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Identification
NameProbenecid
Accession NumberDB01032  (APRD00167)
Typesmall molecule
Groupsapproved
Description

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. [PubChem]

Structure
Thumb
SynonymsNot Available
SaltsNot Available
Brand names
NameCompany
BenecidNot Available
BenemidNot Available
BenurylNot Available
ProbalanNot Available
ProbecidNot Available
ProbenNot Available
Brand mixtures
Brand NameIngredients
ColBenemidColchicine + Probenecid
Categories
CAS number57-66-9
WeightAverage: 285.359
Monoisotopic: 285.103478791
Chemical FormulaC13H19NO4S
InChI KeyInChIKey=DBABZHXKTCFAPX-UHFFFAOYSA-N
InChI
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)
IUPAC Name
4-(dipropylsulfamoyl)benzoic acid
SMILES
CCCN(CCC)S(=O)(=O)C1=CC=C(C=C1)C(O)=O
Mass Specshow(8.48 KB)
Taxonomy
KingdomOrganic Compounds
SuperclassBenzenoids
ClassBenzene and Substituted Derivatives
SubclassBenzenesulfonamides
Direct parentBenzenesulfonamides
Alternative parentsBenzoic Acids; Benzoyl Derivatives; Sulfonyls; Sulfonamides; Carboxylic Acids; Polyamines; Enolates
Substituentsbenzoyl; sulfonic acid derivative; sulfonamide; sulfonyl; enolate; carboxylic acid derivative; polyamine; carboxylic acid; amine; organonitrogen compound
Classification descriptionThis compound belongs to the benzenesulfonamides. These are organic compounds containing a sulfonamide group that is S-linked to a benzene ring.
Pharmacology
IndicationFor the reduction of serum uric acid concentrations in chronic gouty arthritis and tophaceous gout in patients with frequent disabling gout attacks. Has also been effectively used to promote uric acid excretion in hyperuricemia secondary to the administration of thiazide and related diuretics.
PharmacodynamicsProbenecid is a uricosuric and renal tubular blocking agent and is used in combination with colchicine to treat chronic gouty arthritis when complicated by frequent, recurrent acute attacks of gout. It inhibits the reabsorption of urate at the proximal convoluted tubule, 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. At the proximal and distal tubles, probenecid competitively inhibits the secretion of many weak organic acids including penicillins, most cephalosporins, and some other β-lactam antibiotics. This results in an increase in the plasma concentrations of acidic drugs eliminated principally by renal secretion, but only a slight increase if the drug is eliminated mainly by filtration. Thus, the drug can be used for therapeutic advantages to increase concentrations of certain β-lactam antibiotics in the treatment of gonorrhea, neurosyphilis, or pelvic inflammatory disease (PID).
Mechanism of actionProbenecid inhibits the tubular reabsorption of urate, thus increasing the urinary excretion of uric acid and decreasing serum urate levels. Probenecid may also reduce plasma binding of urate and inhibit renal secretion of uric acid at subtherapeutic concentrations. The mechanism by which probenecid inhibits renal tubular transport is not known, but the drug may inhibit transport enzymes that require a source of high energy phosphate bonds and/or nonspecifically interfere with substrate access to protein receptor sites on the kidney tubules.
AbsorptionNot Available
Volume of distributionNot Available
Protein binding75-95%
Metabolism
Route of eliminationExcreted principally in the urine as monoacyl glucuronide and unchanged drug. Alkalinization of urine increases renal probenecid excretion.
Half life6-12 hours
ClearanceNot Available
ToxicityNot Available
Affected organisms
  • Humans and other mammals
PathwaysNot Available
SNP Mediated EffectsNot Available
SNP Mediated Adverse Drug ReactionsNot Available
ADMET
Predicted ADMET features
Property Value Probability
Human Intestinal Absorption + 0.9972
Blood Brain Barrier + 0.5486
Caco-2 permeable - 0.6074
P-glycoprotein substrate Non-substrate 0.626
P-glycoprotein inhibitor I Non-inhibitor 0.8323
P-glycoprotein inhibitor II Non-inhibitor 0.9121
Renal organic cation transporter Non-inhibitor 0.8253
CYP450 2C9 substrate Non-substrate 0.7012
CYP450 2D6 substrate Non-substrate 0.9116
CYP450 3A4 substrate Non-substrate 0.6485
CYP450 1A2 substrate Non-inhibitor 0.9045
CYP450 2C9 substrate Non-inhibitor 0.9071
CYP450 2D6 substrate Non-inhibitor 0.9231
CYP450 2C19 substrate Non-inhibitor 0.9025
CYP450 3A4 substrate Non-inhibitor 0.8962
CYP450 inhibitory promiscuity Low CYP Inhibitory Promiscuity 0.9318
Ames test Non AMES toxic 0.9133
Carcinogenicity Non-carcinogens 0.6999
Biodegradation Not ready biodegradable 0.863
Rat acute toxicity 2.2821 LD50, mol/kg Not applicable
hERG inhibition (predictor I) Weak inhibitor 0.8521
hERG inhibition (predictor II) Non-inhibitor 0.7885
Pharmacoeconomics
Manufacturers
  • Merck and co inc
  • Lannett co inc
  • Ivax pharmaceuticals inc sub teva pharmaceuticals usa
  • Lederle laboratories div american cyanamid co
  • Mylan pharmaceuticals inc
  • Watson laboratories inc
Packagers
Dosage forms
FormRouteStrength
TabletOral500 mg
Prices
Unit descriptionCostUnit
Probenecid 500 mg tablet1.37USDtablet
Colchicine-Probenecid 0.5-500 mg tablet0.87USDtablet
Benuryl 500 mg Tablet0.21USDtablet
DrugBank does not sell nor buy drugs. Pricing information is supplied for informational purposes only.
PatentsNot Available
Properties
Statesolid
Experimental Properties
PropertyValueSource
melting point195 °CPhysProp
water solubility27.1 mg/LNot Available
logP3.21HANSCH,C ET AL. (1995)
pKa3.4SANGSTER (1994)
Predicted Properties
PropertyValueSource
water solubility4.25e-01 g/lALOGPS
logP1.52ALOGPS
logP2.44ChemAxon
logS-2.8ALOGPS
pKa (strongest acidic)3.53ChemAxon
physiological charge-1ChemAxon
hydrogen acceptor count4ChemAxon
hydrogen donor count1ChemAxon
polar surface area74.68ChemAxon
rotatable bond count6ChemAxon
refractivity73.81ChemAxon
polarizability29.96ChemAxon
number of rings1ChemAxon
bioavailability1ChemAxon
rule of fiveYesChemAxon
Ghose filterYesChemAxon
Veber's ruleNoChemAxon
MDDR-like ruleNoChemAxon
Spectra
SpectraNot Available
References
Synthesis ReferenceNot Available
General Reference
  1. Butler D: Wartime tactic doubles power of scarce bird-flu drug. Nature. 2005 Nov 3;438(7064):6. Pubmed
External Links
ResourceLink
KEGG DrugD00475
KEGG CompoundC07372
PubChem Compound4911
PubChem Substance46506554
ChemSpider4742
Therapeutic Targets DatabaseDAP001292
PharmGKBPA451106
IUPHAR4357
Guide to Pharmacology4357
Drug Product Database294926
RxListhttp://www.rxlist.com/cgi/generic/colbenemid.htm
Drugs.comhttp://www.drugs.com/cdi/probenecid.html
WikipediaProbenecid
ATC CodesM04AB01
AHFS Codes
  • 40:40.00
PDB EntriesNot Available
FDA labelNot Available
MSDSshow(36.9 KB)
Interactions
Drug Interactions
Drug
Acetylsalicylic acidAcetylsalicylic acid decreases the uricosuric effect of probenecid.
Bismuth SubsalicylateThe salicylate, bismuth subsalicylate, decreases the uricosuric effect of probenecid.
CefaclorProbenecid may increase the serum level of cefaclor.
CefadroxilProbenecid may increase the serum level of cefadroxil.
CefamandoleProbenecid may increase the serum level of cefamandole.
CefazolinProbenecid may increase the serum level of cefazolin.
CefepimeProbenecid may increase the serum level of cefepime.
CefiximeProbenecid may increase the serum level of cefixime.
CefmetazoleProbenecid may increase the serum level of cefmatzole.
CefonicidProbenecid may increase the serum level of cefonicib.
CefotaximeProbenecid may increase the serum level of cefotaxime.
CefotetanProbenecid may increase the serum level of cefotetan.
CefoxitinProbenecid may increase the serum level of cefoxitin.
CefprozilProbenecid may increase the serum level of cefprozil.
CefradineProbenecid may increase the serum level of cefradine.
CeftizoximeProbenecid may increase the serum level of ceftizoxime.
CefuroximeProbenecid may increase the serum level of cefuroxime.
CephalexinProbenecid may increase the serum level of cephalexin.
CephaloglycinProbenecid may increase the serum level of cephaloglycin.
Cephalothin GroupProbenecid may increase the serum level of cephalothin.
DiflunisalProbenecid increases toxicity of diflunisal
GanciclovirProbenecid increases the effect and toxicity of ganciclovir/valganciclovir
Glycerol PhenylbutyrateProbenecid may inhibit the renal excretion of metabolites of glycerol phenylbutyrate including PAGN and PAA.
IndomethacinProbenecid increases the effect/toxicity of indomethacin
KetorolacProbenecid increases toxicity of ketorolac
LoracarbefProbenecid may increase the serum level of loracarbef.
Magnesium salicylateThe salicylate, magnesium salicylate, decreases the uricosuric effect of probenecid.
MethotrexateProbenecid increases the effect and toxicity of methotrexate
Moxalactam DerivativeProbenecid may increase the serum level of the moxalactam derivative.
PralatrexateDecreases renal clearance of pralatrexate thus increasing exposure. Monitor for adverse effects.
Salicylate-sodiumThe salicylate, salicylate-sodium, decreases the uricosuric effect of probenecid.
SalsalateThe salicylate, salsalate, decreases the uricosuric effect of probenecid.
SilodosinStrong UGT2B7 inhibitors may increase levels of silodosin. Monitor concomitant therapy closely.
TapentadolIncreases the AUC of tapentadol by 57%. These changes are not considered clinically relevant and no change in dose is required.
Trisalicylate-cholineThe salicylate, trisalicylate-choline, decreases the uricosuric effect of probenecid.
ValganciclovirProbenecid may decrease excretion of Valganciclovir. Monitor for increased serum concentration and toxicity of Valganciclovir.
ZidovudineRash, malaise, myalgia
Food Interactions
  • Increase liquid intake, avoid alcohol.
  • Take with food to reduce irritation.

