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Identification
NameSuramin
Accession NumberDB04786
Typesmall molecule
Groupsapproved
Description

A polyanionic compound with an unknown mechanism of action. It is used parenterally in the treatment of African trypanosomiasis and it has been used clinically with diethylcarbamazine to kill the adult Onchocerca. (From AMA Drug Evaluations Annual, 1992, p1643) It has also been shown to have potent antineoplastic properties. Suramin is manufactured by Bayer in Germany as Germanin®.

Structure
Thumb
Synonyms
SynonymLanguageCode
8,8'-[CARBONYLBIS[imino-3,1-phenylenecarbonylimino(4-methyl-3,1-phenylene)carbonylimino]]bis-1,3,5-naphthalenetrisulfonic acidNot AvailableNot Available
BelganylNot AvailableNot Available
NaganolNot AvailableNot Available
NaphurideNot AvailableNot Available
SuraminNot AvailableNot Available
SuramineNot AvailableNot Available
Salts
Name/CAS Structure Properties
Suramin sodium
129-46-4
Thumb
  • InChI Key: VAPNKLKDKUDFHK-UHFFFAOYSA-H
  • Monoisotopic Mass: 1427.938573614
  • Average Mass: 1429.171
DBSALT000540
Brand names
NameCompany
309 FourneauNot Available
AntrypolNot Available
Bayer 205Not Available
BelganylNot Available
GermaninBayer
MoranylNot Available
NaganinNot Available
NaganineNot Available
NaganolNot Available
NaphurideNot Available
Brand mixturesNot Available
Categories
CAS number145-63-1
WeightAverage: 1297.28
Monoisotopic: 1296.046905756
Chemical FormulaC51H40N6O23S6
InChI KeyFIAFUQMPZJWCLV-UHFFFAOYSA-N
InChI
InChI=1S/C51H40N6O23S6/c1-25-9-11-29(49(60)54-37-13-15-41(83(69,70)71)35-21-33(81(63,64)65)23-43(45(35)37)85(75,76)77)19-39(25)56-47(58)27-5-3-7-31(17-27)52-51(62)53-32-8-4-6-28(18-32)48(59)57-40-20-30(12-10-26(40)2)50(61)55-38-14-16-42(84(72,73)74)36-22-34(82(66,67)68)24-44(46(36)38)86(78,79)80/h3-24H,1-2H3,(H,54,60)(H,55,61)(H,56,58)(H,57,59)(H2,52,53,62)(H,63,64,65)(H,66,67,68)(H,69,70,71)(H,72,73,74)(H,75,76,77)(H,78,79,80)
IUPAC Name
8-[(4-methyl-3-{[3-({[3-({2-methyl-5-[(4,6,8-trisulfonaphthalen-1-yl)carbamoyl]phenyl}carbamoyl)phenyl]carbamoyl}amino)benzene]amido}benzene)amido]naphthalene-1,3,5-trisulfonic acid
SMILES
CC1=C(NC(=O)C2=CC(NC(=O)NC3=CC=CC(=C3)C(=O)NC3=C(C)C=CC(=C3)C(=O)NC3=C4C(C=C(C=C4S(O)(=O)=O)S(O)(=O)=O)=C(C=C3)S(O)(=O)=O)=CC=C2)C=C(C=C1)C(=O)NC1=C2C(C=C(C=C2S(O)(=O)=O)S(O)(=O)=O)=C(C=C1)S(O)(=O)=O
Mass SpecNot Available
Taxonomy
KingdomOrganic Compounds
SuperclassBenzenoids
ClassBenzene and Substituted Derivatives
SubclassBenzamides
Direct parentN-phenylbenzamides
Alternative parentsNaphthalenes; Anilides; Aminobenzamides; Benzoyl Derivatives; Toluenes; Organic Sulfites; Sulfonyls; Sulfonic Acids; Secondary Carboxylic Acid Amides; Carboxylic Acids; Enolates; Polyamines
Substituentsacene; naphthalene; acetanilide; aminobenzamide; benzoyl; toluene; sulfonic acid derivative; sulfonic acid; sulfonyl; organic sulfite; secondary carboxylic acid amide; carboxamide group; polyamine; carboxylic acid derivative; carboxylic acid; enolate; amine; organonitrogen compound
Classification descriptionThis compound belongs to the n-phenylbenzamides.
Pharmacology
IndicationFor treatment of human sleeping sickness, onchocerciasis and other diseases caused by trypanosomes and worms.
PharmacodynamicsNot Available
Mechanism of actionThe mechanism is unknown, but the trypanocidal activity may be due to the inhibition of enzymes involved with the oxidation of reduced nicotinamide-adenine dinucleotide (NADH), which functions as a co-enzyme in many cellular reactions, such as respiration and glycolysis, in the trypanosome parasite. Suramin's action in the treatment of onchocerciasis is macrofilaricidal and partially microfilaricidal. It may also act as an antagonist of P2 receptors and as an agonist of Ryanodine receptors. It also can inhibit follicle-stimulating hormone receptors.
AbsorptionPoorly absorbed from the gastrointestinal tract.
Volume of distributionNot Available
Protein bindingApproximately 99.7%
Metabolism

