Streptozocin

Identification

Summary

Streptozocin is a nitrosourea antineoplastic agent used in the treatment of metastatic pancreatic islet cell carcinoma.

Brand Names
Zanosar
Generic Name
Streptozocin
DrugBank Accession Number
DB00428
Background

An antibiotic that is produced by Stretomyces achromogenes. It is used as an antineoplastic agent and to induce diabetes in experimental animals.

Type
Small Molecule
Groups
Approved, Investigational
Structure
Weight
Average: 265.2206
Monoisotopic: 265.090999849
Chemical Formula
C8H15N3O7
Synonyms
  • 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
  • Streptozocin
  • Streptozocine
  • Streptozocinium
  • Streptozocinum
  • Streptozotocin

Pharmacology

Indication

For the treatment of malignant neoplasms of pancreas (metastatic islet cell carcinoma).

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Associated Conditions
Indication TypeIndicationCombined Product DetailsApproval LevelAge GroupPatient CharacteristicsDose Form
Treatment ofMetastatic islet cell carcinoma•••••••••••••••••••••• ••••••• ••• ••••••••
Contraindications & Blackbox Warnings
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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.

TargetActionsOrganism
AO-GlcNAcase BT_4395
antagonist
Bacteroides thetaiotaomicron (strain ATCC 29148 / DSM 2079 / NCTC 10582 / E50 / VPI-5482)
ADNA
cross-linking/alkylation
Humans
USolute carrier family 2, facilitated glucose transporter member 2
ligand
Humans
UBifunctional protein NCOATNot AvailableHumans
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

Adverse Effects
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Toxicity

Symptoms of overdose include nausea and vomiting, anorexia, myelosuppression; and nephrotoxicity.

Pathways
Not Available
Pharmacogenomic Effects/ADRs
Not Available

Interactions

Drug Interactions
This information should not be interpreted without the help of a healthcare provider. If you believe you are experiencing an interaction, contact a healthcare provider immediately. The absence of an interaction does not necessarily mean no interactions exist.
DrugInteraction
AbataceptThe risk or severity of adverse effects can be increased when Streptozocin is combined with Abatacept.
AbciximabThe risk or severity of bleeding can be increased when Abciximab is combined with Streptozocin.
AcenocoumarolThe risk or severity of bleeding can be increased when Acenocoumarol is combined with Streptozocin.
AcetaminophenStreptozocin may increase the hepatotoxic activities of Acetaminophen.
Acetylsalicylic acidThe risk or severity of bleeding can be increased when Acetylsalicylic acid is combined with Streptozocin.
Food Interactions
No interactions found.

Products

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Brand Name Prescription Products
NameDosageStrengthRouteLabellerMarketing StartMarketing EndRegionImage
ZanosarPowder, for solution100 mg/1mLIntravenousTeva Parenteral Medicines, Inc.2003-12-03Not applicableUS flag
ZanosarPowder, for solution1 g/10mLIntravenousEsteve Pharmaceuticals, S.A.2023-02-01Not applicableUS flag
Zanosar Sterile PowderPowder, for solution1 g / vialIntravenousPaladin Labs Inc1985-12-312017-12-19Canada flag
Unapproved/Other Products
NameIngredientsDosageRouteLabellerMarketing StartMarketing EndRegionImage
ZanosarStreptozocin (1 g/10mL)Powder, for solutionIntravenousEsteve Pharmaceuticals, S.A.2023-02-01Not applicableUS flag

Categories

ATC Codes
L01AD04 — Streptozocin
Drug Categories
Chemical TaxonomyProvided by Classyfire
Description
This compound 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.
Kingdom
Organic compounds
Super Class
Organic oxygen compounds
Class
Organooxygen compounds
Sub Class
Carbohydrates and carbohydrate conjugates
Direct Parent
Hexoses
Alternative Parents
N-methylnitrosoureas / Oxanes / Semicarbazides / Nitrosamides / Secondary alcohols / Hemiacetals / Polyols / Oxacyclic compounds / Primary alcohols / Organopnictogen compounds
show 3 more
Substituents
Alcohol / Aliphatic heteromonocyclic compound / Carbonic acid derivative / Carbonyl group / Hemiacetal / Hexose monosaccharide / Hydrocarbon derivative / N-methylnitrosourea / Nitrosamide / Nitrosourea
show 13 more
Molecular Framework
Aliphatic heteromonocyclic compounds
External Descriptors
N-nitrosoureas, N-acylglucosamine (CHEBI:9288)
Affected organisms
  • Humans and other mammals

Chemical Identifiers

UNII
8H27GUR065
CAS number
66395-18-4
InChI Key
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[C@H]1[C@@H](O)O[C@H](CO)[C@@H](O)[C@@H]1O

References

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. [Article]
  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. [Article]
  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. [Article]
  4. VAVRA JJ, DEBOER C, DIETZ A, HANKA LJ, SOKOLSKI WT: Streptozotocin, a new antibacterial antibiotic. Antibiot Annu. 1959-1960;7:230-5. [Article]
  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. [Article]
  6. Link [Link]
Human Metabolome Database
HMDB0014572
KEGG Drug
D05932
KEGG Compound
C07313
PubChem Compound
29327
PubChem Substance
46508872
ChemSpider
27273
RxNav
10114
ChEBI
9288
ChEMBL
CHEMBL1603
ZINC
ZINC000003977737
Therapeutic Targets Database
DAP000984
PharmGKB
PA451514
RxList
RxList Drug Page
Drugs.com
Drugs.com Drug Page
Wikipedia
Streptozotocin
MSDS
Download (76.6 KB)

