Pentosan Polysulfate

Identification

Name
Pentosan Polysulfate
Accession Number
DB00686  (APRD01175)
Type
Small Molecule
Groups
Approved
Description

A sulfated pentosyl polysaccharide with heparin-like properties. [PubChem]

Structure
Thumb
Synonyms
  • Pentosan sulfuric polyester
  • Pentosane polysulfate
  • Pentosani polysulfas
  • Pentosano polisulfato
  • Pentosanpolysulfat
External IDs
CB-8061 / PZ 68 / SP 54 / UNII-F59P8B75R4
Product Ingredients
IngredientUNIICASInChI Key
Calcium pentosan polysulfateNot AvailableNot AvailableNot applicable
Pentosan polysulfate sodium914032762Y140207-93-8Not applicable
Product Images
Prescription Products
NameDosageStrengthRouteLabellerMarketing StartMarketing End
ElmironCapsule, gelatin coated100 mg/1OralCardinal Health1996-09-26Not applicableUs55154 055320180907 15195 1uti8qj
ElmironCapsule100 mgOralJanssen Pharmaceuticals1993-12-31Not applicableCanada
ElmironCapsule, gelatin coated100 mg/1OralJanssen Pharmaceuticals, Inc.1996-09-26Not applicableUs50458 0098 01 nlmimage10 2a15954c
ElmironCapsule, gelatin coated100 mg/1OralOrtho Mc Neil Pharmaceuticals1996-09-262012-05-31Us
ElmironCapsule100 mg/1OralOrtho-McNeil Pharmaceutical, Inc.2006-10-172006-10-17Us
ElmironCapsule, gelatin coated100 mg/1OralPhysicians Total Care, Inc.2003-12-17Not applicableUs54868 452520180906 25352 1x5s8ge
International/Other Brands
Comfora (Swati Spentose Pvt. Ltd.) / Fibrase (Teofarma) / Fibrezym (Bene) / Hemoclar (Sanofi Winthrop) / Hémoclar (Sanofi-Aventis) / Tavan-SP (Sanofi-Aventis) / Thrombocid (Bene-Chemie)
Categories
UNII
F59P8B75R4
CAS number
37300-21-3
Weight
Average: 602.497
Monoisotopic: 601.922340398
Chemical Formula
C10H18O21S4
InChI Key
FCCNSUIJIOOXEZ-SJYYZXOBSA-N
InChI
InChI=1S/C10H18O21S4/c11-3-1-26-10(8(31-35(22,23)24)5(3)28-32(13,14)15)27-4-2-25-9(12)7(30-34(19,20)21)6(4)29-33(16,17)18/h3-12H,1-2H2,(H,13,14,15)(H,16,17,18)(H,19,20,21)(H,22,23,24)/t3-,4-,5+,6+,7-,8-,9-,10+/m1/s1
IUPAC Name
[(2S,3R,4S,5R)-5-hydroxy-2-{[(3R,4S,5R,6R)-6-hydroxy-4,5-bis(sulfooxy)oxan-3-yl]oxy}-4-(sulfooxy)oxan-3-yl]oxidanesulfonic acid
SMILES
O[C@@H]1CO[C@@H](O[C@@H]2CO[C@@H](O)[C@H](OS(O)(=O)=O)[C@H]2OS(O)(=O)=O)[C@H](OS(O)(=O)=O)[C@H]1OS(O)(=O)=O

Pharmacology

Indication

For the relief of bladder pain or discomfort associated with interstitial cystitis.

Associated Conditions
Pharmacodynamics

Pentosan polysulfate sodium is a low molecular weight heparin-like compound. It has anticoagulant and fibrinolytic effects.

Mechanism of action

Pentosan polysulfate is a polymer of xylose hydrogen sulfate and contains two sulfate groups per carbohydrate monomer. It binds Fibroblast growth factors (FGFs) as well as other heparin-binding growth factors. It has been shown to interact also with the heparin-binding site of FGFR-1. It inhibits the growth of SW13 adrenocortical cells transfected with FGF-4 and tumorigenicity of MCF-7 breast carcinoma cells transfected with FGF-1 or FGF-4.