1. Solute carrier family 22 member 6

Kind: protein

Organism: Human

Pharmacological action: yes

Actions: inhibitor

Components

Name UniProt ID Details
Solute carrier family 22 member 6 Q4U2R8 Details

References:

  1. Takeda M, Narikawa S, Hosoyamada M, Cha SH, Sekine T, Endou H: Characterization of organic anion transport inhibitors using cells stably expressing human organic anion transporters. Eur J Pharmacol. 2001 May 11;419(2-3):113-20. Pubmed
  2. Jung KY, Takeda M, Kim DK, Tojo A, Narikawa S, Yoo BS, Hosoyamada M, Cha SH, Sekine T, Endou H: Characterization of ochratoxin A transport by human organic anion transporters. Life Sci. 2001 Sep 21;69(18):2123-35. Pubmed
  3. Takeda M, Khamdang S, Narikawa S, Kimura H, Hosoyamada M, Cha SH, Sekine T, Endou H: Characterization of methotrexate transport and its drug interactions with human organic anion transporters. J Pharmacol Exp Ther. 2002 Aug;302(2):666-71. Pubmed
  4. Hashimoto T, Narikawa S, Huang XL, Minematsu T, Usui T, Kamimura H, Endou H: Characterization of the renal tubular transport of zonampanel, a novel alpha-amino-3-hydroxy-5-methylisoxazole-4-propionic acid receptor antagonist, by human organic anion transporters. Drug Metab Dispos. 2004 Oct;32(10):1096-102. Pubmed
  5. Chen X, Ji ZL, Chen YZ: TTD: Therapeutic Target Database. Nucleic Acids Res. 2002 Jan 1;30(1):412-5. Pubmed

