Identification

Name
Suramin
Accession Number
DB04786
Type
Small Molecule
Groups
Approved, Investigational
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
  • 8,8'-[CARBONYLBIS[imino-3,1-phenylenecarbonylimino(4-methyl-3,1-phenylene)carbonylimino]]bis-1,3,5-naphthalenetrisulfonic acid
  • Belganyl
  • Naganol
  • Naphuride
  • Suramin
  • Suramine
Product Ingredients
IngredientUNIICASInChI Key
Suramin sodium89521262IH129-46-4VAPNKLKDKUDFHK-UHFFFAOYSA-H
International/Other Brands
309 Fourneau / Antrypol / Bayer 205 / Belganyl / Germanin (Bayer) / Moranyl / Naganin / Naganine / Naganol / Naphuride
Categories
UNII
6032D45BEM
CAS number
145-63-1
Weight
Average: 1297.28
Monoisotopic: 1296.046905756
Chemical Formula
C51H40N6O23S6
InChI Key
FIAFUQMPZJWCLV-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)benzamido]benzamido}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

Pharmacology

Indication

For treatment of human sleeping sickness, onchocerciasis and other diseases caused by trypanosomes and worms.

Structured Indications
Not Available
Pharmacodynamics
Not Available
Mechanism of action

The 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.

TargetActionsOrganism
AP2Y purinoceptor 2
antagonist
Human
ANAD-dependent protein deacylase sirtuin-5, mitochondrial
inhibitor
Human
AFollicle-stimulating hormone receptor
antagonist
Human
URyanodine receptor 1
agonist
Human
UProthrombin
inhibitor
Human
UPhospholipase A2, membrane associated
inhibitor
Human
UComplement control protein C3Not AvailableVACV
Absorption

Poorly absorbed from the gastrointestinal tract.

Volume of distribution
Not Available
Protein binding

Approximately 99.7%

Metabolism

Little or no metabolism

Route of elimination
Not Available
Half life

Approximately 36 to 60 days

Clearance
Not Available
Toxicity
Not Available
Affected organisms
  • Yeast, Molds, Trypanosomes
Pathways
Not Available
Pharmacogenomic Effects/ADRs
Not Available

Interactions

Drug Interactions
DrugInteractionDrug group
AcetyldigitoxinAcetyldigitoxin may decrease the cardiotoxic activities of Suramin.Approved
AcetyldigoxinAcetyldigoxin may decrease the cardiotoxic activities of Suramin.Experimental
AmodiaquineThe serum concentration of Suramin can be decreased when it is combined with Amodiaquine.Approved, Investigational
BevacizumabBevacizumab may increase the cardiotoxic activities of Suramin.Approved, Investigational
CabazitaxelThe risk or severity of adverse effects can be increased when Cabazitaxel is combined with Suramin.Approved
ChloroquineThe serum concentration of Suramin can be decreased when it is combined with Chloroquine.Approved, Vet Approved
CyclophosphamideCyclophosphamide may increase the cardiotoxic activities of Suramin.Approved, Investigational
CymarinCymarin may decrease the cardiotoxic activities of Suramin.Experimental
DeslanosideDeslanoside may decrease the cardiotoxic activities of Suramin.Approved
DigitoxinDigitoxin may decrease the cardiotoxic activities of Suramin.Approved, Investigational
DigoxinDigoxin may decrease the cardiotoxic activities of Suramin.Approved
Digoxin Immune Fab (Ovine)Digoxin Immune Fab (Ovine) may decrease the cardiotoxic activities of Suramin.Approved
DocetaxelThe risk or severity of adverse effects can be increased when Docetaxel is combined with Suramin.Approved, Investigational
GitoformateGitoformate may decrease the cardiotoxic activities of Suramin.Experimental
HydroxychloroquineThe serum concentration of Suramin can be decreased when it is combined with Hydroxychloroquine.Approved
Lanatoside CLanatoside C may decrease the cardiotoxic activities of Suramin.Experimental
MetildigoxinMetildigoxin may decrease the cardiotoxic activities of Suramin.Experimental
OleandrinOleandrin may decrease the cardiotoxic activities of Suramin.Experimental, Investigational
OuabainOuabain may decrease the cardiotoxic activities of Suramin.Approved
PaclitaxelThe risk or severity of adverse effects can be increased when Paclitaxel is combined with Suramin.Approved, Vet Approved
PeruvosidePeruvoside may decrease the cardiotoxic activities of Suramin.Experimental
PrimaquineThe serum concentration of Suramin can be decreased when it is combined with Primaquine.Approved
ProscillaridinProscillaridin may decrease the cardiotoxic activities of Suramin.Experimental
TrastuzumabTrastuzumab may increase the cardiotoxic activities of Suramin.Approved, Investigational
Food Interactions
Not Available

