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Identification
NameStreptozocin
Accession NumberDB00428  (APRD00209)
Typesmall molecule
Groupsapproved
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
Synonyms
SynonymLanguageCode
2-Deoxy-2-(((methylnitrosoamino)carbonyl)amino)-D-glucopyranoseNot AvailableNot Available
2-Deoxy-2-(3-methyl-3-nitrosoureido)-D-glucopyranoseNot AvailableNot Available
EstreptozocinaNot AvailableNot Available
N-D-Glucosyl-(2)-n'-nitrosomethylureaNot AvailableNot Available
N-D-Glucosyl-(2)-n'-nitrosomethylharnstoffNot AvailableNot Available
StreptozocinNot AvailableINN, USAN
StreptozocineFrenchINN
StreptozociniumNot AvailableNot Available
StreptozocinumLatinINN
StreptozotocinNot AvailableNot Available
ZanosarNot AvailableNot Available
SaltsNot Available
Brand names
NameCompany
ZanosarNot Available
Brand mixturesNot Available
Categories
CAS number18883-66-4
WeightAverage: 265.2206
Monoisotopic: 265.090999849
Chemical FormulaC8H15N3O7
InChI KeyZSJLQEPLLKMAKR-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
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
Mass SpecNot Available
Taxonomy
KingdomOrganic Compounds
SuperclassOrganooxygen Compounds
ClassCarbohydrates and Carbohydrate Conjugates
SubclassAmino Sugars
Direct parentAmino Sugars
Alternative parentsHexoses; N-methylnitrosoureas; Oxanes; Semicarbazides; 1,2-Diols; Hemiacetals; Secondary Alcohols; Primary Alcohols; Polyamines
Substituentsn-methylnitrosourea; oxane; monosaccharide; nitrosourea; semicarbazide; polyol; hemiacetal; 1,2-diol; secondary alcohol; ether; polyamine; primary alcohol; amine; alcohol; organonitrogen compound
Classification descriptionThis compound belongs to the amino sugars. These are sugars having one alcoholic hydroxy group replaced by an amino group; systematically known as x-amino-x-deoxymonosaccharides. These compounds do not include Glycosylamines.
Pharmacology
IndicationFor the treatment of malignant neoplasms of pancreas (metastatic islet cell carcinoma).
PharmacodynamicsStreptozocin 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 actionAlthough 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.
AbsorptionPoor oral absorption (17-25%)
Volume of distributionNot Available
Protein bindingNot Available
Metabolism

