PROBENECID

Details

Stereochemistry	ACHIRAL
Molecular Formula	C13H19NO4S
Molecular Weight	285.359
Optical Activity	NONE
Defined Stereocenters	0 / 0
E/Z Centers	0
Charge	0

SHOW SMILES / InChI

Structure Search

SMILES

CCCN(CCC)S(=O)(=O)C1=CC=C(C=C1)C(O)=O

InChI

InChIKey=DBABZHXKTCFAPX-UHFFFAOYSA-N

InChI=1S/C13H19NO4S/c1-3-9-14(10-4-2)19(17,18)12-7-5-11(6-8-12)13(15)16/h5-8H,3-4,9-10H2,1-2H3,(H,15,16)

HIDE SMILES / InChI

Molecular Formula	C13H19NO4S
Molecular Weight	285.359
Charge	0
Count

Stereochemistry	ACHIRAL
Additional Stereochemistry	No
Defined Stereocenters	0 / 0
E/Z Centers	0
Optical Activity	NONE

Description
Sources: https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=ae126418-5474-4fbe-b83c-bde8b2b4ae6e

Probenecid is the prototypical uricosuric agent. It inhibits the renal excretion of organic anions and reduces tubular reabsorption of urate. Probenecid has also been used to treat patients with renal impairment, and, because it reduces the renal tubular excretion of other drugs, has been used as an adjunct to antibacterial therapy. Probenecid is used for treatment of the hyperuricemia associated with gout and gouty arthritis. Probenecid is a uricosuric and renal tubular blocking agent. It inhibits the tubular reabsorption of urate, thus increasing the urinary excretion of uric acid and decreasing serum urate levels. Effective uricosuria reduces the miscible urate pool, retards urate deposition, and promotes resorption of urate deposits. Probenecid inhibits the tubular secretion of penicillin and usually increases penicillin plasma levels by any route the antibiotic is given. A 2-fold to 4-fold elevation has been demonstrated for various penicillins. Probenecid decreases both hepatic and renal excretion of sulfobromophthalein (BSP). The tubular reabsorption of phosphorus is inhibited in hypoparathyroid but not in euparathyroid individuals. Probenecid does not influence plasma concentrations of salicylates, nor the excretion of streptomycin, chloramphenicol, chlortetracycline, oxytetracycline, or neomycin.

Originator

Approval Year

Targets

Primary Target	Pharmacology	Potency
Solute carrier family 22 member 6 19 Target ID: CHEMBL1641347 Sources: https://www.ncbi.nlm.nih.gov/pubmed/11426832	Inhibitor 8297	12.1 µM [Ki]
Solute carrier family 22 member 8 17 Target ID: CHEMBL1641348 Sources: https://www.ncbi.nlm.nih.gov/pubmed/11426832	Inhibitor 8297	5.6 µM [IC50]
Solute carrier family 22 member 11 12 Target ID: CHEMBL2073677 Sources: https://www.ncbi.nlm.nih.gov/pubmed/?term=12130730	Inhibitor 8297

Conditions

Condition	Modality	Targets	Highest Phase	Product
Gout 28 Sources: https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=ae126418-5474-4fbe-b83c-bde8b2b4ae6e	Palliative		Approved 8429	PROBENECID Approved Use For treatment of the hyperuricemia associated with gout and gouty arthritis. As an adjuvant to therapy with penicillin or with ampicillin, methicillin, oxacillin, cloxacillin, or nafcillin, for elevation and prolongation of plasma levels by whatever route the antibiotic is given. Launch Date 1983
Gouty arthritis 4 Sources: https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=ae126418-5474-4fbe-b83c-bde8b2b4ae6e	Palliative		Approved 8429	PROBENECID Approved Use For treatment of the hyperuricemia associated with gout and gouty arthritis. As an adjuvant to therapy with penicillin or with ampicillin, methicillin, oxacillin, cloxacillin, or nafcillin, for elevation and prolongation of plasma levels by whatever route the antibiotic is given. Launch Date 1983