2. Solute carrier family 22 member 11

Kind: protein

Organism: Human

Pharmacological action: yes

Actions: inhibitor

Components

Name UniProt ID Details
Solute carrier family 22 member 11 Q9NSA0 Details

References:

  1. Enomoto A, Takeda M, Shimoda M, Narikawa S, Kobayashi Y, Kobayashi Y, Yamamoto T, Sekine T, Cha SH, Niwa T, Endou H: Interaction of human organic anion transporters 2 and 4 with organic anion transport inhibitors. J Pharmacol Exp Ther. 2002 Jun;301(3):797-802. Pubmed
  2. Babu E, Takeda M, Narikawa S, Kobayashi Y, Enomoto A, Tojo A, Cha SH, Sekine T, Sakthisekaran D, Endou H: Role of human organic anion transporter 4 in the transport of ochratoxin A. Biochim Biophys Acta. 2002 Jun 12;1590(1-3):64-75. Pubmed
  3. Takeda M, Khamdang S, Narikawa S, Kimura H, Hosoyamada M, Cha SH, Sekine T, Endou H: Characterization of methotrexate transport and its drug interactions with human organic anion transporters. J Pharmacol Exp Ther. 2002 Aug;302(2):666-71. Pubmed
  4. Hashimoto T, Narikawa S, Huang XL, Minematsu T, Usui T, Kamimura H, Endou H: Characterization of the renal tubular transport of zonampanel, a novel alpha-amino-3-hydroxy-5-methylisoxazole-4-propionic acid receptor antagonist, by human organic anion transporters. Drug Metab Dispos. 2004 Oct;32(10):1096-102. Pubmed

3. Solute carrier family 22 member 8

Kind: protein

Organism: Human

Pharmacological action: yes

Actions: inhibitor

Components

Name UniProt ID Details
Solute carrier family 22 member 8 Q8TCC7 Details

References:

  1. Kusuhara H, Sekine T, Utsunomiya-Tate N, Tsuda M, Kojima R, Cha SH, Sugiyama Y, Kanai Y, Endou H: Molecular cloning and characterization of a new multispecific organic anion transporter from rat brain. J Biol Chem. 1999 May 7;274(19):13675-80. Pubmed
  2. Takeda M, Narikawa S, Hosoyamada M, Cha SH, Sekine T, Endou H: Characterization of organic anion transport inhibitors using cells stably expressing human organic anion transporters. Eur J Pharmacol. 2001 May 11;419(2-3):113-20. Pubmed
  3. Jung KY, Takeda M, Kim DK, Tojo A, Narikawa S, Yoo BS, Hosoyamada M, Cha SH, Sekine T, Endou H: Characterization of ochratoxin A transport by human organic anion transporters. Life Sci. 2001 Sep 21;69(18):2123-35. Pubmed
  4. Takeda M, Khamdang S, Narikawa S, Kimura H, Hosoyamada M, Cha SH, Sekine T, Endou H: Characterization of methotrexate transport and its drug interactions with human organic anion transporters. J Pharmacol Exp Ther. 2002 Aug;302(2):666-71. Pubmed
  5. Sweet DH, Chan LM, Walden R, Yang XP, Miller DS, Pritchard JB: Organic anion transporter 3 (Slc22a8) is a dicarboxylate exchanger indirectly coupled to the Na+ gradient. Am J Physiol Renal Physiol. 2003 Apr;284(4):F763-9. Epub 2002 Dec 17. Pubmed
  6. Berman HM, Westbrook J, Feng Z, Gilliland G, Bhat TN, Weissig H, Shindyalov IN, Bourne PE: The Protein Data Bank. Nucleic Acids Res. 2000 Jan 1;28(1):235-42. Pubmed

4. Pannexin-1

Kind: protein

Organism: Human

Pharmacological action: unknown

Actions: antagonist

Components

Name UniProt ID Details
Pannexin-1 Q96RD7 Details

References:

  1. Silverman W, Locovei S, Dahl G: Probenecid, a gout remedy, inhibits pannexin 1 channels. Am J Physiol Cell Physiol. 2008 Sep;295(3):C761-7. Epub 2008 Jul 2. Pubmed
  2. Ransford GA, Fregien N, Qiu F, Dahl G, Conner GE, Salathe M: Pannexin 1 contributes to ATP release in airway epithelia. Am J Respir Cell Mol Biol. 2009 Nov;41(5):525-34. Epub 2009 Feb 12. Pubmed
  3. Ma W, Hui H, Pelegrin P, Surprenant A: Pharmacological characterization of pannexin-1 currents expressed in mammalian cells. J Pharmacol Exp Ther. 2009 Feb;328(2):409-18. Epub 2008 Nov 20. Pubmed
  4. Silverman WR, de Rivero Vaccari JP, Locovei S, Qiu F, Carlsson SK, Scemes E, Keane RW, Dahl G: The pannexin 1 channel activates the inflammasome in neurons and astrocytes. J Biol Chem. 2009 Jul 3;284(27):18143-51. Epub 2009 May 5. Pubmed
  5. Bunse S, Locovei S, Schmidt M, Qiu F, Zoidl G, Dahl G, Dermietzel R: The potassium channel subunit Kvbeta3 interacts with pannexin 1 and attenuates its sensitivity to changes in redox potentials. FEBS J. 2009 Nov;276(21):6258-70. Epub 2009 Sep 24. Pubmed

1. Cytochrome P450 2C9

Kind: protein

Organism: Human

Pharmacological action: unknown

Actions: inhibitor

Components

Name UniProt ID Details
Cytochrome P450 2C9 P11712 Details

References:

  1. Flockhart DA. Drug Interactions: Cytochrome P450 Drug Interaction Table. Indiana University School of Medicine (2007). Accessed May 28, 2010.
  2. Preissner S, Kroll K, Dunkel M, Senger C, Goldsobel G, Kuzman D, Guenther S, Winnenburg R, Schroeder M, Preissner R: SuperCYP: a comprehensive database on Cytochrome P450 enzymes including a tool for analysis of CYP-drug interactions. Nucleic Acids Res. 2010 Jan;38(Database issue):D237-43. Epub 2009 Nov 24. Pubmed