Primarily hepatic

Route of eliminationAs much as 20% of the drug (or metabolites containing an N-nitrosourea group) is metabolized and/or excreted by the kidney.
Half life5-15 minutes
ClearanceNot Available
ToxicitySymptoms of overdose include nausea and vomiting, anorexia, myelosuppression; and nephrotoxicity.
Affected organisms
  • Humans and other mammals
PathwaysNot Available
SNP Mediated EffectsNot Available
SNP Mediated Adverse Drug ReactionsNot Available
ADMET
Predicted ADMET features
Property Value Probability
Human Intestinal Absorption - 0.8406
Blood Brain Barrier - 0.9659
Caco-2 permeable - 0.6495
P-glycoprotein substrate Non-substrate 0.6244
P-glycoprotein inhibitor I Non-inhibitor 0.7667
P-glycoprotein inhibitor II Non-inhibitor 0.9787
Renal organic cation transporter Non-inhibitor 0.9509
CYP450 2C9 substrate Non-substrate 0.6998
CYP450 2D6 substrate Non-substrate 0.846
CYP450 3A4 substrate Non-substrate 0.5462
CYP450 1A2 substrate Non-inhibitor 0.9046
CYP450 2C9 substrate Non-inhibitor 0.9071
CYP450 2D6 substrate Non-inhibitor 0.9231
CYP450 2C19 substrate Non-inhibitor 0.9026
CYP450 3A4 substrate Non-inhibitor 0.9636
CYP450 inhibitory promiscuity Low CYP Inhibitory Promiscuity 0.9893
Ames test AMES toxic 0.9107
Carcinogenicity Non-carcinogens 0.9182
Biodegradation Ready biodegradable 0.7191
Rat acute toxicity 2.6715 LD50, mol/kg Not applicable
hERG inhibition (predictor I) Weak inhibitor 0.793
hERG inhibition (predictor II) Non-inhibitor 0.9288
Pharmacoeconomics
Manufacturers
  • Teva parenteral medicines inc
Packagers
Dosage forms
FormRouteStrength
Powder, for solutionIntravenous
Prices
Unit descriptionCostUnit
Zanosar 1 gm powder vial78.82USDvial
DrugBank does not sell nor buy drugs. Pricing information is supplied for informational purposes only.
PatentsNot Available
Properties
Statesolid
Experimental Properties
PropertyValueSource
melting point115 °CPhysProp
water solubility5070 mg/LNot Available
logP-1.45HANSCH,C ET AL. (1995)
Predicted Properties
PropertyValueSource
water solubility3.35e+01 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 area151.92ChemAxon
rotatable bond count3ChemAxon
refractivity55.96ChemAxon
polarizability23.74ChemAxon
number of rings1ChemAxon
bioavailability1ChemAxon
rule of fiveYesChemAxon
Ghose filterNoChemAxon
Veber's ruleNoChemAxon
MDDR-like ruleNoChemAxon
Spectra
SpectraNot Available
References
Synthesis ReferenceNot 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
ResourceLink
KEGG DrugD05932
PubChem Compound29327
PubChem Substance46508872
ChemSpider27273
ChEBI9288
ChEMBLCHEMBL1651906
Therapeutic Targets DatabaseDAP000984
PharmGKBPA451514
Drug Product Database622141
RxListhttp://www.rxlist.com/cgi/generic/zanosar.htm
Drugs.comhttp://www.drugs.com/cdi/streptozocin.html
WikipediaStreptozocin
ATC CodesL01AD04
AHFS Codes
  • 10:00.00
PDB EntriesNot Available
FDA labelNot Available
MSDSshow(76.6 KB)
Interactions
Drug Interactions
Drug
BendamustineIncreases toxicity through pharmacodynamic synergism. Additive myelosuppression.
TrastuzumabTrastuzumab may increase the risk of neutropenia and anemia. Monitor closely for signs and symptoms of adverse events.
Food InteractionsNot Available

Targets

1. DNA

Kind: nucleotide

Organism: Human

Pharmacological action: yes

Actions: cross-linking/alkylation

Components

Name UniProt ID Details

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

Kind: protein

Organism: Human

Pharmacological action: unknown

Actions: ligand

Components

Name UniProt ID Details
Solute carrier family 2, facilitated glucose transporter member 2 P11168 Details

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

Kind: protein

Organism: Bacteroides thetaiotaomicron (strain ATCC 29148 / DSM 2079 / NCTC 10582 / E50 / VPI-5482)

Pharmacological action: yes

Actions: antagonist

Components

Name UniProt ID Details
O-GlcNAcase BT_4395 Q89ZI2 Details

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

Kind: protein

Organism: Human

Pharmacological action: unknown

Actions: inducer

Components

Name UniProt ID Details
Cytochrome P450 1A1 P04798 Details

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

Kind: protein

Organism: Human

Pharmacological action: unknown

Actions: inducer

Components

Name UniProt ID Details
Cytochrome P450 1A2 P05177 Details

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

Kind: protein

Organism: Human

Pharmacological action: unknown

Actions: inducer

Components

Name UniProt ID Details
Cytochrome P450 2E1 P05181 Details

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

Kind: protein

Organism: Human

Pharmacological action: unknown

Actions: inducer

Components

Name UniProt ID Details
Multidrug resistance protein 1 P08183 Details

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

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Drug created on June 13, 2005 07:24 / Updated on September 16, 2013 17:10