C_max

Value	Dose	Analyte	Population
148.6 μg/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/7175716/	2000 mg single, oral dose: 2000 mg route of administration: Oral experiment type: SINGLE co-administered:	PROBENECID plasma	Homo sapiens population: HEALTHY age: ADULT sex: MALE food status: FASTED
35.3 μg/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/7175716/	500 mg single, oral dose: 500 mg route of administration: Oral experiment type: SINGLE co-administered:	PROBENECID plasma	Homo sapiens population: HEALTHY age: ADULT sex: MALE food status: FASTED
69.6 μg/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/7175716/	1000 mg single, oral dose: 1000 mg route of administration: Oral experiment type: SINGLE co-administered:	PROBENECID plasma	Homo sapiens population: HEALTHY age: ADULT sex: MALE food status: FASTED

AUC

Value	Dose	Analyte	Population
2109 μg × h/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/7175716/	2000 mg single, oral dose: 2000 mg route of administration: Oral experiment type: SINGLE co-administered:	PROBENECID plasma	Homo sapiens population: HEALTHY age: ADULT sex: MALE food status: FASTED
292 μg × h/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/7175716/	500 mg single, oral dose: 500 mg route of administration: Oral experiment type: SINGLE co-administered:	PROBENECID plasma	Homo sapiens population: HEALTHY age: ADULT sex: MALE food status: FASTED
772 μg × h/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/7175716/	1000 mg single, oral dose: 1000 mg route of administration: Oral experiment type: SINGLE co-administered:	PROBENECID plasma	Homo sapiens population: HEALTHY age: ADULT sex: MALE food status: FASTED

T_1/2

Value	Dose	Analyte	Population
8.5 h EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/7175716/	2000 mg single, oral dose: 2000 mg route of administration: Oral experiment type: SINGLE co-administered:	PROBENECID plasma	Homo sapiens population: HEALTHY age: ADULT sex: MALE food status: FASTED
4.2 h EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/7175716/	500 mg single, oral dose: 500 mg route of administration: Oral experiment type: SINGLE co-administered:	PROBENECID plasma	Homo sapiens population: HEALTHY age: ADULT sex: MALE food status: FASTED
4.9 h EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/7175716/	1000 mg single, oral dose: 1000 mg route of administration: Oral experiment type: SINGLE co-administered:	PROBENECID plasma	Homo sapiens population: HEALTHY age: ADULT sex: MALE food status: FASTED

Overview

CYP3A4	CYP2C9	CYP2D6	hERG
inducer 781	inhibitor 1767

OverviewOther

Other Inhibitor	Other Substrate	Other Inducer
CYP2C19 1478 MRP4 204 UGT 35 MRP1 106 OAT4 146 MRP5 22 OAT2 145 OAT3 642 OAT1 599		CYP2C8 168