References

General References
Not Available
External Links
Human Metabolome Database
HMDB15582
KEGG Compound
C07974
PubChem Compound
5361
PubChem Substance
46507013
ChemSpider
5168
BindingDB
50336799
ChEBI
45906
ChEMBL
CHEMBL265502
Therapeutic Targets Database
DAP001031
PharmGKB
PA10292
IUPHAR
1728
Guide to Pharmacology
GtP Drug Page
HET
SVR
Wikipedia
Suramin
ATC Codes
P01CX02 — Suramin sodium
PDB Entries
1y4l / 1y8e / 2h9t / 2nyr / 3bf6 / 3bjw / 3gan / 3pp7 / 3ur0 / 4j4v
show 2 more

Clinical Trials

Clinical Trials
PhaseStatusPurposeConditionsCount
1CompletedTreatmentAdrenocortical Carcinoma / Cancer, Breast / Colorectal Cancers / Prostate Cancer / Unspecified Adult Solid Tumor, Protocol Specific1
1CompletedTreatmentBladder Cancers1
1CompletedTreatmentNeoplasm, Bladder / Transitional Cell Carcinoma1
1CompletedTreatmentRecurrent Non-small Cell Lung Cancer / Stage IIIb Non-small Cell Lung Cancer / Stage IV Non-Small Cell Lung Cancer1
1, 2CompletedTreatmentAutism Spectrum Conditions/Disorders1
1, 2CompletedTreatmentRecurrent Breast Cancer / Stage IIIB Breast Cancer / Stage IV Breast Cancer1
1, 2CompletedTreatmentRenal Cell Carcinoma Recurrent / Stage IV Renal Cell Cancer1
2Active Not RecruitingTreatmentNon Small Cell Lung Carcinoma (NSCLC)1
2CompletedTreatmentBrain and Central Nervous System Tumors2
2CompletedTreatmentMultiple Myeloma and Plasma Cell Neoplasm1
2CompletedTreatmentProstatic Neoplasms1
2CompletedTreatmentRecurrent Non-small Cell Lung Cancer / Stage IIIb Non-small Cell Lung Cancer / Stage IV Non-Small Cell Lung Cancer1
2TerminatedTreatmentAdrenocortical Carcinoma1
2TerminatedTreatmentLung Cancer Non-Small Cell Cancer (NSCLC)1
3CompletedTreatmentProstate Cancer2

Pharmacoeconomics

Manufacturers
Not Available
Packagers
Not Available
Dosage forms
Not Available
Prices
Not Available
Patents
Not Available

