14: 164.
20	Urate transporter URAT1 inhibitors: a patent review (2012 - 2015).Expert Opin Ther Pat. 2016 Jul 30:1-10.
21	Bell J, Seres V, Bowron P, Lewis J, Batey R "The use of serum methadone levels in patients receiving methadone maintenance." Clin Pharmacol Ther 43 (1988): 623-9. [PMID: 3378383]
22	Product Information. Verzenio (abemaciclib). Lilly, Eli and Company, Indianapolis, IN.
23	Product Information. Diabinese (chlorpropamide). Pfizer US Pharmaceuticals, New York, NY.
24	Product Information. Daurismo (glasdegib). Pfizer U.S. Pharmaceuticals Group, New York, NY.
25	Product Information. Zurampic (lesinurad). Astra-Zeneca Pharmaceuticals, Wilmington, DE.
26	Product Information. Aliqopa (copanlisib). Bayer Pharmaceutical Inc, West Haven, CT.
27	Cerner Multum, Inc. "Australian Product Information.".
28	Cerner Multum, Inc. "UK Summary of Product Characteristics.".
29	Product Information. Pemazyre (pemigatinib). Incyte Corporation, Wilmington, DE.
30	Product Information. Zepzelca (lurbinectedin). Jazz Pharmaceuticals, Palo Alto, CA.
31	Product Information. Tabrecta (capmatinib). Novartis Pharmaceuticals, East Hanover, NJ.
32	Product Information. Copiktra (duvelisib). Verastem, Inc., Needham, MA.
33	Product Information. Calquence (acalabrutinib). Astra-Zeneca Pharmaceuticals, Wilmington, DE.
34	Product Information. Ubrelvy (ubrogepant). Allergan Inc, Irvine, CA.
35	Product Information. Macrilen (macimorelin). Aeterna Zentaris, Charleston, SC.
36	Product Information. Xenleta (lefamulin). Nabriva Therapeutics US, Inc., King of Prussia, PA.
37	Product Information. Nubeqa (darolutamide). Bayer HealthCare Pharmaceuticals Inc., Whippany, NJ.
38	Product Information. Orilissa (elagolix). AbbVie US LLC, North Chicago, IL.