TargetActionsOrganism
AFibroblast growth factor 2
antagonist
Human
AFibroblast growth factor 1
antagonist
Human
UFibroblast growth factor 4
inhibitor
Human
Absorption

Slow

Volume of distribution
Not Available
Protein binding
Not Available
Metabolism
Not Available
Route of elimination
Not Available
Half life

4.8 hours

Clearance
Not Available
Toxicity
Not Available
Affected organisms
  • Humans and other mammals
Pathways
Not Available
Pharmacogenomic Effects/ADRs
Not Available

Interactions

Drug Interactions
DrugInteraction
(1,2,6,7-3H)TestosteroneThe therapeutic efficacy of Pentosan Polysulfate can be increased when used in combination with (1,2,6,7-3H)Testosterone.
(R)-warfarinPentosan Polysulfate may increase the anticoagulant activities of (R)-warfarin.
(S)-WarfarinPentosan Polysulfate may increase the anticoagulant activities of (S)-Warfarin.
1-TestosteroneThe therapeutic efficacy of Pentosan Polysulfate can be increased when used in combination with 1-Testosterone.
18-methyl-19-nortestosteroneThe therapeutic efficacy of Pentosan Polysulfate can be increased when used in combination with 18-methyl-19-nortestosterone.
4-hydroxycoumarinPentosan Polysulfate may increase the anticoagulant activities of 4-hydroxycoumarin.
4-HydroxytestosteroneThe therapeutic efficacy of Pentosan Polysulfate can be increased when used in combination with 4-Hydroxytestosterone.
5beta-dihydrotestosteroneThe therapeutic efficacy of Pentosan Polysulfate can be increased when used in combination with 5beta-dihydrotestosterone.
AbciximabThe risk or severity of adverse effects can be increased when Pentosan Polysulfate is combined with Abciximab.
AceclofenacThe risk or severity of bleeding and hemorrhage can be increased when Aceclofenac is combined with Pentosan Polysulfate.
Food Interactions
  • Take on an empty stomach, 1 hour before or 2 hours after meals.

References

Synthesis Reference

Pandurang Balwant Deshpande, Parvenkumar Luthra, Anand Kumar Pandey, Dinesh Jayntibhai Paghdar, Phani,Sharma,Gowthamaiah Vemavarapu Govardhana, "PROCESS FOR THE PREPARATION OF PENTOSAN POLYSULFATE OR SALTS THEREOF." U.S. Patent US20100105889, issued April 29, 2010.

US20100105889
General References
  1. Ghosh P, Smith M: Osteoarthritis, genetic and molecular mechanisms. Biogerontology. 2002;3(1-2):85-8. [PubMed:12014849]
External Links
Human Metabolome Database
HMDB0014824
PubChem Compound
37720
PubChem Substance
46509187
ChemSpider
34595
Therapeutic Targets Database
DAP001025
PharmGKB
PA164774806
RxList
RxList Drug Page
ATC Codes
C05BA04 — Pentosan polysulfate sodiumG04BX15 — Pentosan polysulfate sodium
AHFS Codes
  • 92:00.00 — Miscellaneous Therapeutic Agents
FDA label
Download (59.2 KB)

Clinical Trials

Clinical Trials
PhaseStatusPurposeConditionsCount
2CompletedTreatmentProstatitis1
2Enrolling by InvitationTreatmentBipolar Disorder (BD) / Psychotic Disorder NOS / Schizoaffective Disorders / Schizophrenic Disorders1
2Not Yet RecruitingPreventionBCG / Bladder Carcinoma / Lower Urinary Tract Symptoms (LUTS)1
3CompletedSupportive CareRadiation Enteritis / Severe or persistent diarrhea1
4TerminatedTreatmentInterstitial Cystitis1

Pharmacoeconomics

Manufacturers
  • Ortho mcneil janssen pharmaceuticals inc
Packagers
  • Alza Corp.
  • A-S Medication Solutions LLC
  • Ivax Pharmaceuticals
  • Janssen-Ortho Inc.
  • McNeil Laboratories
  • Murfreesboro Pharmaceutical Nursing Supply
  • Ortho Mcneil Janssen Pharmaceutical Inc.
  • Physicians Total Care Inc.
Dosage forms
FormRouteStrength
CapsuleOral100 mg
CapsuleOral100 mg/1
Capsule, gelatin coatedOral100 mg/1
Prices
Unit descriptionCostUnit
Elmiron 100 mg capsule3.32USD capsule
DrugBank does not sell nor buy drugs. Pricing information is supplied for informational purposes only.
Patents
Patent NumberPediatric ExtensionApprovedExpires (estimated)
US5180715No1993-01-192010-01-19Us