Drug as perpetrator

Target	Modality	Activity	Clinical evidence
MRP1 172	inhibitor 3277 Sources: https://bioinformatics.charite.de/transformer/index.php?site=fullinfo&cname=000057669	weak
MRP4 238	inhibitor 3277 Sources: http://transportal.compbio.ucsf.edu/compounds/probenecid/	yes [IC50 100 uM]	yes (co-administration study) Comment: MRP4-expressing V79 vesicles (cholyltaurine); Coadministration of Probenecid (1000 mg QD oral) increased Cefmetazole (5 mg/kg QD IV-infusion (1-hr)) AUC by 1.6-fold. Sources: http://transportal.compbio.ucsf.edu/compounds/probenecid/
OAT3 644	inhibitor 3277 Sources: http://transportal.compbio.ucsf.edu/compounds/probenecid/	yes [IC50 3.1 uM]	yes (co-administration study) Comment: CHO-OAT3 (cimetidine); Coadministration of Probenecid (1000 mg QD oral) increased Dicloxacillin (500 mg SD oral) AUC by 1.9-fold and Cmax by 1.8-fold. Sources: http://transportal.compbio.ucsf.edu/compounds/probenecid/
OAT1 603	inhibitor 3277 Sources: http://transportal.compbio.ucsf.edu/compounds/probenecid/	yes [IC50 3.9 uM]	yes (co-administration study) Comment: CHO-OAT1 (cidofovir); Coadministration of Probenecid (1000 mg QD oral) increased Dicloxacillin (500 mg SD oral) AUC by 1.9-fold and Cmax by 1.8-fold. Sources: http://transportal.compbio.ucsf.edu/compounds/probenecid/
MRP5 48	inhibitor 3277 Sources: http://transportal.compbio.ucsf.edu/compounds/probenecid/	yes [IC50 34 uM]	yes (co-administration study) Comment: MRP5-expressing HEK293 vesicles (carboxydichlorofluorescein); Coadministration of Probenecid (1000 mg QD oral) increased Cefmetazole (2000 mg QD IV-infusion (5 min)) AUC by 1.6-fold. Sources: http://transportal.compbio.ucsf.edu/compounds/probenecid/
OAT4 146	inhibitor 3277 Sources: https://bioinformatics.charite.de/transformer/index.php?site=fullinfo&cname=000057669	yes [Ki 54.9 uM]
OAT2 147	inhibitor 3277 Sources: http://transportal.compbio.ucsf.edu/compounds/probenecid/	yes [Ki 766 uM]	yes (co-administration study) Comment: S2-OAT2 (prostaglandin F2alpha); Coadministration of Probenecid (1000 mg QD oral) increased Dicloxacillin (500 mg SD oral) AUC by 1.9-fold and Cmax by 1.8-fold. Sources: http://transportal.compbio.ucsf.edu/compounds/probenecid/
CYP2C19 1553	inhibitor 3277 Sources: https://bioinformatics.charite.de/transformer/index.php?site=fullinfo&cname=000057669	yes	yes (co-administration study) Comment: Coadministration of Probenecid (1000 mg qid on Day 1, 500 mg qid on Days 2-3, and 500 mg QD on Day 4) increased Naproxen (500 mg QD on Day 4) AUCinf by over 2-fold. Sources: https://bioinformatics.charite.de/transformer/index.php?site=fullinfo&cname=000057669
CYP2C8 965	inducer 1573 Sources: https://bioinformatics.charite.de/transformer/index.php?site=fullinfo&cname=000057669	yes	yes (co-administration study) Comment: Coadministration of Probenecid (500 mg BID X 10 days) decreased Carbamazepine (200 mg QD on Day 6) AUCinf by 18% and increased Cmax by 3% while increased Carbamazepine 10,11-epoxide AUCinf by 35% and Cmax by 47%. Sources: https://bioinformatics.charite.de/transformer/index.php?site=fullinfo&cname=000057669
CYP2C9 1819	inhibitor 3277 Sources: https://bioinformatics.charite.de/transformer/index.php?site=fullinfo&cname=000057669	yes	yes (co-administration study) Comment: Coadministration of Probenecid (1000 mg qid on Day 1, 500 mg qid on Days 2-3, and 500 mg QD on Day 4) increased Naproxen (500 mg QD on Day 4) AUCinf by over 2-fold. Sources: https://bioinformatics.charite.de/transformer/index.php?site=fullinfo&cname=000057669
CYP3A4 1925	inducer 1573 Sources: https://bioinformatics.charite.de/transformer/index.php?site=fullinfo&cname=000057669	yes	yes (co-administration study) Comment: Coadministration of Probenecid (500 mg BID X 10 days) decreased Carbamazepine (200 mg QD on Day 6) AUCinf by 18% and increased Cmax by 3% while increased Carbamazepine 10,11-epoxide AUCinf by 35% and Cmax by 47%. Sources: https://bioinformatics.charite.de/transformer/index.php?site=fullinfo&cname=000057669
UGT 59	inhibitor 3277 Sources: https://pubmed.ncbi.nlm.nih.gov/2570186/	yes	yes (co-administration study) Comment: Coadministration of Probenecid (500 mg q8h X 3 days) increased Zidovudine (q8h x 3 day) AUC by 80%. Sources: https://pubmed.ncbi.nlm.nih.gov/2570186/

