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Record Information
Version2.0
Creation Date2009-07-21 20:26:53 UTC
Update Date2014-12-24 20:25:51 UTC
Accession NumberT3D2788
Identification
Common NameStreptozocin
ClassSmall Molecule
DescriptionStreptozocin is only found in individuals that have used or taken this drug.It is an antibiotic that is produced by Stretomyces achromogenes. It is used as an antineoplastic agent and to induce diabetes in experimental animals. [PubChem]Although its mechanism of action is not completely clear, streptozocin is known to inhibit DNA synthesis, interfere with biochemical reactions of NAD and NADH, and inhibit some enzymes involved in gluconeogenesis. Its activity appears to occur as a result of formation of methylcarbonium ions, which alkylate or bind with many intracellular molecular structures including nucleic acids. Its cytotoxic action is probably due to cross-linking of strands of DNA, resulting in inhibition of DNA synthesis.
Compound Type
  • Amine
  • Antibiotic
  • Antibiotic, Antineoplastic
  • Antineoplastic Agent
  • Drug
  • Metabolite
  • Organic Compound
  • Synthetic Compound
Chemical Structure
Thumb
Synonyms
Synonym
2-Deoxy-2-(((methylnitrosoamino)carbonyl)amino)-D-glucopyranose
2-Deoxy-2-(3-methyl-3-nitrosoureido)-D-glucopyranose
Estreptozocina
N-D-Glucosyl-(2)-n'-nitrosomethylharnstoff
N-D-Glucosyl-(2)-n'-nitrosomethylurea
Streptozocine
Streptozocinium
Streptozocinum
Streptozotocin
Zanosar
Chemical FormulaC8H15N3O7
Average Molecular Mass265.221 g/mol
Monoisotopic Mass265.091 g/mol
CAS Registry Number18883-66-4
IUPAC Name3-methyl-3-nitroso-1-[(2S,3R,4R,5S,6R)-2,4,5-trihydroxy-6-(hydroxymethyl)oxan-3-yl]urea
Traditional Namestreptozocin
SMILES[H][C@]1(O)O[C@]([H])(CO)[C@@]([H])(O)[C@]([H])(O)[C@@]1([H])N=C(O)N(C)N=O
InChI IdentifierInChI=1S/C8H15N3O7/c1-11(10-17)8(16)9-4-6(14)5(13)3(2-12)18-7(4)15/h3-7,12-15H,2H2,1H3,(H,9,16)/t3-,4-,5-,6-,7+/m1/s1
InChI KeyInChIKey=ZSJLQEPLLKMAKR-GKHCUFPYSA-N
Chemical Taxonomy
Description belongs to the class of organic compounds known as hexoses. These are monosaccharides in which the sugar unit is a is a six-carbon containing moeity.
KingdomOrganic compounds
Super ClassOrganic oxygen compounds
ClassOrganooxygen compounds
Sub ClassCarbohydrates and carbohydrate conjugates
Direct ParentHexoses
Alternative Parents
Substituents
  • Hexose monosaccharide
  • N-methylnitrosourea
  • Nitrosourea
  • Oxane
  • Nitrosamide
  • Semicarbazide
  • Organic n-nitroso compound
  • Hemiacetal
  • Carbonic acid derivative
  • Secondary alcohol
  • Organic nitroso compound
  • Oxacycle
  • Polyol
  • Organoheterocyclic compound
  • Organonitrogen compound
  • Hydrocarbon derivative
  • Organic oxide
  • Organopnictogen compound
  • Organic nitrogen compound
  • Carbonyl group
  • Primary alcohol
  • Alcohol
  • Aliphatic heteromonocyclic compound
Molecular FrameworkAliphatic heteromonocyclic compounds
External Descriptors
Biological Properties
StatusDetected and Not Quantified
OriginExogenous
Cellular Locations
  • Cytoplasm
  • Extracellular
  • Membrane
Biofluid LocationsNot Available
Tissue LocationsNot Available
PathwaysNot Available
Applications
Biological Roles
Chemical Roles
Physical Properties
StateSolid
AppearanceWhite powder.
