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Identification
NameSodium stibogluconate
Accession NumberDB05630
TypeSmall Molecule
GroupsApproved, Investigational
Description

Sodium stibogluconate is a medicine used to treat leishmaniasis and is only available for administration by injection. It belongs to the class of medicines known as the pentavalent antimonials. Sodium stibogluconate is sold in the UK as Pentostam (manufactured by GlaxoSmithKline). Widespread resistance has limited the utility of sodium stibogluconate, and in many parts of the world, amphotericin or miltefosine are used instead. It is also being investigated as an anti-tumor agent.

Structure
Thumb
Synonyms
Antimony (v) derivative OF sodium gluconate
Antimony sodium gluconate
Estibogluconato sodico
Myostibin
Natrii stibogluconas
Pentostam
Sodium stibogluconate
Stibanate
Stibanose
Stibatin
Stibinol
Stibogluconate de sodium
Trisodium 1-{[3-carboxylato-5-(1,2-dihydroxyethyl)-1-hydroxy-2,6,7-trioxa-1lambda(5)-stibabicyclo[2.2.1]hept-1-yl]oxy}-5-(1,2-dihydroxyethyl)-1-oxido-2,6,7-trioxa-1lambda(5)-stibabicyclo[2.2.1]heptane-3-carboxylate nonahydrate
External Identifiers Not Available
Approved Prescription ProductsNot Available
Approved Generic Prescription ProductsNot Available
Approved Over the Counter ProductsNot Available
Unapproved/Other Products Not Available
International Brands
NameCompany
PentostamGlaxoSmithKline
Brand mixturesNot Available
SaltsNot Available
Categories
UNIIAPJ6285Y89
CAS number16037-91-5
WeightAverage: 907.88
Monoisotopic: 905.918601405
Chemical FormulaC12H35Na3O26Sb2
InChI KeyInChIKey=YQDGWZZYGYKDLR-UZVLBLASSA-K
InChI
InChI=1S/2C6H9O7.3Na.10H2O.2O.2Sb/c2*7-1-2(8)3(9)4(10)5(11)6(12)13;;;;;;;;;;;;;;;;;/h2*2-5,7-8H,1H2,(H,12,13);;;;10*1H2;;;;/q2*-3;3*+1;;;;;;;;;;;;-1;+3;+4/p-3/t2*2-,3-,4+,5-;;;;;;;;;;;;;;;;;/m11................./s1
IUPAC Name
trisodium (3R,4S,5R)-1-{[(3R,4S,5R)-3-carboxylato-5-[(1R)-1,2-dihydroxyethyl]-1-oxido-2,6,7-trioxa-1-stibabicyclo[2.2.1]heptan-1-yl]oxy}-5-[(1R)-1,2-dihydroxyethyl]-1-hydroxy-2,6,7-trioxa-1-stibabicyclo[2.2.1]heptane-3-carboxylate nonahydrate
SMILES
O.O.O.O.O.O.O.O.O.[Na+].[Na+].[Na+].[H][C@@]1(O[Sb]2(O)(O[Sb]34([O-])O[C@@H](C([O-])=O)[C@@]([H])(O3)[C@]([H])(O4)[[email protected]](O)CO)O[C@@H](C([O-])=O)[C@@]1([H])O2)[[email protected]](O)CO
Taxonomy
ClassificationNot classified
Pharmacology
IndicationFor the treatment of various types of a protozoal infection called leishmaniasis, which may result from sandfly bites in tropical and temperate parts of the world. Also investigated for use/treatment in cancer/tumors (unspecified) and solid tumors.
PharmacodynamicsThe mode of action of sodium stibogluconate is not clearly understood. In vitro exposure of amastigotes to 500 mg pentavalent antimony/ml results in a greater than 50% decrease in parasite DNA, RNA protein and purine nucleoside triphosphate levels. It has been postulated that the reduction in ATP (adenosine triphosphate) and GTP (guanosine triphosphate) synthesis contributes to decreased macromolecular synthesis.
Mechanism of actionSodium stibogluconate directly inhibits DNA topoisomerase I leading to inhibition of both DNA replication and transcription.
Related Articles
AbsorptionNot Available
Volume of distributionNot Available
Protein bindingNot Available
MetabolismNot Available
Route of eliminationNot Available
Half lifeNot Available
ClearanceNot Available
ToxicityThe main symptoms of antimony overdosage are gastro-intestinal disturbances (nausea, vomiting and severe diarrhoea). Haemorrhagic nephritis and hepatitis may also occur.
Affected organisms
  • Humans and other mammals
  • Protozoa
PathwaysNot Available
SNP Mediated EffectsNot Available
SNP Mediated Adverse Drug ReactionsNot Available
ADMET
Predicted ADMET features
PropertyValueProbability
Human Intestinal Absorption-0.9877
Blood Brain Barrier+0.7918
Caco-2 permeable-0.6847
P-glycoprotein substrateNon-substrate0.5879
P-glycoprotein inhibitor INon-inhibitor0.7637
P-glycoprotein inhibitor IINon-inhibitor0.9641
Renal organic cation transporterNon-inhibitor0.8876
CYP450 2C9 substrateNon-substrate0.8656
CYP450 2D6 substrateNon-substrate0.8282
CYP450 3A4 substrateNon-substrate0.5946
CYP450 1A2 substrateNon-inhibitor0.8279
CYP450 2C9 inhibitorNon-inhibitor0.8578
CYP450 2D6 inhibitorNon-inhibitor0.8796
CYP450 2C19 inhibitorNon-inhibitor0.79
CYP450 3A4 inhibitorNon-inhibitor0.937
CYP450 inhibitory promiscuityLow CYP Inhibitory Promiscuity0.9436
Ames testNon AMES toxic0.72
CarcinogenicityNon-carcinogens0.8598
BiodegradationNot ready biodegradable0.5984
Rat acute toxicity2.4267 LD50, mol/kg Not applicable
hERG inhibition (predictor I)Weak inhibitor0.8894
hERG inhibition (predictor II)Non-inhibitor0.7668
ADMET data is predicted using admetSAR, a free tool for evaluating chemical ADMET properties. (23092397 )
Pharmacoeconomics
ManufacturersNot Available
PackagersNot Available
Dosage formsNot Available
PricesNot Available
PatentsNot Available
Properties
StateSolid
Experimental PropertiesNot Available
Predicted Properties
PropertyValueSource
logP-3.4ChemAxon
pKa (Strongest Acidic)2.29ChemAxon
pKa (Strongest Basic)-3ChemAxon
Physiological Charge-2ChemAxon
Hydrogen Acceptor Count17ChemAxon
Hydrogen Donor Count5ChemAxon
Polar Surface Area269.08 Å2ChemAxon
Rotatable Bond Count8ChemAxon
Refractivity96.29 m3·mol-1ChemAxon
Polarizability39.78 Å3ChemAxon
Number of Rings4ChemAxon
Bioavailability0ChemAxon
Rule of FiveYesChemAxon
Ghose FilterYesChemAxon
Veber's RuleYesChemAxon
MDDR-like RuleYesChemAxon
Spectra
Mass Spec (NIST)Not Available
SpectraNot Available
References
Synthesis ReferenceNot Available
General References
  1. Murray HW, Berman JD, Davies CR, Saravia NG: Advances in leishmaniasis. Lancet. 2005 Oct 29-Nov 4;366(9496):1561-77. [PubMed:16257344 ]
External Links
ATC CodesP01CB02
AHFS CodesNot Available
PDB EntriesNot Available
FDA labelNot Available
MSDSNot Available
Interactions
Drug InteractionsNot Available
Food InteractionsNot Available

