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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
2-Deoxy-2-(((methylnitrosoamino)carbonyl)amino)-D-glucopyranose
2-Deoxy-2-(3-methyl-3-nitrosoureido)-D-glucopyranose
Estreptozocina
N-D-Glucosyl-(2)-n'-nitrosomethylurea
N-D-Glucosyl-(2)-n'-nitrosomethylharnstoff
Streptozocin
Streptozocine
Streptozocinium
Streptozocinum
Streptozotocin
Zanosar
External Identifiers Not Available
Approved Prescription Products
NameDosageStrengthRouteLabellerMarketing StartMarketing End
Zanosarpowder, for solution100 mg/mLintravenousTeva Parenteral Medicines, Inc.2003-12-03Not applicableUs
Zanosar Sterile Powderpowder for solution1 gintravenousPaladin Labs Inc1985-12-31Not applicableCanada
Approved Generic Prescription ProductsNot Available
Approved Over the Counter ProductsNot Available
Unapproved/Other Products Not Available
International BrandsNot Available
Brand mixturesNot Available
SaltsNot Available
Categories
UNII5W494URQ81
CAS number18883-66-4
WeightAverage: 265.2206
Monoisotopic: 265.090999849
Chemical FormulaC8H15N3O7
InChI KeyInChIKey=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
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[[email protected]]1[C@@H](O)O[[email protected]](CO)[C@@H](O)[C@@H]1O
Taxonomy
DescriptionThis compound belongs to the class of organic compounds known as 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.
KingdomOrganic compounds
Super ClassOrganooxygen compounds
ClassCarbohydrates and carbohydrate conjugates
Sub ClassAminosaccharides
Direct ParentAmino sugars
Alternative Parents
Substituents
  • Glucosamine
  • Amino sugar
  • N-methylnitrosourea
  • Oxane
  • Nitrosourea
  • Monosaccharide
  • Nitrosamide
  • Semicarbazide
  • Organic nitrosamine
  • Secondary alcohol
  • Polyol
  • N-nitroso compound
  • Hemiacetal
  • 1,2-diol
  • Oxacycle
  • Organoheterocyclic compound
  • Hydrocarbon derivative
  • Primary alcohol
  • Organonitrogen compound
  • Alcohol
  • Aliphatic heteromonocyclic compound
Molecular FrameworkAliphatic heteromonocyclic compounds
External Descriptors
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.
Related Articles
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
PropertyValueProbability
Human Intestinal Absorption-0.8406
Blood Brain Barrier-0.9659
Caco-2 permeable-0.6495
P-glycoprotein substrateNon-substrate0.6244
P-glycoprotein inhibitor INon-inhibitor0.7667
P-glycoprotein inhibitor IINon-inhibitor0.9787
Renal organic cation transporterNon-inhibitor0.9509
CYP450 2C9 substrateNon-substrate0.6998
CYP450 2D6 substrateNon-substrate0.846
CYP450 3A4 substrateNon-substrate0.5462
CYP450 1A2 substrateNon-inhibitor0.9046
CYP450 2C9 inhibitorNon-inhibitor0.9071
CYP450 2D6 inhibitorNon-inhibitor0.9231
CYP450 2C19 inhibitorNon-inhibitor0.9026
CYP450 3A4 inhibitorNon-inhibitor0.9636
CYP450 inhibitory promiscuityLow CYP Inhibitory Promiscuity0.9893
Ames testAMES toxic0.9107
CarcinogenicityNon-carcinogens0.9182
BiodegradationReady biodegradable0.7191
Rat acute toxicity2.6715 LD50, mol/kg Not applicable
hERG inhibition (predictor I)Weak inhibitor0.793
hERG inhibition (predictor II)Non-inhibitor0.9288
ADMET data is predicted using admetSAR, a free tool for evaluating chemical ADMET properties. (23092397 )
Pharmacoeconomics
Manufacturers
  • Teva parenteral medicines inc
Packagers
Dosage forms
FormRouteStrength
Powder, for solutionintravenous100 mg/mL
Powder for solutionintravenous1 g
Prices
Unit descriptionCostUnit
Zanosar 1 gm powder vial78.82USD vial
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 Solubility33.5 mg/mLALOGPS
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 Å2ChemAxon
Rotatable Bond Count3ChemAxon
Refractivity55.96 m3·mol-1ChemAxon
Polarizability23.74 Å3ChemAxon
Number of Rings1ChemAxon
Bioavailability1ChemAxon
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. 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: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. [PubMed: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. [PubMed:7926307 ]
  4. VAVRA JJ, DEBOER C, DIETZ A, HANKA LJ, SOKOLSKI WT: Streptozotocin, a new antibacterial antibiotic. Antibiot Annu. 1959-1960;7:230-5. [PubMed: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. [PubMed:4170654 ]
  6. Link [Link]
External Links
ATC CodesL01AD04
AHFS Codes
  • 10:00.00
PDB EntriesNot Available
FDA labelNot Available
MSDSDownload (76.6 KB)
Interactions
Drug Interactions
Drug
ClozapineThe risk or severity of adverse effects can be increased when Streptozocin is combined with Clozapine.
DenosumabThe risk or severity of adverse effects can be increased when Denosumab is combined with Streptozocin.
LeflunomideThe risk or severity of adverse effects can be increased when Streptozocin is combined with Leflunomide.
MetamizoleThe risk or severity of adverse effects can be increased when Metamizole is combined with Streptozocin.
NatalizumabThe risk or severity of adverse effects can be increased when Streptozocin is combined with Natalizumab.
PimecrolimusThe risk or severity of adverse effects can be increased when Pimecrolimus is combined with Streptozocin.
RoflumilastRoflumilast may increase the immunosuppressive activities of Streptozocin.
Sipuleucel-TThe therapeutic efficacy of Sipuleucel-T can be decreased when used in combination with Streptozocin.
TacrolimusThe risk or severity of adverse effects can be increased when Tacrolimus is combined with Streptozocin.
TofacitinibStreptozocin may increase the immunosuppressive activities of Tofacitinib.
TrastuzumabTrastuzumab may increase the neutropenic activities of Streptozocin.
Food InteractionsNot Available

