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Identification
NameSulfinpyrazone
Accession NumberDB01138  (APRD00620)
Typesmall molecule
Groupsapproved
Description

A uricosuric drug that is used to reduce the serum urate levels in gout therapy. It lacks anti-inflammatory, analgesic, and diuretic properties. [PubChem]

Structure
Thumb
Synonyms
SynonymLanguageCode
SulfoxyphenylpyrazolidineNot AvailableNot Available
SaltsNot Available
Brand names
NameCompany
AnturaneNot Available
Brand mixturesNot Available
Categories
CAS number57-96-5
WeightAverage: 404.482
Monoisotopic: 404.119463206
Chemical FormulaC23H20N2O3S
InChI KeyInChIKey=MBGGBVCUIVRRBF-UHFFFAOYSA-N
InChI
InChI=1S/C23H20N2O3S/c26-22-21(16-17-29(28)20-14-8-3-9-15-20)23(27)25(19-12-6-2-7-13-19)24(22)18-10-4-1-5-11-18/h1-15,21H,16-17H2
IUPAC Name
4-[2-(benzenesulfinyl)ethyl]-1,2-diphenylpyrazolidine-3,5-dione
SMILES
O=C1C(CCS(=O)C2=CC=CC=C2)C(=O)N(N1C1=CC=CC=C1)C1=CC=CC=C1
Mass SpecNot Available
Taxonomy
KingdomOrganic Compounds
SuperclassBenzenoids
ClassBenzene and Substituted Derivatives
SubclassNot Available
Direct parentBenzene and Substituted Derivatives
Alternative parentsPyrazolidinones; Sulfoxides; Carboxylic Acid Hydrazides; Polyamines; Carboxylic Acid Amides; Hydrazines and Derivatives
Substituentspyrazolidine; carboxylic acid hydrazide; carboxamide group; sulfoxide; carboxylic acid derivative; polyamine; hydrazine derivative; amine; organonitrogen compound
Classification descriptionThis compound belongs to the benzene and substituted derivatives. These are aromatic compounds containing at least one benzene ring.
Pharmacology
IndicationFor the treatment of gout and gouty arthritis.
PharmacodynamicsSulfinpyrazone's pharmacologic activity is the potentiation of the urinary excretion of uric acid. It is useful for reducing the blood urate levels in patients with chronic tophaceous gout and acute intermittent gout, and for promoting the resorption of tophi.
Mechanism of actionSulfinpyrazone is an oral uricosuric agent (pyrazolone derivative) used to treat chronic or intermittent gouty arthritis. Sulfinpyrazone competitively inhibits the reabsorption of uric acid at the proximal convoluted tubule, thereby facilitating urinary excretion of uric acid and decreasing plasma urate concentrations. This is likely done through inhibition of the urate anion transporter (hURAT1) as well as the human organic anion transporter 4 (hOAT4). Sulfinpyrazone is not intended for the treatment of acute attacks because it lacks therapeutically useful analgesic and anti-inflammatory effects. Sulfinpyrazone and its sulfide metabolite possess COX inhibitory effects. Sulfinpyrazone has also been shown to be a UDP-glucuronsyltransferase inhibitor and a very potent CYP2C9 inhibitor. Sulfinpyrazone is also known to be a cystic fibrosis transmembrane conductance regulator (CFTR) inhibitor as well as an inhibitor of several multridrug resistance proteins (MRPs).
AbsorptionNot Available
Volume of distributionNot Available
Protein binding98-99%
Metabolism
SubstrateEnzymesProduct
Sulfinpyrazone
Sulfinpyrazone sulfideDetails
Sulfinpyrazone
Sulfinpyrazone sulfoneDetails
Route of eliminationNot Available
Half lifeApproximately 4-6 hours
ClearanceNot Available
ToxicitySymptoms of overdose include nausea, vomiting, diarrhea, epigastric pain, ataxia, labored respiration, convulsions, coma. Possible symptoms, seen after overdosage with other pyrazolone derivatives: anemia, jaundice, and ulceration.
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 + 0.9961
Blood Brain Barrier + 0.9776
Caco-2 permeable - 0.5583
P-glycoprotein substrate Non-substrate 0.9163
P-glycoprotein inhibitor I Non-inhibitor 0.858
P-glycoprotein inhibitor II Non-inhibitor 0.6257
Renal organic cation transporter Non-inhibitor 0.8111
CYP450 2C9 substrate Non-substrate 0.5504
CYP450 2D6 substrate Non-substrate 0.8878
CYP450 3A4 substrate Substrate 0.5146
CYP450 1A2 substrate Non-inhibitor 0.9045
CYP450 2C9 substrate Inhibitor 0.8949
CYP450 2D6 substrate Non-inhibitor 0.9231
CYP450 2C19 substrate Non-inhibitor 0.9026
CYP450 3A4 substrate Inhibitor 0.796
CYP450 inhibitory promiscuity Low CYP Inhibitory Promiscuity 0.6332
Ames test Non AMES toxic 0.6195
Carcinogenicity Non-carcinogens 0.6932
Biodegradation Not ready biodegradable 0.9577
Rat acute toxicity 3.0218 LD50, mol/kg Not applicable
hERG inhibition (predictor I) Weak inhibitor 0.9712
hERG inhibition (predictor II) Non-inhibitor 0.8418
Pharmacoeconomics
Manufacturers
  • Novartis pharmaceuticals corp
  • Barr laboratories inc
  • Ivax pharmaceuticals inc
  • Par pharmaceutical inc
  • Vangard laboratories inc div midway medical co
  • Watson laboratories inc
Packagers
Dosage forms
FormRouteStrength
TabletOral
Prices
Unit descriptionCostUnit
Apo-Sulfinpyrazone 200 mg Tablet0.31USDtablet
DrugBank does not sell nor buy drugs. Pricing information is supplied for informational purposes only.
PatentsNot Available
Properties
Statesolid
Experimental Properties
PropertyValueSource
melting point136-137 °CPhysProp
water solubility31.2 mg/LNot Available
logP2.30HANSCH,C ET AL. (1995)
pKa3.25SANGSTER (1994)
Predicted Properties
PropertyValueSource
water solubility3.23e-01 g/lALOGPS
logP2.92ALOGPS
logP3.19ChemAxon
logS-3.1ALOGPS
pKa (strongest acidic)3.41ChemAxon
pKa (strongest basic)-6.7ChemAxon
physiological charge-1ChemAxon
hydrogen acceptor count3ChemAxon
hydrogen donor count0ChemAxon
polar surface area57.69ChemAxon
rotatable bond count6ChemAxon
refractivity113.62ChemAxon
polarizability42.15ChemAxon
number of rings4ChemAxon
bioavailability1ChemAxon
rule of fiveYesChemAxon
Ghose filterYesChemAxon
Veber's ruleNoChemAxon
MDDR-like ruleYesChemAxon
Spectra
SpectraNot Available
References
Synthesis ReferenceNot Available
General ReferenceNot Available
External Links
ResourceLink
KEGG DrugD00449
KEGG CompoundC07317
PubChem Compound5342
PubChem Substance46504918
ChemSpider5149
ChEBI9342
ChEMBLCHEMBL832
Therapeutic Targets DatabaseDAP000794
PharmGKBPA451550
Drug Product Database441759
RxListhttp://www.rxlist.com/cgi/generic3/sulfinpyrazone.htm
Drugs.comhttp://www.drugs.com/mtm/sulfinpyrazone.html
WikipediaSulfinpyrazone
ATC CodesM04AB02
AHFS Codes
  • 40:40.00
PDB EntriesNot Available
FDA labelNot Available
MSDSNot Available
Interactions
Drug Interactions
Drug
CyclosporineSulfinpyrazone decreases the effect of cyclosporine
TolbutamideTolbutamide, a strong CYP2C9 inhibitor, may decrease the metabolism and clearance of Sulfinpyrazone. Consider alternate therapy or monitor for changes in Sulfinpyrazone therapeutic and adverse effects if Tolbutamide is initiated, discontinued or dose changed.
WarfarinSulfinpyrazone may increase the anticoagulant effect of warfarin by decreasing its metabolism and protein binding.
Food InteractionsNot Available