Targets

Kind
Protein
Organism
Human
Pharmacological action
yes
Actions
inhibitor
General Function:
Poly(a) rna binding
Specific Function:
Releases the supercoiling and torsional tension of DNA introduced during the DNA replication and transcription by transiently cleaving and rejoining one strand of the DNA duplex. Introduces a single-strand break via transesterification at a target site in duplex DNA. The scissile phosphodiester is attacked by the catalytic tyrosine of the enzyme, resulting in the formation of a DNA-(3'-phosphot...
Gene Name:
TOP1
Uniprot ID:
P11387
Molecular Weight:
90725.19 Da
References
  1. Walker J, Saravia NG: Inhibition of Leishmania donovani promastigote DNA topoisomerase I and human monocyte DNA topoisomerases I and II by antimonial drugs and classical antitopoisomerase agents. J Parasitol. 2004 Oct;90(5):1155-62. [PubMed:15562618 ]
  2. Chakraborty AK, Majumder HK: Mode of action of pentavalent antimonials: specific inhibition of type I DNA topoisomerase of Leishmania donovani. Biochem Biophys Res Commun. 1988 Apr 29;152(2):605-11. [PubMed:2835038 ]
  3. 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 ]
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Drug created on November 18, 2007 11:26 / Updated on September 16, 2013 17:27