Targets

1. DNA
Kind
Nucleotide
Organism
Human
Pharmacological action
yes
Actions
cross-linking/alkylation
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. [PubMed:6454479 ]
Kind
Protein
Organism
Human
Pharmacological action
unknown
Actions
ligand
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 an...
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. [PubMed: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. [PubMed:7926307 ]
Kind
Protein
Organism
Bacteroides thetaiotaomicron (strain ATCC 29148 / DSM 2079 / NCTC 10582 / E50 / VPI-5482)
Pharmacological action
yes
Actions
antagonist
General Function:
Beta-n-acetylglucosaminidase activity
Specific Function:
Can hydrolyze the glycosidic link of O-GlcNAcylated proteins. Can use p-nitrophenyl-beta-GlcNAc and 4-methylumbelliferone-GlcNAc as substrates (in vitro).
Gene Name:
Not Available
Uniprot ID:
Q89ZI2
Molecular Weight:
84484.62 Da
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:19217614 ]

Enzymes

Kind
Protein
Organism
Human
Pharmacological action
unknown
Actions
inducer
General Function:
Vitamin d 24-hydroxylase activity
Specific Function:
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.
Gene Name:
CYP1A1
Uniprot ID:
P04798
Molecular Weight:
58164.815 Da
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:15674819 ]
Kind
Protein
Organism
Human
Pharmacological action
unknown
Actions
inducer
General Function:
Oxidoreductase activity, acting on paired donors, with incorporation or reduction of molecular oxygen, reduced flavin or flavoprotein as one donor, and incorporation of one atom of oxygen
Specific Function:
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 N...
Gene Name:
CYP1A2
Uniprot ID:
P05177
Molecular Weight:
58293.76 Da
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:15674819 ]
Kind
Protein
Organism
Human
Pharmacological action
unknown
Actions
inducer
General Function:
Steroid hydroxylase activity
Specific Function:
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.
Gene Name:
CYP2E1
Uniprot ID:
P05181
Molecular Weight:
56848.42 Da
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:15964029 ]

Transporters

Kind
Protein
Organism
Human
Pharmacological action
unknown
Actions
inducer
General Function:
Xenobiotic-transporting atpase activity
Specific Function:
Energy-dependent efflux pump responsible for decreased drug accumulation in multidrug-resistant cells.
Gene Name:
ABCB1
Uniprot ID:
P08183
Molecular Weight:
141477.255 Da
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:12065443 ]
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Drug created on June 13, 2005 07:24 / Updated on September 16, 2013 17:10