2. Cytochrome P450 2C19

Kind: protein

Organism: Human

Pharmacological action: unknown

Actions: inhibitor

Components

Name UniProt ID Details
Cytochrome P450 2C19 P33261 Details

References:

  1. Flockhart DA. Drug Interactions: Cytochrome P450 Drug Interaction Table. Indiana University School of Medicine (2007). Accessed May 28, 2010.
  2. Preissner S, Kroll K, Dunkel M, Senger C, Goldsobel G, Kuzman D, Guenther S, Winnenburg R, Schroeder M, Preissner R: SuperCYP: a comprehensive database on Cytochrome P450 enzymes including a tool for analysis of CYP-drug interactions. Nucleic Acids Res. 2010 Jan;38(Database issue):D237-43. Epub 2009 Nov 24. Pubmed

3. Cytochrome P450 2C8

Kind: protein

Organism: Human

Pharmacological action: unknown

Actions: inducer

Components

Name UniProt ID Details
Cytochrome P450 2C8 P10632 Details

References:

  1. Preissner S, Kroll K, Dunkel M, Senger C, Goldsobel G, Kuzman D, Guenther S, Winnenburg R, Schroeder M, Preissner R: SuperCYP: a comprehensive database on Cytochrome P450 enzymes including a tool for analysis of CYP-drug interactions. Nucleic Acids Res. 2010 Jan;38(Database issue):D237-43. Epub 2009 Nov 24. Pubmed

4. Cytochrome P450 3A4

Kind: protein

Organism: Human

Pharmacological action: unknown

Actions: inducer

Components

Name UniProt ID Details
Cytochrome P450 3A4 P08684 Details

References:

  1. Preissner S, Kroll K, Dunkel M, Senger C, Goldsobel G, Kuzman D, Guenther S, Winnenburg R, Schroeder M, Preissner R: SuperCYP: a comprehensive database on Cytochrome P450 enzymes including a tool for analysis of CYP-drug interactions. Nucleic Acids Res. 2010 Jan;38(Database issue):D237-43. Epub 2009 Nov 24. Pubmed

1. Serum albumin

Kind: protein

Organism: Human

Pharmacological action: no

Components

Name UniProt ID Details
Serum albumin P02768 Details

References:

  1. Dundee JW, Halliday NJ, McMurray TJ: Aspirin and probenecid pretreatment influences the potency of thiopentone and the onset of action of midazolam. Eur J Anaesthesiol. 1986 May;3(3):247-51. Pubmed
  2. Gewirtz DA, Holt SA: Protein binding as a component of drug interaction in cellular pharmacokinetic studies. Effects of probenecid on transport and accumulation of methotrexate in Ehrlich ascites tumor cells in vitro. Biochem Pharmacol. 1985 Mar 15;34(6):747-54. Pubmed
  3. Hansen-Moller J, Schmit U: Rapid high-performance liquid chromatographic assay for the simultaneous determination of probenecid and its glucuronide in urine. Irreversible binding of probenecid to serum albumin. J Pharm Biomed Anal. 1991;9(1):65-73. Pubmed

1. Solute carrier family 22 member 2

Kind: protein

Organism: Human

Pharmacological action: unknown

Actions: inhibitor

Components

Name UniProt ID Details
Solute carrier family 22 member 2 O15244 Details

References:

  1. Arndt P, Volk C, Gorboulev V, Budiman T, Popp C, Ulzheimer-Teuber I, Akhoundova A, Koppatz S, Bamberg E, Nagel G, Koepsell H: Interaction of cations, anions, and weak base quinine with rat renal cation transporter rOCT2 compared with rOCT1. Am J Physiol Renal Physiol. 2001 Sep;281(3):F454-68. Pubmed

2. Solute carrier family 22 member 1

Kind: protein

Organism: Human

Pharmacological action: unknown

Actions: inhibitor

Components

Name UniProt ID Details
Solute carrier family 22 member 1 O15245 Details

References:

  1. Arndt P, Volk C, Gorboulev V, Budiman T, Popp C, Ulzheimer-Teuber I, Akhoundova A, Koppatz S, Bamberg E, Nagel G, Koepsell H: Interaction of cations, anions, and weak base quinine with rat renal cation transporter rOCT2 compared with rOCT1. Am J Physiol Renal Physiol. 2001 Sep;281(3):F454-68. Pubmed

3. Canalicular multispecific organic anion transporter 2

Kind: protein

Organism: Human

Pharmacological action: unknown

Actions: inhibitor

Components

Name UniProt ID Details
Canalicular multispecific organic anion transporter 2 O15438 Details

References:

  1. Zelcer N, Saeki T, Reid G, Beijnen JH, Borst P: Characterization of drug transport by the human multidrug resistance protein 3 (ABCC3). J Biol Chem. 2001 Dec 7;276(49):46400-7. Pubmed
  2. Zeng H, Chen ZS, Belinsky MG, Rea PA, Kruh GD: Transport of methotrexate (MTX) and folates by multidrug resistance protein (MRP) 3 and MRP1: effect of polyglutamylation on MTX transport. Cancer Res. 2001 Oct 1;61(19):7225-32. Pubmed
  3. Zamek-Gliszczynski MJ, Xiong H, Patel NJ, Turncliff RZ, Pollack GM, Brouwer KL: Pharmacokinetics of 5 (and 6)-carboxy-2’,7’-dichlorofluorescein and its diacetate promoiety in the liver. J Pharmacol Exp Ther. 2003 Feb;304(2):801-9. Pubmed

4. Multidrug resistance-associated protein 4

Kind: protein

Organism: Human

Pharmacological action: unknown

Actions: inhibitor

Components

Name UniProt ID Details
Multidrug resistance-associated protein 4 O15439 Details

References:

  1. van Aubel RA, Smeets PH, Peters JG, Bindels RJ, Russel FG: The MRP4/ABCC4 gene encodes a novel apical organic anion transporter in human kidney proximal tubules: putative efflux pump for urinary cAMP and cGMP. J Am Soc Nephrol. 2002 Mar;13(3):595-603. Pubmed
  2. Chen ZS, Lee K, Walther S, Raftogianis RB, Kuwano M, Zeng H, Kruh GD: Analysis of methotrexate and folate transport by multidrug resistance protein 4 (ABCC4): MRP4 is a component of the methotrexate efflux system. Cancer Res. 2002 Jun 1;62(11):3144-50. Pubmed
  3. Rius M, Nies AT, Hummel-Eisenbeiss J, Jedlitschky G, Keppler D: Cotransport of reduced glutathione with bile salts by MRP4 (ABCC4) localized to the basolateral hepatocyte membrane. Hepatology. 2003 Aug;38(2):374-84. Pubmed