Properties

State
Solid
Experimental Properties
Not Available
Predicted Properties
PropertyValueSource
Water Solubility0.00872 mg/mLALOGPS
logP-0.12ALOGPS
logP5.58ChemAxon
logS-5.2ALOGPS
pKa (Strongest Acidic)-3.5ChemAxon
Physiological Charge-6ChemAxon
Hydrogen Acceptor Count23ChemAxon
Hydrogen Donor Count12ChemAxon
Polar Surface Area483.75 Å2ChemAxon
Rotatable Bond Count16ChemAxon
Refractivity314.9 m3·mol-1ChemAxon
Polarizability120.22 Å3ChemAxon
Number of Rings8ChemAxon
Bioavailability0ChemAxon
Rule of FiveNoChemAxon
Ghose FilterNoChemAxon
Veber's RuleNoChemAxon
MDDR-like RuleYesChemAxon
Predicted ADMET features
PropertyValueProbability
Human Intestinal Absorption-0.7333
Blood Brain Barrier+0.8186
Caco-2 permeable-0.5901
P-glycoprotein substrateNon-substrate0.7739
P-glycoprotein inhibitor INon-inhibitor0.8805
P-glycoprotein inhibitor IINon-inhibitor0.8545
Renal organic cation transporterNon-inhibitor0.9383
CYP450 2C9 substrateNon-substrate0.5122
CYP450 2D6 substrateNon-substrate0.8142
CYP450 3A4 substrateNon-substrate0.6631
CYP450 1A2 substrateNon-inhibitor0.7894
CYP450 2C9 inhibitorNon-inhibitor0.8854
CYP450 2D6 inhibitorNon-inhibitor0.9264
CYP450 2C19 inhibitorNon-inhibitor0.8912
CYP450 3A4 inhibitorNon-inhibitor0.9572
CYP450 inhibitory promiscuityLow CYP Inhibitory Promiscuity0.924
Ames testNon AMES toxic0.7113
CarcinogenicityCarcinogens 0.7574
BiodegradationNot ready biodegradable0.9699
Rat acute toxicity2.1516 LD50, mol/kg Not applicable
hERG inhibition (predictor I)Weak inhibitor0.9836
hERG inhibition (predictor II)Non-inhibitor0.8448
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 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 benzanilides. These are aromatic compounds containing an anilide group in which the carboxamide group is substituted with a benzene ring. They have the general structure RNC(=O)R', where R,R'= benzene.
Kingdom
Organic compounds
Super Class
Benzenoids
Class
Benzene and substituted derivatives
Sub Class
Anilides
Direct Parent
Benzanilides
Alternative Parents
1-naphthalene sulfonates / 1-naphthalene sulfonic acids and derivatives / 2-naphthalene sulfonates / 2-naphthalene sulfonic acids and derivatives / N-phenylureas / p-Toluamides / Benzamides / 1-sulfo,2-unsubstituted aromatic compounds / Benzoyl derivatives / Sulfonyls
show 8 more
Substituents
Benzanilide / Naphthalene sulfonate / 1-naphthalene sulfonic acid or derivatives / 2-naphthalene sulfonic acid or derivatives / Naphthalene sulfonic acid or derivatives / 1-naphthalene sulfonate / 2-naphthalene sulfonate / N-phenylurea / Naphthalene / P-toluamide
show 26 more
Molecular Framework
Aromatic homopolycyclic compounds
External Descriptors
naphthalenesulfonic acid (CHEBI:45906)