Little or no metabolism

Route of eliminationNot Available
Half lifeApproximately 36 to 60 days
ClearanceNot Available
ToxicityNot Available
Affected organisms
  • Yeast, Molds, Trypanosomes
PathwaysNot Available
SNP Mediated EffectsNot Available
SNP Mediated Adverse Drug ReactionsNot Available
ADMET
Predicted ADMET features
Property Value Probability
Human Intestinal Absorption - 0.7333
Blood Brain Barrier + 0.8186
Caco-2 permeable - 0.5901
P-glycoprotein substrate Non-substrate 0.7739
P-glycoprotein inhibitor I Non-inhibitor 0.8805
P-glycoprotein inhibitor II Non-inhibitor 0.8545
Renal organic cation transporter Non-inhibitor 0.9383
CYP450 2C9 substrate Non-substrate 0.5122
CYP450 2D6 substrate Non-substrate 0.8142
CYP450 3A4 substrate Non-substrate 0.6631
CYP450 1A2 substrate Non-inhibitor 0.7894
CYP450 2C9 substrate Non-inhibitor 0.8854
CYP450 2D6 substrate Non-inhibitor 0.9264
CYP450 2C19 substrate Non-inhibitor 0.8912
CYP450 3A4 substrate Non-inhibitor 0.9572
CYP450 inhibitory promiscuity Low CYP Inhibitory Promiscuity 0.924
Ames test Non AMES toxic 0.7113
Carcinogenicity Carcinogens 0.7574
Biodegradation Not ready biodegradable 0.9699
Rat acute toxicity 2.1516 LD50, mol/kg Not applicable
hERG inhibition (predictor I) Weak inhibitor 0.9836
hERG inhibition (predictor II) Non-inhibitor 0.8448
Pharmacoeconomics
ManufacturersNot Available
PackagersNot Available
Dosage forms
FormRouteStrength
Injection, powder, for solutionIntravenous
PricesNot Available
PatentsNot Available
Properties
Statesolid
Experimental PropertiesNot Available
Predicted Properties
PropertyValueSource
water solubility8.72e-03 g/lALOGPS
logP-0.12ALOGPS
logP5.58ChemAxon
logS-5.2ALOGPS
pKa (strongest acidic)-3.5ChemAxon
physiological charge-6ChemAxon
hydrogen acceptor count23ChemAxon
hydrogen donor count12ChemAxon
polar surface area483.75ChemAxon
rotatable bond count16ChemAxon
refractivity314.9ChemAxon
polarizability120.22ChemAxon
number of rings8ChemAxon
bioavailability0ChemAxon
rule of fiveNoChemAxon
Ghose filterNoChemAxon
Veber's ruleNoChemAxon
MDDR-like ruleYesChemAxon
Spectra
SpectraNot Available
References
Synthesis ReferenceNot Available
General ReferenceNot Available
External Links
ResourceLink
KEGG CompoundC07974
PubChem Compound5361
PubChem Substance46507013
ChemSpider5168
ChEBI45906
ChEMBLCHEMBL265502
Therapeutic Targets DatabaseDAP001031
PharmGKBPA10292
IUPHAR1728
Guide to Pharmacology1728
HETSVR
WikipediaSuramin
ATC CodesP01CX02
AHFS CodesNot Available
PDB EntriesNot Available
FDA labelNot Available
MSDSNot Available
Interactions
Drug InteractionsNot Available
Food InteractionsNot Available

Targets

1. P2Y purinoceptor 2

Kind: protein

Organism: Human

Pharmacological action: yes

Actions: antagonist

Components

Name UniProt ID Details
P2Y purinoceptor 2 P41231 Details

References:

  1. Charlton SJ, Brown CA, Weisman GA, Turner JT, Erb L, Boarder MR: PPADS and suramin as antagonists at cloned P2Y- and P2U-purinoceptors. Br J Pharmacol. 1996 Jun;118(3):704-10. Pubmed
  2. Bogdanov YD, Wildman SS, Clements MP, King BF, Burnstock G: Molecular cloning and characterization of rat P2Y4 nucleotide receptor. Br J Pharmacol. 1998 Jun;124(3):428-30. Pubmed
  3. Trujillo CA, Nery AA, Martins AH, Majumder P, Gonzalez FA, Ulrich H: Inhibition mechanism of the recombinant rat P2X receptor in glial cells by suramin and TNP-ATP. Biochemistry. 2006 Jan 10;45(1):224-33. Pubmed
  4. Churchill GC, Louis CF: Stimulation of P2U purinergic or alpha 1A adrenergic receptors mobilizes Ca2+ in lens cells. Invest Ophthalmol Vis Sci. 1997 Apr;38(5):855-65. Pubmed
  5. Homma R, Kimoto T, Niimura Y, Krivosheev A, Hara T, Ohta Y, Kawato S: Real-time fluorescence analysis on molecular mechanisms for regulation of cytochrome P450scc activity upon steroidogenic stimulation in adrenocortical cells. J Inorg Biochem. 2000 Nov;82(1-4):171-80. Pubmed