5. Multidrug resistance-associated protein 5

Kind: protein

Organism: Human

Pharmacological action: unknown

Actions: inhibitor

Components

Name UniProt ID Details
Multidrug resistance-associated protein 5 O15440 Details

References:

  1. Jedlitschky G, Burchell B, Keppler D: The multidrug resistance protein 5 functions as an ATP-dependent export pump for cyclic nucleotides. J Biol Chem. 2000 Sep 29;275(39):30069-74. Pubmed

6. Monocarboxylate transporter 2

Kind: protein

Organism: Human

Pharmacological action: unknown

Actions: inhibitor

Components

Name UniProt ID Details
Monocarboxylate transporter 2 O60669 Details

References:

  1. Broer S, Broer A, Schneider HP, Stegen C, Halestrap AP, Deitmer JW: Characterization of the high-affinity monocarboxylate transporter MCT2 in Xenopus laevis oocytes. Biochem J. 1999 Aug 1;341 ( Pt 3):529-35. Pubmed

7. Solute carrier family 22 member 5

Kind: protein

Organism: Human

Pharmacological action: unknown

Actions: inhibitor

Components

Name UniProt ID Details
Solute carrier family 22 member 5 O76082 Details

References:

  1. Ohashi R, Tamai I, Yabuuchi H, Nezu JI, Oku A, Sai Y, Shimane M, Tsuji A: Na(+)-dependent carnitine transport by organic cation transporter (OCTN2): its pharmacological and toxicological relevance. J Pharmacol Exp Ther. 1999 Nov;291(2):778-84. Pubmed

8. Multidrug resistance-associated protein 6

Kind: protein

Organism: Human

Pharmacological action: unknown

Actions: inhibitor

Components

Name UniProt ID Details
Multidrug resistance-associated protein 6 O95255 Details

References:

  1. Ilias A, Urban Z, Seidl TL, Le Saux O, Sinko E, Boyd CD, Sarkadi B, Varadi A: Loss of ATP-dependent transport activity in pseudoxanthoma elasticum-associated mutants of human ABCC6 (MRP6). J Biol Chem. 2002 May 10;277(19):16860-7. Epub 2002 Mar 5. Pubmed

9. Multidrug resistance protein 1

Kind: protein

Organism: Human

Pharmacological action: unknown

Actions: inhibitor

Components

Name UniProt ID Details
Multidrug resistance protein 1 P08183 Details

References:

  1. Gao J, Murase O, Schowen RL, Aube J, Borchardt RT: A functional assay for quantitation of the apparent affinities of ligands of P-glycoprotein in Caco-2 cells. Pharm Res. 2001 Feb;18(2):171-6. Pubmed
  2. Honda Y, Ushigome F, Koyabu N, Morimoto S, Shoyama Y, Uchiumi T, Kuwano M, Ohtani H, Sawada Y: Effects of grapefruit juice and orange juice components on P-glycoprotein- and MRP2-mediated drug efflux. Br J Pharmacol. 2004 Dec;143(7):856-64. Epub 2004 Oct 25. Pubmed
  3. Minderman H, Brooks TA, O’Loughlin KL, Ojima I, Bernacki RJ, Baer MR: Broad-spectrum modulation of ATP-binding cassette transport proteins by the taxane derivatives ortataxel (IDN-5109, BAY 59-8862) and tRA96023. Cancer Chemother Pharmacol. 2004 May;53(5):363-9. Epub 2004 Jan 27. Pubmed

10. Multidrug resistance-associated protein 1

Kind: protein

Organism: Human

Pharmacological action: unknown

Actions: inhibitor

Components

Name UniProt ID Details
Multidrug resistance-associated protein 1 P33527 Details

References:

  1. Hong J, Lambert JD, Lee SH, Sinko PJ, Yang CS: Involvement of multidrug resistance-associated proteins in regulating cellular levels of (-)-epigallocatechin-3-gallate and its methyl metabolites. Biochem Biophys Res Commun. 2003 Oct 10;310(1):222-7. Pubmed
  2. Ilias A, Urban Z, Seidl TL, Le Saux O, Sinko E, Boyd CD, Sarkadi B, Varadi A: Loss of ATP-dependent transport activity in pseudoxanthoma elasticum-associated mutants of human ABCC6 (MRP6). J Biol Chem. 2002 May 10;277(19):16860-7. Epub 2002 Mar 5. Pubmed
  3. Payen L, Delugin L, Courtois A, Trinquart Y, Guillouzo A, Fardel O: Reversal of MRP-mediated multidrug resistance in human lung cancer cells by the antiprogestatin drug RU486. Biochem Biophys Res Commun. 1999 May 19;258(3):513-8. Pubmed
  4. Bakos E, Evers R, Sinko E, Varadi A, Borst P, Sarkadi B: Interactions of the human multidrug resistance proteins MRP1 and MRP2 with organic anions. Mol Pharmacol. 2000 Apr;57(4):760-8. Pubmed
  5. Hooijberg JH, Broxterman HJ, Kool M, Assaraf YG, Peters GJ, Noordhuis P, Scheper RJ, Borst P, Pinedo HM, Jansen G: Antifolate resistance mediated by the multidrug resistance proteins MRP1 and MRP2. Cancer Res. 1999 Jun 1;59(11):2532-5. Pubmed
  6. Legrand O, Simonin G, Beauchamp-Nicoud A, Zittoun R, Marie JP: Simultaneous activity of MRP1 and Pgp is correlated with in vitro resistance to daunorubicin and with in vivo resistance in adult acute myeloid leukemia. Blood. 1999 Aug 1;94(3):1046-56. Pubmed
  7. Legrand O, Simonin G, Perrot JY, Zittoun R, Marie JP: Both Pgp and MRP1 activities using calcein-AM contribute to drug resistance in AML. Adv Exp Med Biol. 1999;457:161-75. Pubmed
  8. Evers R, de Haas M, Sparidans R, Beijnen J, Wielinga PR, Lankelma J, Borst P: Vinblastine and sulfinpyrazone export by the multidrug resistance protein MRP2 is associated with glutathione export. Br J Cancer. 2000 Aug;83(3):375-83. Pubmed
  9. Issandou M, Grand-Perret T: Multidrug resistance P-glycoprotein is not involved in cholesterol esterification. Biochem Biophys Res Commun. 2000 Dec 20;279(2):369-77. Pubmed