Experimental Properties
PropertyValue
Melting Point115°C
Boiling PointNot Available
Solubility5070 mg/L
LogP-1.45
Predicted Properties
PropertyValueSource
Water Solubility33.5 g/LALOGPS
logP-1.7ALOGPS
logP-2.7ChemAxon
logS-0.9ALOGPS
pKa (Strongest Acidic)11.43ChemAxon
pKa (Strongest Basic)-3ChemAxon
Physiological Charge0ChemAxon
Hydrogen Acceptor Count7ChemAxon
Hydrogen Donor Count5ChemAxon
Polar Surface Area151.92 ŲChemAxon
Rotatable Bond Count3ChemAxon
Refractivity55.96 m³·mol⁻¹ChemAxon
Polarizability23.74 ųChemAxon
Number of Rings1ChemAxon
Bioavailability1ChemAxon
Rule of FiveYesChemAxon
Ghose FilterYesChemAxon
Veber's RuleYesChemAxon
MDDR-like RuleYesChemAxon
Spectra
Spectra
Spectrum TypeDescriptionSplash KeyView
Predicted GC-MSPredicted GC-MS Spectrum - GC-MS (Non-derivatized) - 70eV, Positivesplash10-02mj-5940000000-8fb8f1885498bea8bc01JSpectraViewer
Predicted GC-MSPredicted GC-MS Spectrum - GC-MS (4 TMS) - 70eV, Positivesplash10-000i-5384590000-954f20357dc689aab130JSpectraViewer
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 10V, Positivesplash10-066s-1390000000-8a52d6755935e91be345JSpectraViewer
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 20V, Positivesplash10-03di-9730000000-8e7df34a65b316df695eJSpectraViewer
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 40V, Positivesplash10-03di-9800000000-8768229ecc0345cd843aJSpectraViewer
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 10V, Negativesplash10-000i-9340000000-9e14b4f8a6d8f44c6ad6JSpectraViewer
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 20V, Negativesplash10-0a4i-9220000000-2ac584cea0c0d26bc11fJSpectraViewer
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 40V, Negativesplash10-0a4i-9200000000-dd74fa78262e5a7d35e0JSpectraViewer
Toxicity Profile
Route of ExposureIntravenous. Poor oral absorption (17-25%).
Mechanism of ToxicityStreptozotocin is a naturally occurring chemical that is particularly toxic to the insulin-producing beta cells of the pancreas. It is used in medical research to produce an animal model for Type 1 diabetes in large dose as well as Type 2 diabetes with multiple low doses. Streptozotocin is similar enough to glucose to be transported into the cell by the glucose transport protein GLUT2, but is not recognized by the other glucose transporters. This explains its relative toxicity to beta cells, since these cells have relatively high levels of GLUT2. Streptozotocin is a glucosamine-nitrosourea (i.e. alkylating) compound. As with other alkylating agents in the nitrosourea class, it is toxic to cells by causing damage to the DNA, though other mechanisms may also contribute.
MetabolismPrimarily hepatic Route of Elimination: As much as 20% of the drug (or metabolites containing an N-nitrosourea group) is metabolized and/or excreted by the kidney. Half Life: 5-15 minutes
Toxicity ValuesNot Available
Lethal DoseNot Available
Carcinogenicity (IARC Classification)2B, possibly carcinogenic to humans. (8)
Uses/SourcesFor the treatment of malignant neoplasms of pancreas (metastatic islet cell carcinoma).
Minimum Risk LevelNot Available
Health EffectsAntibiotic resistance
SymptomsSymptoms of overdose include nausea and vomiting, anorexia, myelosuppression; and nephrotoxicity.
