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Identification
Name Streptozocin
Accession Number DB00428 (APRD00209)
Type small molecule
Groups approved
Description

An antibiotic that is produced by Stretomyces achromogenes. It is used as an antineoplastic agent and to induce diabetes in experimental animals. [PubChem]
Structure Thumb
Download: MOL | SDF | SMILES | InChI
Display: 2D Structure | 3D Structure
Synonyms Not Available
Salts Not Available
Brand names
Name Company
Streptozocin [Usan:Inn]
Streptozocine [INN-French]
Streptozocinium [Latin]
Streptozocinum [INN-Latin]
STREPTOZOTOCIN
STRZ
Zanosar
Brand mixtures Not Available
Categories
  • Antineoplastic Agents
  • Antibiotics
  • Antibiotics, Antineoplastic
CAS number 18883-66-4
Weight Average: 265.2206
Monoisotopic: 265.090999849
Chemical Formula C8H15N3O7
InChI Key InChIKey=ZSJLQEPLLKMAKR-GKHCUFPYSA-N
InChI
InChI=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
Plain Text
IUPAC Name
3-methyl-3-nitroso-1-[(2S,3R,4R,5S,6R)-2,4,5-trihydroxy-6-(hydroxymethyl)oxan-3-yl]urea
SMILES
CN(N=O)C(=O)N[C@H]1[C@@H](O)O[C@H](CO)[C@@H](O)[C@@H]1O
Plain Text
Mass Spec Not Available
Taxonomy
Kingdom Organic
Classes
  • Carbohydrates
Substructures
  • Carbohydrates
  • Aminoglycosides
  • Glycerol and Derivatives
  • Hydroxy Compounds
  • Pyrans
  • Oxoazaniums
  • Acetals and Derivatives
  • Nitroso Compounds
  • Ethers
  • Ureas and Derivatives
  • Alcohols and Polyols
  • Heterocyclic compounds
  • Semicarbazides
  • Hydrazine Derivatives
  • Amynoglycosides
Pharmacology
Indication For the treatment of malignant neoplasms of pancreas (metastatic islet cell carcinoma).
Pharmacodynamics Streptozocin is an antitumour antibiotic consisting of a nitrosourea moiety interposed between a methyl group and a glucosamine. Streptozocin is indicated in the treatment of metastatic islet cell carcinoma of the pancreas. Streptozocin inhibits DNA synthesis in bacterial and mammalian cells. In bacterial cells, a specific interaction with cytosine moieties leads to degradation of DNA. The biochemical mechanism leading to mammalian cell death has not been definitely established; streptozocin inhibits cell proliferation at a considerably lower level than that needed to inhibit precursor incorporation into DNA or to inhibit several of the enzymes involved in DNA synthesis. Although streptozocin inhibits the progression of cells into mitosis, no specific phase of the cell cycle is particularly sensitive to its lethal effects.
Mechanism of action 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.
Absorption Poor oral absorption (17-25%)
Volume of distribution Not Available
Protein binding Not Available
Metabolism
Primarily 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
Clearance Not Available
Toxicity Symptoms of overdose include nausea and vomiting, anorexia, myelosuppression; and nephrotoxicity.
Affected organisms
  • Humans and other mammals
Pathways Not Available
Pharmacoeconomics
Manufacturers
  • Teva parenteral medicines inc
Packagers
Dosage forms
Form Route Strength
Powder, for solution Intravenous
Prices
Unit description Cost Unit
Zanosar 1 gm powder vial 78.82 USD vial
DrugBank does not sell nor buy drugs. Pricing information is supplied for informational purposes only.
Patents Not Available
Properties
State solid
Experimental Properties
Property Value Source
melting point 115 °C PhysProp
water solubility 5070 mg/L Not Available
logP -1.45 HANSCH,C ET AL. (1995)
Predicted Properties
Property Value Source
water solubility 3.35e+01 g/l ALOGPS
logP -1.7 ALOGPS
logP -2.7 ChemAxon
logS -0.9 ALOGPS
pKa (strongest acidic) 11.43 ChemAxon
pKa (strongest basic) -3 ChemAxon
physiological charge 0 ChemAxon
hydrogen acceptor count 7 ChemAxon
hydrogen donor count 5 ChemAxon
polar surface area 151.92 ChemAxon
rotatable bond count 3 ChemAxon
refractivity 55.96 ChemAxon
polarizability 23.74 ChemAxon
References
Synthesis Reference Not Available
General Reference
  1. Link
  2. 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. Pubmed
  3. 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. Pubmed
  4. 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. Pubmed
  5. VAVRA JJ, DEBOER C, DIETZ A, HANKA LJ, SOKOLSKI WT: Streptozotocin, a new antibacterial antibiotic. Antibiot Annu. 1959-1960;7:230-5. Pubmed
  6. 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. Pubmed
External Links
Resource Link
KEGG Drug D05932 Link_out
PubChem Compound 29327 Link_out
PubChem Substance 46508872 Link_out
ChemSpider 27273 Link_out
ChEBI 9288 Link_out
ChEMBL 9288 Link_out
Therapeutic Targets Database DAP000984 Link_out
PharmGKB PA451514 Link_out
Drug Product Database 622141 Link_out
RxList http://www.rxlist.com/cgi/generic/zanosar.htm Link_out
Drugs.com http://www.drugs.com/cdi/streptozocin.html Link_out
Wikipedia http://en.wikipedia.org/wiki/Streptozocin Link_out
ATC Codes
  • L01AD04
AHFS Codes
  • 10:00.00
PDB Entries Not Available
FDA label Not Available
MSDS show (76.6 KB)
Interactions
Drug Interactions
Drug Interaction
Bendamustine Increases toxicity through pharmacodynamic synergism. Additive myelosuppression.
Trastuzumab Trastuzumab may increase the risk of neutropenia and anemia. Monitor closely for signs and symptoms of adverse events.
Food Interactions Not Available
Targets