Properties

State
Solid
Experimental Properties
PropertyValueSource
logP-8Not Available
Predicted Properties
PropertyValueSource
Water Solubility3.49 mg/mLALOGPS
logP-2.5ALOGPS
logP-11ChemAxon
logS-2.2ALOGPS
pKa (Strongest Acidic)-2.9ChemAxon
pKa (Strongest Basic)-3.6ChemAxon
Physiological Charge-4ChemAxon
Hydrogen Acceptor Count17ChemAxon
Hydrogen Donor Count6ChemAxon
Polar Surface Area322.55 Å2ChemAxon
Rotatable Bond Count10ChemAxon
Refractivity96.38 m3·mol-1ChemAxon
Polarizability46.17 Å3ChemAxon
Number of Rings2ChemAxon
Bioavailability0ChemAxon
Rule of FiveNoChemAxon
Ghose FilterNoChemAxon
Veber's RuleNoChemAxon
MDDR-like RuleNoChemAxon
Predicted ADMET features
PropertyValueProbability
Human Intestinal Absorption-0.5
Blood Brain Barrier+0.8606
Caco-2 permeable-0.6462
P-glycoprotein substrateNon-substrate0.7185
P-glycoprotein inhibitor IInhibitor0.6326
P-glycoprotein inhibitor IINon-inhibitor0.9889
Renal organic cation transporterNon-inhibitor0.8869
CYP450 2C9 substrateNon-substrate0.9008
CYP450 2D6 substrateNon-substrate0.8275
CYP450 3A4 substrateNon-substrate0.6053
CYP450 1A2 substrateNon-inhibitor0.8007
CYP450 2C9 inhibitorNon-inhibitor0.8387
CYP450 2D6 inhibitorNon-inhibitor0.8982
CYP450 2C19 inhibitorNon-inhibitor0.8044
CYP450 3A4 inhibitorNon-inhibitor0.9891
CYP450 inhibitory promiscuityLow CYP Inhibitory Promiscuity0.964
Ames testNon AMES toxic0.6383
CarcinogenicityNon-carcinogens0.5703
BiodegradationNot ready biodegradable0.8772
Rat acute toxicity2.3876 LD50, mol/kg Not applicable
hERG inhibition (predictor I)Weak inhibitor0.8908
hERG inhibition (predictor II)Non-inhibitor0.7929
ADMET data is predicted using admetSAR, a free tool for evaluating chemical ADMET properties. (23092397)

Spectra

Mass Spec (NIST)
Not Available
Spectra
SpectrumSpectrum TypeSplash Key
Predicted GC-MS Spectrum - GC-MSPredicted GC-MSNot Available
Predicted MS/MS Spectrum - 10V, Positive (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 20V, Positive (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 40V, Positive (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 10V, Negative (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 20V, Negative (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 40V, Negative (Annotated)Predicted LC-MS/MSNot Available

Taxonomy

Description
This compound belongs to the class of organic compounds known as o-glycosyl compounds. These are glycoside in which a sugar group is bonded through one carbon to another group via a O-glycosidic bond.
Kingdom
Organic compounds
Super Class
Organic oxygen compounds
Class
Organooxygen compounds
Sub Class
Carbohydrates and carbohydrate conjugates
Direct Parent
O-glycosyl compounds
Alternative Parents
Disaccharides / Sulfuric acid monoesters / Oxanes / Alkyl sulfates / Secondary alcohols / Hemiacetals / Oxacyclic compounds / Acetals / Organic oxides / Hydrocarbon derivatives
Substituents
Disaccharide / O-glycosyl compound / Oxane / Sulfuric acid ester / Alkyl sulfate / Sulfate-ester / Sulfuric acid monoester / Organic sulfuric acid or derivatives / Hemiacetal / Secondary alcohol
Molecular Framework
Aliphatic heteromonocyclic compounds
External Descriptors
Not Available