11. Solute carrier organic anion transporter family member 1A2

Kind: protein

Organism: Human

Pharmacological action: unknown

Actions: inhibitor

Components

Name UniProt ID Details
Solute carrier organic anion transporter family member 1A2 P46721 Details

References:

  1. Sugiyama D, Kusuhara H, Shitara Y, Abe T, Meier PJ, Sekine T, Endou H, Suzuki H, Sugiyama Y: Characterization of the efflux transport of 17beta-estradiol-D-17beta-glucuronide from the brain across the blood-brain barrier. J Pharmacol Exp Ther. 2001 Jul;298(1):316-22. Pubmed
  2. Kullak-Ublick GA, Hagenbuch B, Stieger B, Wolkoff AW, Meier PJ: Functional characterization of the basolateral rat liver organic anion transporting polypeptide. Hepatology. 1994 Aug;20(2):411-6. Pubmed

12. Monocarboxylate transporter 1

Kind: protein

Organism: Human

Pharmacological action: unknown

Actions: inhibitor

Components

Name UniProt ID Details
Monocarboxylate transporter 1 P53985 Details

References:

  1. Broer S, Broer A, Schneider HP, Stegen C, Halestrap AP, Deitmer JW: Characterization of the high-affinity monocarboxylate transporter MCT2 in Xenopus laevis oocytes. Biochem J. 1999 Aug 1;341 ( Pt 3):529-35. Pubmed

13. Sodium/bile acid cotransporter

Kind: protein

Organism: Human

Pharmacological action: unknown

Actions: inhibitor

Components

Name UniProt ID Details
Sodium/bile acid cotransporter Q14973 Details

References:

  1. Hagenbuch B, Stieger B, Foguet M, Lubbert H, Meier PJ: Functional expression cloning and characterization of the hepatocyte Na+/bile acid cotransport system. Proc Natl Acad Sci U S A. 1991 Dec 1;88(23):10629-33. Pubmed

14. Solute carrier family 22 member 6

Kind: protein

Organism: Human

Pharmacological action: unknown

Actions: inhibitor

Components

Name UniProt ID Details
Solute carrier family 22 member 6 Q4U2R8 Details

References:

  1. Cihlar T, Ho ES: Fluorescence-based assay for the interaction of small molecules with the human renal organic anion transporter 1. Anal Biochem. 2000 Jul 15;283(1):49-55. Pubmed
  2. Mulato AS, Ho ES, Cihlar T: Nonsteroidal anti-inflammatory drugs efficiently reduce the transport and cytotoxicity of adefovir mediated by the human renal organic anion transporter 1. J Pharmacol Exp Ther. 2000 Oct;295(1):10-5. Pubmed
  3. Takeda M, Narikawa S, Hosoyamada M, Cha SH, Sekine T, Endou H: Characterization of organic anion transport inhibitors using cells stably expressing human organic anion transporters. Eur J Pharmacol. 2001 May 11;419(2-3):113-20. Pubmed
  4. Jung KY, Takeda M, Kim DK, Tojo A, Narikawa S, Yoo BS, Hosoyamada M, Cha SH, Sekine T, Endou H: Characterization of ochratoxin A transport by human organic anion transporters. Life Sci. 2001 Sep 21;69(18):2123-35. Pubmed
  5. Ichida K, Hosoyamada M, Kimura H, Takeda M, Utsunomiya Y, Hosoya T, Endou H: Urate transport via human PAH transporter hOAT1 and its gene structure. Kidney Int. 2003 Jan;63(1):143-55. Pubmed
  6. Takeda M, Khamdang S, Narikawa S, Kimura H, Hosoyamada M, Cha SH, Sekine T, Endou H: Characterization of methotrexate transport and its drug interactions with human organic anion transporters. J Pharmacol Exp Ther. 2002 Aug;302(2):666-71. Pubmed
  7. Lu R, Chan BS, Schuster VL: Cloning of the human kidney PAH transporter: narrow substrate specificity and regulation by protein kinase C. Am J Physiol. 1999 Feb;276(2 Pt 2):F295-303. Pubmed
  8. Race JE, Grassl SM, Williams WJ, Holtzman EJ: Molecular cloning and characterization of two novel human renal organic anion transporters (hOAT1 and hOAT3). Biochem Biophys Res Commun. 1999 Feb 16;255(2):508-14. Pubmed
  9. Khamdang S, Takeda M, Shimoda M, Noshiro R, Narikawa S, Huang XL, Enomoto A, Piyachaturawat P, Endou H: Interactions of human- and rat-organic anion transporters with pravastatin and cimetidine. J Pharmacol Sci. 2004 Feb;94(2):197-202. Pubmed
  10. Kuze K, Graves P, Leahy A, Wilson P, Stuhlmann H, You G: Heterologous expression and functional characterization of a mouse renal organic anion transporter in mammalian cells. J Biol Chem. 1999 Jan 15;274(3):1519-24. Pubmed
  11. Uwai Y, Saito H, Inui K: Interaction between methotrexate and nonsteroidal anti-inflammatory drugs in organic anion transporter. Eur J Pharmacol. 2000 Dec 1;409(1):31-6. Pubmed
  12. Tsuda M, Sekine T, Takeda M, Cha SH, Kanai Y, Kimura M, Endou H: Transport of ochratoxin A by renal multispecific organic anion transporter 1. J Pharmacol Exp Ther. 1999 Jun;289(3):1301-5. Pubmed
  13. Takeda M, Tojo A, Sekine T, Hosoyamada M, Kanai Y, Endou H: Role of organic anion transporter 1 (OAT1) in cephaloridine (CER)-induced nephrotoxicity. Kidney Int. 1999 Dec;56(6):2128-36. Pubmed
  14. Sugiyama D, Kusuhara H, Shitara Y, Abe T, Meier PJ, Sekine T, Endou H, Suzuki H, Sugiyama Y: Characterization of the efflux transport of 17beta-estradiol-D-17beta-glucuronide from the brain across the blood-brain barrier. J Pharmacol Exp Ther. 2001 Jul;298(1):316-22. Pubmed
  15. Uwai Y, Iwamoto K: Transport of aminopterin by human organic anion transporters hOAT1 and hOAT3: Comparison with methotrexate. Drug Metab Pharmacokinet. 2010;25(2):163-9. Pubmed