1. DNA

Pharmacological action: yes
Actions: cross-linking/alkylation

DNA is the molecule of heredity, as it is responsible for the genetic propagation of most inherited traits. It is a polynucleic acid that carries genetic information on cell growth, division, and function. DNA consists of two long strands of nucleotides twisted into a double helix and held together by hydrogen bonds. The sequence of nucleotides determines hereditary characteristics. Each strand serves as the template for subsequent DNA replication and as a template for mRNA production, leading to protein synthesis via ribosomes.

Gene Sequence: FASTA

References:
  1. Bennett RA, Pegg AE: Alkylation of DNA in rat tissues following administration of streptozotocin. Cancer Res. 1981 Jul;41(7):2786-90. Pubmed

2. Solute carrier family 2, facilitated glucose transporter member 2

Pharmacological action: unknown
Actions: ligand

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

Organism class: human
UniProt ID: P11168 Link_out
Gene: SLC2A2 Link_out
Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report Link_out

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. Pubmed
  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. Pubmed

3. O-GlcNAcase BT_4395

Pharmacological action: yes
Actions: antagonist

Biological function unknown. Capable of hydrolyzing the glycosidic link of O-GlcNAcylated proteins

Organism class: bacterial
UniProt ID: Q89ZI2 Link_out
Gene: BT_4395
Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report Link_out

References:
  1. He Y, Martinez-Fleites C, Bubb A, Gloster TM, Davies GJ: Structural insight into the mechanism of streptozotocin inhibition of O-GlcNAcase. Carbohydr Res. 2009 Mar 31;344(5):627-31. doi: 10.1016/j.carres.2008.12.007. Epub 2008 Dec 13. Pubmed
Enzymes

1. Cytochrome P450 1A1

Actions: inducer

Cytochromes P450 are a group of heme-thiolate monooxygenases. In liver microsomes, this enzyme is involved in an NADPH-dependent electron transport pathway. It oxidizes a variety of structurally unrelated compounds, including steroids, fatty acids, and xenobiotics

UniProt ID: P04798 Link_out
Gene: CYP1A1 Link_out
Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report Link_out

References:
  1. Choi YH, Lee AK, Bae SK, Kim SO, Lee MG: Pharmacokinetics of 5-fluorouracil in rats with diabetes mellitus induced by streptozotocin. Biopharm Drug Dispos. 2005 Apr;26(3):93-8. Pubmed

2. Cytochrome P450 1A2

Actions: inducer

Cytochromes P450 are a group of heme-thiolate monooxygenases. In liver microsomes, this enzyme is involved in an NADPH-dependent electron transport pathway. It oxidizes a variety of structurally unrelated compounds, including steroids, fatty acids, and xenobiotics. Most active in catalyzing 2-hydroxylation. Caffeine is metabolized primarily by cytochrome CYP1A2 in the liver through an initial N3-demethylation. Also acts in the metabolism of aflatoxin B1 and acetaminophen

UniProt ID: P05177 Link_out
Gene: CYP1A2
Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report Link_out

References:
  1. Choi YH, Lee AK, Bae SK, Kim SO, Lee MG: Pharmacokinetics of 5-fluorouracil in rats with diabetes mellitus induced by streptozotocin. Biopharm Drug Dispos. 2005 Apr;26(3):93-8. Pubmed

3. Cytochrome P450 2E1

Actions: inducer

Metabolizes several precarcinogens, drugs, and solvents to reactive metabolites. Inactivates a number of drugs and xenobiotics and also bioactivates many xenobiotic substrates to their hepatotoxic or carcinogenic forms

UniProt ID: P05181 Link_out
Gene: CYP2E1 Link_out
Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report Link_out

References:
  1. Kataoka S, Yasui H, Hiromura M, Sakurai H: Effect of insulin-mimetic vanadyl sulfate on cytochrome P450 2E1-dependent p-nitrophenol hydroxylation in the liver microsomes of streptozotocin-induced type 1 diabetic rats. Life Sci. 2005 Oct 14;77(22):2814-29. Pubmed
Transporters

1. Multidrug resistance protein 1

Actions: inducer

Energy-dependent efflux pump responsible for decreased drug accumulation in multidrug-resistant cells

UniProt ID: P08183 Link_out
Gene: ABCB1 Link_out
Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report Link_out

References:
  1. Brady JM, Cherrington NJ, Hartley DP, Buist SC, Li N, Klaassen CD: Tissue distribution and chemical induction of multiple drug resistance genes in rats. Drug Metab Dispos. 2002 Jul;30(7):838-44. Pubmed
Comments
Drug created on June 13, 2005 07:24 / Updated on February 08, 2013 16:19