Sourcing

Vendor/Aggregator	ID	URL
ChEBI	CHEBI:8426	https://www.ebi.ac.uk/chebi/searchId.do?chebiId=CHEBI:8426
ChemicalBook	CB9134579	https://www.chemicalbook.com/ChemicalProductProperty_EN_CB9134579
MolPort	MolPort-000-145-935	https://www.molport.com/shop/molecule-link/MolPort-000-145-935
Selleck Chemicals	probenecid-benemid	http://www.selleckchem.com/products/probenecid-benemid.html
ZINC	ZINC000000001982	http://zinc15.docking.org/substances/ZINC000000001982
eMolecules	27523493	https://www.emolecules.com/cgi-bin/more?vid=27523493
eMolecules	593868	https://www.emolecules.com/cgi-bin/more?vid=593868

PubMed

Title	Date	PubMed
Nephrotic syndrome caused by probenecid.	1967 Jan 2	6071127
Probenecid, nephrotic syndrome, and renal failure.	1968 May	5655316
Penicillin-induced haemolytic anaemia.	1968 Sep 7	5668001
Probenecid and renal failure.	1968 Sep 7	5667986
Haematuria during methicillin therapy.	1971 Jul	5560145
Probenecid-induced nephrotic syndrome.	1972 Sep	5051645
Acute Heinz-body anaemia in burned patients.	1973 Sep 1	4124995
Letter: Drug-induced red cell aplasia.	1974 Oct 19	4471350
Skin sensitizing properties of arylalcanoic acids and their analogues.	1979 Sep	509935
Treatment of gonorrhea: comparison of cefotaxime and penicillin.	1981 May	6271049
Effect of probenecid on the natriuresis and renin release induced by bumetanide in man.	1981 Nov-Dec	7040495
One gram of cefoxitin cures uncomplicated gonococcal urethritis caused by penicillinase-producing Neisseria gonorrhoeae (PPNG).	1983 Jul-Sep	6228024
Enhancement of cisplatin nephrotoxicity by probenecid.	1984 Feb	6538115
Immune hemolytic anemia associated with probenecid.	1985 Sep	4036870
Probenecid induced immune hemolytic anemia.	1986 Feb	3701734
Mechanism of S-(1,2-dichlorovinyl)glutathione-induced nephrotoxicity.	1986 Jan 15	2867768
The mechanisms of target cell injury by nephrotoxins.	1986 Jun-Jul	3781430
In vivo nephrotoxic action of an isomeric mixture of S-(1-phenyl-2-hydroxyethyl)glutathione and S-(2-phenyl-2-hydroxyethyl)glutathione in Fischer-344 rats.	1991 Mar 25	1673268
Molecular cloning and characterization of multispecific organic anion transporter 4 expressed in the placenta.	2000 Feb 11	10660625
Subjective sensation of heaviness in gout patients.	2000 Jun	10920575
Urate transport via human PAH transporter hOAT1 and its gene structure.	2003 Jan	12472777
ATP binding cassette multidrug transporters limit the anti-HIV activity of zidovudine and indinavir in infected human macrophages.	2004 Aug	15456083
Role of two adjacent cytoplasmic tyrosine residues in MRP1 (ABCC1) transport activity and sensitivity to sulfonylureas.	2005 Feb 1	15652236
The outcome of oropharyngeal gonorrhoea treatment with different regimens.	2005 Jan	15705277
Prediction of genotoxicity of chemical compounds by statistical learning methods.	2005 Jun	15962942
Functional characterization of rat organic anion transporter 5 (Slc22a19) at the apical membrane of renal proximal tubules.	2005 Nov	16079298
MRP2 (ABCC2) transports taxanes and confers paclitaxel resistance and both processes are stimulated by probenecid.	2005 Sep 20	15849751
One center's experience: the serology and drugs associated with drug-induced immune hemolytic anemia--a new paradigm.	2007 Apr	17381629
Membrane Based Measurement Technology for in situ Monitoring of Gases in Soil.	2009	22399937
Pharmacological characterization of pannexin-1 currents expressed in mammalian cells.	2009 Feb	19023039
Efficacy and tolerability of urate-lowering drugs in gout: a randomised controlled trial of benzbromarone versus probenecid after failure of allopurinol.	2009 Jan	18250112
Prognostic significance of p53-expression in colorectal carcinoma as measured by a luminometric immunoassay.	2010 Oct 8	21063465
Interactions of human organic anion transporter 1 (hOAT1) with substances associated with forensic toxicology.	2011 Jul	21561794
Uricosuric and nephroprotective properties of Ramulus Mori ethanol extract in hyperuricemic mice.	2012 Oct 11	22967667
Targeting organic anion transporter 3 with probenecid as a novel anti-influenza a virus strategy.	2013 Jan	23129053
Interactions with selected drug renal transporters and transporter-mediated cytotoxicity in antiviral agents from the group of acyclic nucleoside phosphonates.	2013 Sep 15	23856525
A correlation between the in vitro drug toxicity of drugs to cell lines that express human P450s and their propensity to cause liver injury in humans.	2014 Jan	24085192
Gene expression regulation of Bcl2, Bax and cytochrome-C by geraniol on chronic MPTP/probenecid induced C57BL/6 mice model of Parkinson's disease.	2014 Jun 25	24768735
Neuroprotective effect of the chemical chaperone, trehalose in a chronic MPTP-induced Parkinson's disease mouse model.	2014 Sep	25064079
Novel para-phenyl substituted diindolylmethanes protect against MPTP neurotoxicity and suppress glial activation in a mouse model of Parkinson's disease.	2015 Feb	25406165