15. Solute carrier family 22 member 10

Kind: protein

Organism: Human

Pharmacological action: unknown

Actions: inhibitor

Components

Name UniProt ID Details
Solute carrier family 22 member 10 Q63ZE4 Details

References:

  1. Youngblood GL, Sweet DH: Identification and functional assessment of the novel murine organic anion transporter Oat5 (Slc22a19) expressed in kidney. Am J Physiol Renal Physiol. 2004 Aug;287(2):F236-44. Epub 2004 Apr 6. Pubmed

16. Solute carrier family 22 member 8

Kind: protein

Organism: Human

Pharmacological action: unknown

Actions: inhibitor

Components

Name UniProt ID Details
Solute carrier family 22 member 8 Q8TCC7 Details

References:

  1. Cha SH, Sekine T, Fukushima JI, Kanai Y, Kobayashi Y, Goya T, Endou H: Identification and characterization of human organic anion transporter 3 expressing predominantly in the kidney. Mol Pharmacol. 2001 May;59(5):1277-86. Pubmed
  2. Takeda M, Narikawa S, Hosoyamada M, Cha SH, Sekine T, Endou H: Characterization of organic anion transport inhibitors using cells stably expressing human organic anion transporters. Eur J Pharmacol. 2001 May 11;419(2-3):113-20. Pubmed
  3. Jung KY, Takeda M, Kim DK, Tojo A, Narikawa S, Yoo BS, Hosoyamada M, Cha SH, Sekine T, Endou H: Characterization of ochratoxin A transport by human organic anion transporters. Life Sci. 2001 Sep 21;69(18):2123-35. Pubmed
  4. Takeda M, Khamdang S, Narikawa S, Kimura H, Hosoyamada M, Cha SH, Sekine T, Endou H: Characterization of methotrexate transport and its drug interactions with human organic anion transporters. J Pharmacol Exp Ther. 2002 Aug;302(2):666-71. Pubmed
  5. Khamdang S, Takeda M, Shimoda M, Noshiro R, Narikawa S, Huang XL, Enomoto A, Piyachaturawat P, Endou H: Interactions of human- and rat-organic anion transporters with pravastatin and cimetidine. J Pharmacol Sci. 2004 Feb;94(2):197-202. Pubmed
  6. Ohtsuki S, Kikkawa T, Mori S, Hori S, Takanaga H, Otagiri M, Terasaki T: Mouse reduced in osteosclerosis transporter functions as an organic anion transporter 3 and is localized at abluminal membrane of blood-brain barrier. J Pharmacol Exp Ther. 2004 Jun;309(3):1273-81. Epub 2004 Feb 4. Pubmed
  7. Mori S, Takanaga H, Ohtsuki S, Deguchi T, Kang YS, Hosoya K, Terasaki T: Rat organic anion transporter 3 (rOAT3) is responsible for brain-to-blood efflux of homovanillic acid at the abluminal membrane of brain capillary endothelial cells. J Cereb Blood Flow Metab. 2003 Apr;23(4):432-40. Pubmed
  8. Kusuhara H, Sekine T, Utsunomiya-Tate N, Tsuda M, Kojima R, Cha SH, Sugiyama Y, Kanai Y, Endou H: Molecular cloning and characterization of a new multispecific organic anion transporter from rat brain. J Biol Chem. 1999 May 7;274(19):13675-80. Pubmed
  9. Sugiyama D, Kusuhara H, Shitara Y, Abe T, Meier PJ, Sekine T, Endou H, Suzuki H, Sugiyama Y: Characterization of the efflux transport of 17beta-estradiol-D-17beta-glucuronide from the brain across the blood-brain barrier. J Pharmacol Exp Ther. 2001 Jul;298(1):316-22. Pubmed
  10. Nagata Y, Kusuhara H, Endou H, Sugiyama Y: Expression and functional characterization of rat organic anion transporter 3 (rOat3) in the choroid plexus. Mol Pharmacol. 2002 May;61(5):982-8. Pubmed
  11. Uwai Y, Iwamoto K: Transport of aminopterin by human organic anion transporters hOAT1 and hOAT3: Comparison with methotrexate. Drug Metab Pharmacokinet. 2010;25(2):163-9. Pubmed
  12. Lai Y, Sampson KE, Balogh LM, Brayman TG, Cox SR, Adams WJ, Kumar V, Stevens JC: Preclinical and clinical evidence for the collaborative transport and renal secretion of an oxazolidinone antibiotic by organic anion transporter 3 (OAT3/SLC22A8) and multidrug and toxin extrusion protein 1 (MATE1/SLC47A1). J Pharmacol Exp Ther. 2010 Sep 1;334(3):936-44. Epub 2010 Jun 2. Pubmed

17. Canalicular multispecific organic anion transporter 1

Kind: protein

Organism: Human

Pharmacological action: unknown

Actions: substrate inhibitor

Components

Name UniProt ID Details
Canalicular multispecific organic anion transporter 1 Q92887 Details

References:

  1. Hong J, Lambert JD, Lee SH, Sinko PJ, Yang CS: Involvement of multidrug resistance-associated proteins in regulating cellular levels of (-)-epigallocatechin-3-gallate and its methyl metabolites. Biochem Biophys Res Commun. 2003 Oct 10;310(1):222-7. Pubmed
  2. Ilias A, Urban Z, Seidl TL, Le Saux O, Sinko E, Boyd CD, Sarkadi B, Varadi A: Loss of ATP-dependent transport activity in pseudoxanthoma elasticum-associated mutants of human ABCC6 (MRP6). J Biol Chem. 2002 May 10;277(19):16860-7. Epub 2002 Mar 5. Pubmed
  3. Bakos E, Evers R, Sinko E, Varadi A, Borst P, Sarkadi B: Interactions of the human multidrug resistance proteins MRP1 and MRP2 with organic anions. Mol Pharmacol. 2000 Apr;57(4):760-8. Pubmed
  4. Horikawa M, Kato Y, Tyson CA, Sugiyama Y: The potential for an interaction between MRP2 (ABCC2) and various therapeutic agents: probenecid as a candidate inhibitor of the biliary excretion of irinotecan metabolites. Drug Metab Pharmacokinet. 2002;17(1):23-33. Pubmed
  5. Zamek-Gliszczynski MJ, Xiong H, Patel NJ, Turncliff RZ, Pollack GM, Brouwer KL: Pharmacokinetics of 5 (and 6)-carboxy-2’,7’-dichlorofluorescein and its diacetate promoiety in the liver. J Pharmacol Exp Ther. 2003 Feb;304(2):801-9. Pubmed
  6. Dahan A, Sabit H, Amidon GL: The H2 receptor antagonist nizatidine is a P-glycoprotein substrate: characterization of its intestinal epithelial cell efflux transport. AAPS J. 2009 Jun;11(2):205-13. Epub 2009 Mar 25. Pubmed
  7. Chen C, Scott D, Hanson E, Franco J, Berryman E, Volberg M, Liu X: Impact of Mrp2 on the biliary excretion and intestinal absorption of furosemide, probenecid, and methotrexate using Eisai hyperbilirubinemic rats. Pharm Res. 2003 Jan;20(1):31-7. Pubmed

18. ATP-binding cassette sub-family C member 11

Kind: protein

Organism: Human

Pharmacological action: unknown

Actions: inhibitor

Components

Name UniProt ID Details
ATP-binding cassette sub-family C member 11 Q96J66 Details

References:

  1. Chen ZS, Guo Y, Belinsky MG, Kotova E, Kruh GD: Transport of bile acids, sulfated steroids, estradiol 17-beta-D-glucuronide, and leukotriene C4 by human multidrug resistance protein 8 (ABCC11). Mol Pharmacol. 2005 Feb;67(2):545-57. Epub 2004 Nov 10. Pubmed

19. Solute carrier family 22 member 11

Kind: protein

Organism: Human

Pharmacological action: unknown

Actions: inhibitor

Components

Name UniProt ID Details
Solute carrier family 22 member 11 Q9NSA0 Details

References:

  1. Enomoto A, Takeda M, Shimoda M, Narikawa S, Kobayashi Y, Kobayashi Y, Yamamoto T, Sekine T, Cha SH, Niwa T, Endou H: Interaction of human organic anion transporters 2 and 4 with organic anion transport inhibitors. J Pharmacol Exp Ther. 2002 Jun;301(3):797-802. Pubmed
  2. Babu E, Takeda M, Narikawa S, Kobayashi Y, Enomoto A, Tojo A, Cha SH, Sekine T, Sakthisekaran D, Endou H: Role of human organic anion transporter 4 in the transport of ochratoxin A. Biochim Biophys Acta. 2002 Jun 12;1590(1-3):64-75. Pubmed
  3. Takeda M, Khamdang S, Narikawa S, Kimura H, Hosoyamada M, Cha SH, Sekine T, Endou H: Characterization of methotrexate transport and its drug interactions with human organic anion transporters. J Pharmacol Exp Ther. 2002 Aug;302(2):666-71. Pubmed
  4. Khamdang S, Takeda M, Shimoda M, Noshiro R, Narikawa S, Huang XL, Enomoto A, Piyachaturawat P, Endou H: Interactions of human- and rat-organic anion transporters with pravastatin and cimetidine. J Pharmacol Sci. 2004 Feb;94(2):197-202. Pubmed

20. Solute carrier organic anion transporter family member 1C1

Kind: protein

Organism: Human

Pharmacological action: unknown

Actions: inhibitor

Components

Name UniProt ID Details
Solute carrier organic anion transporter family member 1C1 Q9NYB5 Details

References:

  1. Tohyama K, Kusuhara H, Sugiyama Y: Involvement of multispecific organic anion transporter, Oatp14 (Slc21a14), in the transport of thyroxine across the blood-brain barrier. Endocrinology. 2004 Sep;145(9):4384-91. Epub 2004 May 27. Pubmed

21. Solute carrier family 22 member 7

Kind: protein

Organism: Human

Pharmacological action: unknown

Actions: inhibitor

Components

Name UniProt ID Details
Solute carrier family 22 member 7 Q9Y694 Details

References:

  1. Enomoto A, Takeda M, Shimoda M, Narikawa S, Kobayashi Y, Kobayashi Y, Yamamoto T, Sekine T, Cha SH, Niwa T, Endou H: Interaction of human organic anion transporters 2 and 4 with organic anion transport inhibitors. J Pharmacol Exp Ther. 2002 Jun;301(3):797-802. Pubmed
  2. Khamdang S, Takeda M, Shimoda M, Noshiro R, Narikawa S, Huang XL, Enomoto A, Piyachaturawat P, Endou H: Interactions of human- and rat-organic anion transporters with pravastatin and cimetidine. J Pharmacol Sci. 2004 Feb;94(2):197-202. Pubmed

22. Solute carrier family 22 member 12

Kind: protein

Organism: Human

Pharmacological action: unknown

Actions: inhibitor

Components

Name UniProt ID Details
Solute carrier family 22 member 12 Q96S37 Details

References:

  1. Shin HJ, Takeda M, Enomoto A, Fujimura M, Miyazaki H, Anzai N, Endou H: Interactions of urate transporter URAT1 in human kidney with uricosuric drugs. Nephrology (Carlton). 2011 Feb;16(2):156-62. doi: 10.1111/j.1440-1797.2010.01368.×. Pubmed

23. Solute carrier family 2, facilitated glucose transporter member 9

Kind: protein

Organism: Human

Pharmacological action: unknown

Actions: inhibitor

Components

Name UniProt ID Details
Solute carrier family 2, facilitated glucose transporter member 9 Q9NRM0 Details

References:

  1. http://www.pharmgkb.org/pathway/PA165980774

Comments
Drug created on June 13, 2005 07:24 / Updated on September 16, 2013 17:13