Identification

Name
Streptozocin
Accession Number
DB00428  (APRD00209)
Type
Small Molecule
Groups
Approved, Investigational
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
Prescription Products
NameDosageStrengthRouteLabellerMarketing StartMarketing End
ZanosarPowder, for solution100 mg/1mLIntravenousTeva Parenteral Medicines, Inc.2003-12-03Not applicableUs
Zanosar Sterile PowderPowder, for solution1 gIntravenousPaladin Labs Inc1985-12-31Not applicableCanada
International/Other Brands
Zanosar
Categories
UNII
8H27GUR065
CAS number
18883-66-4
Weight
Average: 265.2206
Monoisotopic: 265.090999849
Chemical Formula
C8H15N3O7
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

Pharmacology

Indication

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

Associated Conditions
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
ADNA
cross-linking/alkylation
Human
USolute carrier family 2, facilitated glucose transporter member 2
ligand
Human
AO-GlcNAcase BT_4395
antagonist
Bacteroides thetaiotaomicron (strain ATCC 29148 / DSM 2079 / NCTC 10582 / E50 / VPI-5482)
UBifunctional protein NCOATNot AvailableHuman
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
Pharmacogenomic Effects/ADRs
Not Available

Interactions

Drug Interactions
DrugInteraction
2-MethoxyethanolThe risk or severity of adverse effects can be increased when Streptozocin is combined with 2-Methoxyethanol.
9-(N-methyl-L-isoleucine)-cyclosporin AThe risk or severity of adverse effects can be increased when Streptozocin is combined with 9-(N-methyl-L-isoleucine)-cyclosporin A.
AbataceptThe risk or severity of adverse effects can be increased when Abatacept is combined with Streptozocin.
AbemaciclibThe serum concentration of Abemaciclib can be decreased when it is combined with Streptozocin.
AbetimusThe risk or severity of adverse effects can be increased when Streptozocin is combined with Abetimus.
AcebutololThe serum concentration of Acebutolol can be decreased when it is combined with Streptozocin.
AcetaminophenThe serum concentration of Acetaminophen can be decreased when it is combined with Streptozocin.
Acetylsalicylic acidThe serum concentration of Acetylsalicylic acid can be decreased when it is combined with Streptozocin.
ActeosideThe risk or severity of adverse effects can be increased when Streptozocin is combined with Acteoside.
AdalimumabThe risk or severity of adverse effects can be increased when Adalimumab is combined with Streptozocin.
Food Interactions
Not Available

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. [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
Human Metabolome Database
HMDB0014572
KEGG Drug
D05932
KEGG Compound
C07313
PubChem Compound
29327
PubChem Substance
46508872
ChemSpider
27273
ChEBI
9288
ChEMBL
CHEMBL1603
Therapeutic Targets Database
DAP000984
PharmGKB
PA451514
RxList
RxList Drug Page
Drugs.com
Drugs.com Drug Page
Wikipedia
Streptozocin
ATC Codes
L01AD04 — Streptozocin
AHFS Codes
  • 10:00.00 — Antineoplastic Agents
MSDS
Download (76.6 KB)

Clinical Trials

Clinical Trials
PhaseStatusPurposeConditionsCount
1CompletedTreatmentColorectal Cancers1
2CompletedTreatmentAnaplastic Astrocytoma (AA) / Anaplastic Oligodendroglioma (AO) / Glioblastoma Multiforme (GBM) / Mixed Gliomas / Recurrent Brain Tumors1
2CompletedTreatmentCarcinoid tumour of the gastrointestinal tract / Islet Cell Tumor1
2CompletedTreatmentNeoplasms1
2Not Yet RecruitingTreatmentMalignant Neoplasm of Pancreas1
2TerminatedTreatmentMalignant Neoplasm of Pancreas1
3CompletedTreatmentCarcinoma, Adrenal Cortical1

Pharmacoeconomics

Manufacturers
  • Teva parenteral medicines inc
Packagers
  • Pharmacia Inc.
  • Prescript Pharmaceuticals
  • Teva Pharmaceutical Industries Ltd.
Dosage forms
FormRouteStrength
Powder, for solutionIntravenous100 mg/1mL
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.
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-MSNot Available
Predicted MS/MS Spectrum - 10V, Positive (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 20V, Positive (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 40V, Positive (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 10V, Negative (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 20V, Negative (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 40V, Negative (Annotated)Predicted LC-MS/MSNot Available

Taxonomy

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
Hexose monosaccharide / N-methylnitrosourea / Nitrosourea / Oxane / Nitrosamide / Semicarbazide / Organic n-nitroso compound / Hemiacetal / Carbonic acid derivative / Secondary alcohol
show 13 more
Molecular Framework
Aliphatic heteromonocyclic compounds
External Descriptors
N-nitrosoureas, N-acylglucosamine (CHEBI:9288)

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 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. [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
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. [PubMed:19217614]
Kind
Protein
Organism
Human
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. [PubMed:18721751]

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 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. [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 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. [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 ...
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. [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
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. [PubMed:12065443]

Drug created on June 13, 2005 07:24 / Updated on October 16, 2018 08:26