Targets

Details
1. P2Y purinoceptor 2
Kind
Protein
Organism
Human
Pharmacological action
Yes
Actions
Antagonist
General Function
Utp-activated nucleotide receptor activity
Specific Function
Receptor for ATP and UTP coupled to G-proteins that activate a phosphatidylinositol-calcium second messenger system. The affinity range is UTP = ATP > ATP-gamma-S >> 2-methylthio-ATP = ADP.
Gene Name
P2RY2
Uniprot ID
P41231
Uniprot Name
P2Y purinoceptor 2
Molecular Weight
42272.92 Da
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:8762097]
  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:9647463]
  3. Trujillo CA, Nery AA, Martins AH, Majumder P, Gonzalez FA, Ulrich H: Inhibition mechanism of the recombinant rat P2X(2) receptor in glial cells by suramin and TNP-ATP. Biochemistry. 2006 Jan 10;45(1):224-33. [PubMed:16388598]
  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:9112981]
  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:11132624]
Kind
Protein
Organism
Human
Pharmacological action
Yes
Actions
Inhibitor
General Function
Zinc ion binding
Specific Function
NAD-dependent lysine demalonylase, desuccinylase and deglutarylase that specifically removes malonyl, succinyl and glutaryl groups on target proteins (PubMed:21908771, PubMed:22076378, PubMed:24703...
Gene Name
SIRT5
Uniprot ID
Q9NXA8
Uniprot Name
NAD-dependent protein deacylase sirtuin-5, mitochondrial
Molecular Weight
33880.605 Da
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:17355872]
Kind
Protein
Organism
Human
Pharmacological action
Yes
Actions
Antagonist
General Function
G-protein coupled peptide receptor activity
Specific Function
Receptor for follicle-stimulating hormone. The activity of this receptor is mediated by G proteins which activate adenylate cyclase. Induces cAMP production through the activation of PI3K-AKT and S...
Gene Name
FSHR
Uniprot ID
P23945
Uniprot Name
Follicle-stimulating hormone receptor
Molecular Weight
78264.07 Da
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:18991754]
  2. Bose CK: Follicle stimulating hormone receptor (FSHR) antagonist and epithelial ovarian cancer (EOC). J Exp Ther Oncol. 2007;6(3):201-4. [PubMed:17552360]
Kind
Protein
Organism
Human
Pharmacological action
Unknown
Actions
Agonist
General Function
Voltage-gated calcium channel activity
Specific Function
Calcium channel that mediates the release of Ca(2+) from the sarcoplasmic reticulum into the cytoplasm and thereby plays a key role in triggering muscle contraction following depolarization of T-tu...
Gene Name
RYR1
Uniprot ID
P21817
Uniprot Name
Ryanodine receptor 1
Molecular Weight
565170.715 Da
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:16056233]
Kind
Protein
Organism
Human
Pharmacological action
Unknown
Actions
Inhibitor
General Function
Thrombospondin receptor activity
Specific Function
Thrombin, which cleaves bonds after Arg and Lys, converts fibrinogen to fibrin and activates factors V, VII, VIII, XIII, and, in complex with thrombomodulin, protein C. Functions in blood homeostas...
Gene Name
F2
Uniprot ID
P00734
Uniprot Name
Prothrombin
Molecular Weight
70036.295 Da
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:15203120]
Kind
Protein
Organism
Human
Pharmacological action
Unknown
Actions
Inhibitor
General Function
Phospholipid binding
Specific Function
Thought to participate in the regulation of the phospholipid metabolism in biomembranes including eicosanoid biosynthesis. Catalyzes the calcium-dependent hydrolysis of the 2-acyl groups in 3-sn-ph...
Gene Name
PLA2G2A
Uniprot ID
P14555
Uniprot Name
Phospholipase A2, membrane associated
Molecular Weight
16082.525 Da
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:15961104]
  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:10592235]
Kind
Protein
Organism
VACV
Pharmacological action
Unknown
General Function
Not Available
Specific Function
Serves to protect the virus against complement attack by inhibiting both classical and alternative pathways of complement activation. Binds C3b and C4b.
Gene Name
Not Available
Uniprot ID
P68638
Uniprot Name
Complement control protein C3
Molecular Weight
28629.03 Da
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:16086578]

Enzymes

Kind
Protein
Organism
Human
Pharmacological action
Unknown
Actions
Inhibitor
General Function
Sulfuric ester hydrolase activity
Specific Function
Hydrolyzes cerebroside sulfate.
Gene Name
ARSA
Uniprot ID
P15289
Uniprot Name
Arylsulfatase A
Molecular Weight
53587.6 Da
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:7291729]
Kind
Protein
Organism
Human
Pharmacological action
Unknown
Actions
Inhibitor
General Function
Phospholipase a2 activity
Specific Function
Selectively hydrolyzes arachidonyl phospholipids in the sn-2 position releasing arachidonic acid. Together with its lysophospholipid activity, it is implicated in the initiation of the inflammatory...
Gene Name
PLA2G4A
Uniprot ID
P47712
Uniprot Name
Cytosolic phospholipase A2
Molecular Weight
85238.2 Da
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. doi: 10.1016/j.bioorg.2009.01.002. Epub 2009 Feb 3. [PubMed:19251299]
  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. doi: 10.1007/s00011-008-8137-z. [PubMed:19169647]

Drug created on September 11, 2007 11:49 / Updated on November 09, 2017 03:47