1. Canalicular multispecific organic anion transporter 1

Kind: protein

Organism: Human

Pharmacological action: yes

Actions: inhibitor

Components

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

References:

  1. 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
  2. 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
  3. Morrow CS, Smitherman PK, Townsend AJ: Role of multidrug-resistance protein 2 in glutathione S-transferase P1-1-mediated resistance to 4-nitroquinoline 1-oxide toxicities in HepG2 cells. Mol Carcinog. 2000 Nov;29(3):170-8. Pubmed
  4. Ito K, Oleschuk CJ, Westlake C, Vasa MZ, Deeley RG, Cole SP: Mutation of Trp1254 in the multispecific organic anion transporter, multidrug resistance protein 2 (MRP2) (ABCC2), alters substrate specificity and results in loss of methotrexate transport activity. J Biol Chem. 2001 Oct 12;276(41):38108-14. Epub 2001 Aug 10. Pubmed
  5. Flanagan SD, Cummins CL, Susanto M, Liu X, Takahashi LH, Benet LZ: Comparison of furosemide and vinblastine secretion from cell lines overexpressing multidrug resistance protein (P-glycoprotein) and multidrug resistance-associated proteins (MRP1 and MRP2). Pharmacology. 2002;64(3):126-34. Pubmed
  6. Hagos Y, Stein D, Ugele B, Burckhardt G, Bahn A: Human renal organic anion transporter 4 operates as an asymmetric urate transporter. J Am Soc Nephrol. 2007 Feb;18(2):430-9. Epub 2007 Jan 17. Pubmed