2. NAD-dependent protein deacylase sirtuin-5, mitochondrial

Kind: protein

Organism: Human

Pharmacological action: yes

Actions: inhibitor

Components

Name UniProt ID Details
NAD-dependent protein deacylase sirtuin-5, mitochondrial Q9NXA8 Details

References:

  1. Schuetz A, Min J, Antoshenko T, Wang CL, Allali-Hassani A, Dong A, Loppnau P, Vedadi M, Bochkarev A, Sternglanz R, Plotnikov AN: Structural basis of inhibition of the human NAD+-dependent deacetylase SIRT5 by suramin. Structure. 2007 Mar;15(3):377-89. Pubmed

3. Follicle-stimulating hormone receptor

Kind: protein

Organism: Human

Pharmacological action: yes

Actions: antagonist

Components

Name UniProt ID Details
Follicle-stimulating hormone receptor P23945 Details

References:

  1. McGeary RP, Bennett AJ, Tran QB, Cosgrove KL, Ross BP: Suramin: clinical uses and structure-activity relationships. Mini Rev Med Chem. 2008 Nov;8(13):1384-94. Pubmed
  2. Bose CK: Follicle stimulating hormone receptor (FSHR) antagonist and epithelial ovarian cancer (EOC). J Exp Ther Oncol. 2007;6(3):201-4. Pubmed

4. Ryanodine receptor 1

Kind: protein

Organism: Human

Pharmacological action: unknown

Actions: agonist

Components

Name UniProt ID Details
Ryanodine receptor 1 P21817 Details

References:

  1. Wolner I, Kassack MU, Ullmann H, Karel A, Hohenegger M: Use-dependent inhibition of the skeletal muscle ryanodine receptor by the suramin analogue NF676. Br J Pharmacol. 2005 Oct;146(4):525-33. Pubmed

5. Prothrombin

Kind: protein

Organism: Human

Pharmacological action: unknown

Actions: inhibitor

Components

Name UniProt ID Details
Prothrombin P00734 Details

References:

  1. Monteiro RQ, Campana PT, Melo PA, Bianconi ML: Suramin interaction with human alpha-thrombin: inhibitory effects and binding studies. Int J Biochem Cell Biol. 2004 Oct;36(10):2077-85. Pubmed

6. Phospholipase A2, membrane associated

Kind: protein

Organism: Human

Pharmacological action: unknown

Actions: inhibitor

Components

Name UniProt ID Details
Phospholipase A2, membrane associated P14555 Details

References:

  1. Murakami MT, Arruda EZ, Melo PA, Martinez AB, Calil-Elias S, Tomaz MA, Lomonte B, Gutierrez JM, Arni RK: Inhibition of myotoxic activity of Bothrops asper myotoxin II by the anti-trypanosomal drug suramin. J Mol Biol. 2005 Jul 15;350(3):416-26. Pubmed
  2. 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

7. Complement control protein C3

Kind: protein

Organism: VACV

Pharmacological action: unknown

Components

Name UniProt ID Details
Complement control protein C3 P68638 Details

References:

  1. Ganesh VK, Muthuvel SK, Smith SA, Kotwal GJ, Murthy KH: Structural basis for antagonism by suramin of heparin binding to vaccinia complement protein. Biochemistry. 2005 Aug 16;44(32):10757-65. Pubmed

Enzymes

1. Arylsulfatase A

Kind: protein

Organism: Human

Pharmacological action: unknown

Actions: inhibitor

Components

Name UniProt ID Details
Arylsulfatase A P15289 Details

References:

  1. Constantopoulos G, Rees S, Cragg BG, Barranger JA, Brady RO: Effect of suramin on the activities of degradative enzymes of sphingolipids in rats. Res Commun Chem Pathol Pharmacol. 1981 Apr;32(1):87-97. Pubmed

2. Cytosolic phospholipase A2

Kind: protein

Organism: Human

Pharmacological action: unknown

Actions: inhibitor

Components

Name UniProt ID Details
Cytosolic phospholipase A2 P47712 Details

References:

  1. Vieira DS, Aragao EA, Lourenzoni MR, Ward RJ: Mapping of suramin binding sites on the group IIA human secreted phospholipase A2. Bioorg Chem. 2009 Apr;37(2):41-5. Epub 2009 Feb 3. Pubmed]
  2. Aragao EA, Chioato L, Ferreira TL, de Medeiros AI, Secatto A, Faccioli LH, Ward RJ: Suramin inhibits macrophage activation by human group IIA phospholipase A2, but does not affect bactericidal activity of the enzyme. Inflamm Res. 2009 Apr;58(4):210-7. Pubmed

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Drug created on September 11, 2007 11:49 / Updated on September 16, 2013 17:25