Patents

Sample Use Guides

In Vivo Use Guide

Gout: The recommended adult dosage is 250 mg (1/2 tablet) twice a day for one week, followed by 500 mg (1 tablet) twice a day thereafter.

Route of Administration: Oral

In Vitro Use Guide

Probenecid, at concentrations that had no effect on parasite viability alone (50 uM), was shown to increase the sensitivity of a highly resistant parasite isolate to the antifolates pyrimethamine, sulfadoxine, chlorcycloguanil, and dapsone by seven-, five-, three-, and threefold, respectively. Probenecid decreased the level of uptake of radiolabeled folic acid, suggesting a transport-based mechanism linked to folate salvage.

Substance Class	Chemical Created by `admin` on `Fri Dec 15 15:21:18 GMT 2023` Edited by `admin` on `Fri Dec 15 15:21:18 GMT 2023`
Record UNII	PO572Z7917
Record Status	`Validated (UNII)`
Record Version

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Name

Type

Language

PROBENECID

Official Name

English

PROBENECID [USP-RS]

Common Name

English

PROBAMPACIN COMPONENT PROBENECID

Common Name

English

PROBENECID [ORANGE BOOK]

Common Name

English

PROBENECID [MART.]

Common Name

English

PROBENECID [USP IMPURITY]

Common Name

English

PROBENECID [EP MONOGRAPH]

Common Name

English

PROBENECID [USP MONOGRAPH]

Common Name

English

PROBENATE

Common Name

English

BENZOIC ACID, 4-((DIPROPYLAMINO)SULFONYL)-

Common Name

English

PROBENECID [JAN]

Common Name

English

PROBENECID COMPONENT OF COLBENEMID

Common Name

English

probenecid [INN]

Common Name

English

PROBENECID COMPONENT OF PROBAMPACIN

Common Name

English

PROBENECID COMPONENT OF COL-PROBENECID

Common Name

English

P-(DIPROPYLSULFAMOYL)BENZOIC ACID

Common Name

English

PROBENECID [MI]

Common Name

English

BENEMID

Brand Name

English

PROBENECID [HSDB]

Common Name

English

PROBENECID COMPONENT OF PROBEN-C

Common Name

English

NSC-18786

Code

English

PROBENECID [WHO-IP]

Common Name

English

Probenecid [WHO-DD]

Common Name

English

PROBENECIDUM [WHO-IP LATIN]

Common Name

English

PROBENECID [EP IMPURITY]

Common Name

English

PROBEN-C COMPONENT PROBENECID

Common Name

English

COL-PROBENECID COMPONENT PROBENECID

Common Name

English

COLBENEMID COMPONENT PROBENECID

Common Name

English

PROBALAN

Brand Name

English

Classification Tree Code System Code

NCI_THESAURUS

C921