TreatmentNot Available
Normal Concentrations
Not Available
Abnormal Concentrations
Not Available
DrugBank IDDB00428
HMDB IDHMDB14572
PubChem Compound ID29327
ChEMBL IDCHEMBL1651906
ChemSpider ID27273
KEGG IDC07313
UniProt IDNot Available
OMIM ID
ChEBI ID9288
BioCyc IDNot Available
CTD IDNot Available
Stitch IDStreptozocin
PDB IDNot Available
ACToR IDNot Available
Wikipedia LinkStreptozocin
References
Synthesis ReferenceNot Available
MSDSLink
General References
  1. Brentjens R, Saltz L: Islet cell tumors of the pancreas: the medical oncologist's perspective. Surg Clin North Am. 2001 Jun;81(3):527-42. [11459269 ]
  2. Wang Z, Gleichmann H: GLUT2 in pancreatic islets: crucial target molecule in diabetes induced with multiple low doses of streptozotocin in mice. Diabetes. 1998 Jan;47(1):50-6. [9421374 ]
  3. Schnedl WJ, Ferber S, Johnson JH, Newgard CB: STZ transport and cytotoxicity. Specific enhancement in GLUT2-expressing cells. Diabetes. 1994 Nov;43(11):1326-33. [7926307 ]
  4. VAVRA JJ, DEBOER C, DIETZ A, HANKA LJ, SOKOLSKI WT: Streptozotocin, a new antibacterial antibiotic. Antibiot Annu. 1959-1960;7:230-5. [13841501 ]
  5. Mansford KR, Opie L: Comparison of metabolic abnormalities in diabetes mellitus induced by streptozotocin or by alloxan. Lancet. 1968 Mar 30;1(7544):670-1. [4170654 ]
  6. Drugs.com [Link]
  7. BC Breast Cancer Agency (2007). Streptozocin. [Link]
  8. International Agency for Research on Cancer (2014). IARC Monographs on the Evaluation of Carcinogenic Risks to Humans. [Link]
Gene Regulation
Up-Regulated Genes
GeneGene SymbolGene IDInteractionChromosomeDetails
Down-Regulated Genes
GeneGene SymbolGene IDInteractionChromosomeDetails

Targets

General Function:
Hexose transmembrane transporter activity
Specific Function:
Facilitative glucose transporter. This isoform likely mediates the bidirectional transfer of glucose across the plasma membrane of hepatocytes and is responsible for uptake of glucose by the beta cells; may comprise part of the glucose-sensing mechanism of the beta cell. May also participate with the Na(+)/glucose cotransporter in the transcellular transport of glucose in the small intestine and kidney.
Gene Name:
SLC2A2
Uniprot ID:
P11168
Molecular Weight:
57488.955 Da
References
  1. Wang Z, Gleichmann H: GLUT2 in pancreatic islets: crucial target molecule in diabetes induced with multiple low doses of streptozotocin in mice. Diabetes. 1998 Jan;47(1):50-6. [9421374 ]
  2. Schnedl WJ, Ferber S, Johnson JH, Newgard CB: STZ transport and cytotoxicity. Specific enhancement in GLUT2-expressing cells. Diabetes. 1994 Nov;43(11):1326-33. [7926307 ]
General Function:
Hyalurononglucosaminidase activity
Specific Function:
Isoform 1: Cleaves GlcNAc but not GalNAc from O-glycosylated proteins. Can use p-nitrophenyl-beta-GlcNAc and 4-methylumbelliferone-GlcNAc as substrates but not p-nitrophenyl-beta-GalNAc or p-nitrophenyl-alpha-GlcNAc (in vitro) (PubMed:11148210). Does not bind acetyl-CoA and does not have histone acetyltransferase activity (PubMed:24088714).Isoform 3: Cleaves GlcNAc but not GalNAc from O-glycosylated proteins. Can use p-nitrophenyl-beta-GlcNAc as substrate but not p-nitrophenyl-beta-GalNAc or p-nitrophenyl-alpha-GlcNAc (in vitro), but has about six times lower specific activity than isoform 1.
Gene Name:
MGEA5
Uniprot ID:
O60502
Molecular Weight:
102914.215 Da
References
  1. Pathak S, Dorfmueller HC, Borodkin VS, van Aalten DM: Chemical dissection of the link between streptozotocin, O-GlcNAc, and pancreatic cell death. Chem Biol. 2008 Aug 25;15(8):799-807. doi: 10.1016/j.chembiol.2008.06.010. [18721751 ]
3. DNA
General Function:
Used for biological information storage.
Specific Function:
DNA contains the instructions needed for an organism to develop, survive and reproduce.
Molecular Weight:
2.15 x 1012 Da
References
  1. Bennett RA, Pegg AE: Alkylation of DNA in rat tissues following administration of streptozotocin. Cancer Res. 1981 Jul;41(7):2786-90. [6454479 ]