Clinical Trials

Clinical Trials

Pharmacoeconomics

Manufacturers
  • Teva parenteral medicines inc
Packagers
  • Pharmacia Inc.
  • Prescript Pharmaceuticals
  • Teva Pharmaceutical Industries Ltd.
Dosage Forms
FormRouteStrength
Injection, powder, for solution1 G
Powder, for solutionIntravenous1 g/10mL
Powder, for solutionIntravenous100 mg/1mL
Powder, for solutionIntravenous1 g / vial
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.
Patents
Not Available

Properties

State
Solid
Experimental Properties
PropertyValueSource
melting point (°C)115 °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 FilterNoChemaxon
Veber's RuleNoChemaxon
MDDR-like RuleNoChemaxon
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)

Spectra

Mass Spec (NIST)
Not Available
Spectra
SpectrumSpectrum TypeSplash Key
Predicted GC-MS Spectrum - GC-MSPredicted GC-MSsplash10-02mj-5940000000-8fb8f1885498bea8bc01
Predicted MS/MS Spectrum - 10V, Positive (Annotated)Predicted LC-MS/MSsplash10-000t-1090000000-a3712cb6ab0e1446c94b
Predicted MS/MS Spectrum - 10V, Negative (Annotated)Predicted LC-MS/MSsplash10-0fdp-0970000000-18adf5e6f0210193048f
Predicted MS/MS Spectrum - 20V, Positive (Annotated)Predicted LC-MS/MSsplash10-0006-9000000000-e5d735487de79e1c98ca
Predicted MS/MS Spectrum - 20V, Negative (Annotated)Predicted LC-MS/MSsplash10-000x-9200000000-3be569e0778266d6e524
Predicted MS/MS Spectrum - 40V, Positive (Annotated)Predicted LC-MS/MSsplash10-03di-9300000000-6d1ab1360a5427f5d979
Predicted MS/MS Spectrum - 40V, Negative (Annotated)Predicted LC-MS/MSsplash10-0a4i-9200000000-7b91e03077a9104670f9
Predicted 1H NMR Spectrum1D NMRNot Applicable
Predicted 13C NMR Spectrum1D NMRNot Applicable
Chromatographic Properties
Collision Cross Sections (CCS)
AdductCCS Value (Å2)Source typeSource
[M-H]-159.5292799
predicted
DarkChem Lite v0.1.0
[M-H]-150.1463325
predicted
DarkChem Lite v0.1.0
[M-H]-164.7824799
predicted
DarkChem Lite v0.1.0
[M-H]-157.69673
predicted
DeepCCS 1.0 (2019)
[M+H]+159.1744799
predicted
DarkChem Lite v0.1.0
[M+H]+155.740934
predicted
DarkChem Lite v0.1.0
[M+H]+165.3517799
predicted
DarkChem Lite v0.1.0
[M+H]+160.0923
predicted
DeepCCS 1.0 (2019)
[M+Na]+159.2871799
predicted
DarkChem Lite v0.1.0
[M+Na]+163.7324253
predicted
DarkChem Lite v0.1.0
[M+Na]+164.8657799
predicted
DarkChem Lite v0.1.0
[M+Na]+166.89705
predicted
DeepCCS 1.0 (2019)

Targets

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insights and accelerate drug research.
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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
Uniprot Name
O-GlcNAcase BT_4395
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. [Article]
Kind
Nucleotide
Organism
Humans
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.
References
  1. Bennett RA, Pegg AE: Alkylation of DNA in rat tissues following administration of streptozotocin. Cancer Res. 1981 Jul;41(7):2786-90. [Article]
Kind
Protein
Organism
Humans
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 c...
Gene Name
SLC2A2
Uniprot ID
P11168
Uniprot Name
Solute carrier family 2, facilitated glucose transporter member 2
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. [Article]
  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. [Article]
Kind
Protein
Organism
Humans
Pharmacological action
Unknown
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-nitrop...
Gene Name
MGEA5
Uniprot ID
O60502
Uniprot Name
Protein O-GlcNAcase
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. [Article]

Enzymes

Kind
Protein
Organism
Humans
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 un...
Gene Name
CYP1A1
Uniprot ID
P04798
Uniprot Name
Cytochrome P450 1A1
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. [Article]
Kind
Protein
Organism
Humans
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 un...
Gene Name
CYP1A2
Uniprot ID
P05177
Uniprot Name
Cytochrome P450 1A2
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. [Article]
Kind
Protein
Organism
Humans
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 ...
Gene Name
CYP2E1
Uniprot ID
P05181
Uniprot Name
Cytochrome P450 2E1
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. [Article]

Transporters

Kind
Protein
Organism
Humans
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
Uniprot Name
Multidrug resistance protein 1
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. [Article]

Drug created at June 13, 2005 13:24 / Updated at March 18, 2024 16:48