2. Multidrug resistance-associated protein 1

Kind: protein

Organism: Human

Pharmacological action: yes

Actions: inhibitor

Components

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

References:

  1. 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
  2. Morrow CS, Smitherman PK, Diah SK, Schneider E, Townsend AJ: Coordinated action of glutathione S-transferases (GSTs) and multidrug resistance protein 1 (MRP1) in antineoplastic drug detoxification. Mechanism of GST A1-1- and MRP1-associated resistance to chlorambucil in MCF7 breast carcinoma cells. J Biol Chem. 1998 Aug 7;273(32):20114-20. 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. Depeille P, Cuq P, Mary S, Passagne I, Evrard A, Cupissol D, Vian L: Glutathione S-transferase M1 and multidrug resistance protein 1 act in synergy to protect melanoma cells from vincristine effects. Mol Pharmacol. 2004 Apr;65(4):897-905. Pubmed
  5. Raggers RJ, van Helvoort A, Evers R, van Meer G: The human multidrug resistance protein MRP1 translocates sphingolipid analogs across the plasma membrane. J Cell Sci. 1999 Feb;112 ( Pt 3):415-22. Pubmed
  6. Chen X, Ji ZL, Chen YZ: TTD: Therapeutic Target Database. Nucleic Acids Res. 2002 Jan 1;30(1):412-5. Pubmed

1. Cytochrome P450 2C9

Kind: protein

Organism: Human

Pharmacological action: unknown

Actions: substrate inhibitor

Components

Name UniProt ID Details
Cytochrome P450 2C9 P11712 Details

References:

  1. Zhou SF, Zhou ZW, Yang LP, Cai JP: Substrates, inducers, inhibitors and structure-activity relationships of human Cytochrome P450 2C9 and implications in drug development. Curr Med Chem. 2009;16(27):3480-675. Epub 2009 Sep 1. Pubmed
  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 3A4

Kind: protein

Organism: Human

Pharmacological action: unknown

Actions: substrate inhibitor inducer

Components

Name UniProt ID Details
Cytochrome P450 3A4 P08684 Details

References:

  1. Zhou SF, Zhou ZW, Yang LP, Cai JP: Substrates, inducers, inhibitors and structure-activity relationships of human Cytochrome P450 2C9 and implications in drug development. Curr Med Chem. 2009;16(27):3480-675. Epub 2009 Sep 1. Pubmed
  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 2B6

Kind: protein

Organism: Human

Pharmacological action: unknown

Actions: inducer

Components

Name UniProt ID Details
Cytochrome P450 2B6 P20813 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 2C8

Kind: protein

Organism: Human

Pharmacological action: unknown

Actions: substrate

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

1. Fatty acid-binding protein, intestinal

Kind: protein

Organism: Human

Pharmacological action: no

Components

Name UniProt ID Details
Fatty acid-binding protein, intestinal P12104 Details

References:

  1. Rowland A, Knights KM, Mackenzie PI, Miners JO: Characterization of the binding of drugs to human intestinal fatty acid binding protein (IFABP): potential role of IFABP as an alternative to albumin for in vitro-in vivo extrapolation of drug kinetic parameters. Drug Metab Dispos. 2009 Jul;37(7):1395-403. Epub 2009 Apr 27. Pubmed

1. 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. 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. 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. 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. Wijnholds J, Mol CA, van Deemter L, de Haas M, Scheffer GL, Baas F, Beijnen JH, Scheper RJ, Hatse S, De Clercq E, Balzarini J, Borst P: Multidrug-resistance protein 5 is a multispecific organic anion transporter able to transport nucleotide analogs. Proc Natl Acad Sci U S A. 2000 Jun 20;97(13):7476-81. Pubmed

4. 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. Chen ZS, Hopper-Borge E, Belinsky MG, Shchaveleva I, Kotova E, Kruh GD: Characterization of the transport properties of human multidrug resistance protein 7 (MRP7, ABCC10). Mol Pharmacol. 2003 Feb;63(2):351-8. Pubmed

5. 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. 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

6. 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. 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

7. 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. Flanagan SD, Cummins CL, Susanto M, Liu X, Takahashi LH, Benet LZ: Comparison of furosemide and vinblastine secretion from cell lines overexpressing multidrug resistance protein (P-glycoprotein) and multidrug resistance-associated proteins (MRP1 and MRP2). Pharmacology. 2002;64(3):126-34. Pubmed
  2. 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

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