Targets

Kind
Protein
Organism
Human
Pharmacological action
Yes
Actions
Antagonist
General Function
Ligand-dependent nuclear receptor transcription coactivator activity
Specific Function
Plays an important role in the regulation of cell survival, cell division, angiogenesis, cell differentiation and cell migration. Functions as potent mitogen in vitro.
Gene Name
FGF2
Uniprot ID
P09038
Uniprot Name
Fibroblast growth factor 2
Molecular Weight
30769.715 Da
References
  1. Zugmaier G, Favoni R, Jaeger R, Rosen N, Knabbe C: Polysulfated heparinoids selectively inactivate heparin-binding angiogenesis factors. Ann N Y Acad Sci. 1999;886:243-8. [PubMed:10667230]
  2. Mucha S, Melen-Mucha G, Stepien T, Godlewski A, Stepien H: Effects of pentosan polysulfate sodium on the estrogen-induced pituitary prolactinoma in Fischer 344 rats. Oncol Rep. 2002 Nov-Dec;9(6):1385-9. [PubMed:12375053]
  3. Pluda JM, Shay LE, Foli A, Tannenbaum S, Cohen PJ, Goldspiel BR, Adamo D, Cooper MR, Broder S, Yarchoan R: Administration of pentosan polysulfate to patients with human immunodeficiency virus-associated Kaposi's sarcoma. J Natl Cancer Inst. 1993 Oct 6;85(19):1585-92. [PubMed:7692072]
  4. McLeskey SW, Zhang L, Kharbanda S, Kurebayashi J, Lippman ME, Dickson RB, Kern FG: Fibroblast growth factor overexpressing breast carcinoma cells as models of angiogenesis and metastasis. Breast Cancer Res Treat. 1996;39(1):103-17. [PubMed:8738610]
  5. Jerebtsova M, Wong E, Przygodzki R, Tang P, Ray PE: A novel role of fibroblast growth factor-2 and pentosan polysulfate in the pathogenesis of intestinal bleeding in mice. Am J Physiol Heart Circ Physiol. 2007 Feb;292(2):H743-50. Epub 2006 Oct 27. [PubMed:17071728]
Kind
Protein
Organism
Human
Pharmacological action
Yes
Actions
Antagonist
General Function
S100 protein binding
Specific Function
Plays an important role in the regulation of cell survival, cell division, angiogenesis, cell differentiation and cell migration. Functions as potent mitogen in vitro.
Gene Name
FGF1
Uniprot ID
P05230
Uniprot Name
Fibroblast growth factor 1
Molecular Weight
17459.58 Da
References
  1. Pascu C, Ljungh A, Wadstrom T: Staphylococci bind heparin-binding host growth factors. Curr Microbiol. 1996 Apr;32(4):201-7. [PubMed:8867461]
  2. Zenjari C, Boilly-Marer Y, Desbiens X, Oudghir M, Hondermarck H, Boilly B: Experimental evidence for FGF-1 control of blastema cell proliferation during limb regeneration of the amphibian Pleurodeles waltl. Int J Dev Biol. 1996 Oct;40(5):965-71. [PubMed:8946244]
  3. Jerebtsova M, Wong E, Przygodzki R, Tang P, Ray PE: A novel role of fibroblast growth factor-2 and pentosan polysulfate in the pathogenesis of intestinal bleeding in mice. Am J Physiol Heart Circ Physiol. 2007 Feb;292(2):H743-50. Epub 2006 Oct 27. [PubMed:17071728]
Kind
Protein
Organism
Human
Pharmacological action
Unknown
Actions
Inhibitor
General Function
Heparin binding
Specific Function
Plays an important role in the regulation of embryonic development, cell proliferation, and cell differentiation. Required for normal limb and cardiac valve development during embryogenesis.
Gene Name
FGF4
Uniprot ID
P08620
Uniprot Name
Fibroblast growth factor 4
Molecular Weight
22047.355 Da
References
  1. Zugmaier G, Lippman ME, Wellstein A: Inhibition by pentosan polysulfate (PPS) of heparin-binding growth factors released from tumor cells and blockage by PPS of tumor growth in animals. J Natl Cancer Inst. 1992 Nov 18;84(22):1716-24. [PubMed:1279186]
  2. McLeskey SW, Zhang L, Kharbanda S, Kurebayashi J, Lippman ME, Dickson RB, Kern FG: Fibroblast growth factor overexpressing breast carcinoma cells as models of angiogenesis and metastasis. Breast Cancer Res Treat. 1996;39(1):103-17. [PubMed:8738610]
  3. Wellstein A, Zugmaier G, Califano JA 3rd, Kern F, Paik S, Lippman ME: Tumor growth dependent on Kaposi's sarcoma-derived fibroblast growth factor inhibited by pentosan polysulfate. J Natl Cancer Inst. 1991 May 15;83(10):716-20. [PubMed:1708834]

Drug created on June 13, 2005 07:24 / Updated on November 14, 2018 12:44