Tezacitabine
This drug entry is a stub and has not been fully annotated. It is scheduled to be annotated soon.
Identification
- Generic Name
- Tezacitabine
- DrugBank Accession Number
- DB06433
- Background
A synthetic purine nucleoside analogue with potential antineoplastic activity.
- Type
- Small Molecule
- Groups
- Investigational
- Structure
Structure for Tezacitabine (DB06433)
- Weight
- Average: 257.2184
Monoisotopic: 257.081184092 - Chemical Formula
- C10H12FN3O4
- Synonyms
- 2'-Deoxy-2'-(fluoromethylene)cytidine
- Tezacitabine
- External IDs
- KW-2331
- MDL 101,731
- MDL 101731
Pharmacology
- Indication
Investigated for use/treatment in colorectal cancer, lung cancer, leukemia (unspecified), and gastric cancer.
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Not Available
- Mechanism of action
Phosphorylated by cellular kinases, tezacitabine is converted into its active diphosphate and triphosphate metabolites. Tezacitabine diphosphate binds to and irreversibly inhibits the activity of the enzyme ribonucleotide reductase (RNR), which may result in the inhibition of DNA synthesis in tumor cells and tumor cell apoptosis. Tezacitabine triphosphate acts as a substrate for DNA polymerase, further compromising DNA replication. This agent is relatively resistant to metabolic deactivation by cytidine deaminase. RNR catalyzes the conversion of ribonucleoside 5'-diphosphates to deoxyribonucleoside 5'-diphosphates necessary for DNA synthesis and is overexpressed in many tumor types.
Target Actions Organism URibonucleoside-diphosphate reductase large subunit Not Available Humans - Absorption
Not Available
- Volume of distribution
Not Available
- Protein binding
Not Available
- Metabolism
- Not Available
- Route of elimination
Not Available
- Half-life
Not Available
- Clearance
Not Available
- Adverse Effects
Improve decision support & research outcomesWith structured adverse effects data, including: blackbox warnings, adverse reactions, warning & precautions, & incidence rates.Improve decision support & research outcomes with our structured adverse effects data.- Toxicity
Not Available
- 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.
Drug Interaction Integrate drug-drug
interactions in your softwareDarbepoetin alfa The risk or severity of Thrombosis can be increased when Darbepoetin alfa is combined with Tezacitabine. Erythropoietin The risk or severity of Thrombosis can be increased when Erythropoietin is combined with Tezacitabine. Methoxy polyethylene glycol-epoetin beta The risk or severity of Thrombosis can be increased when Methoxy polyethylene glycol-epoetin beta is combined with Tezacitabine. Peginesatide The risk or severity of Thrombosis can be increased when Peginesatide is combined with Tezacitabine. 
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- Not Available
Products
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Ingredient UNII CAS InChI Key Tezacitabine monohydrate UCC4EQS7WL 171176-43-5 XPYQFIISZQCINN-QVXDJYSKSA-N
Categories
- Drug Categories
- Chemical TaxonomyProvided by Classyfire
- Description
- This compound belongs to the class of organic compounds known as pyrimidones. These are compounds that contain a pyrimidine ring, which bears a ketone. Pyrimidine is a 6-membered ring consisting of four carbon atoms and two nitrogen centers at the 1- and 3- ring positions.
- Kingdom
- Organic compounds
- Super Class
- Organoheterocyclic compounds
- Class
- Diazines
- Sub Class
- Pyrimidines and pyrimidine derivatives
- Direct Parent
- Pyrimidones
- Alternative Parents
- Aminopyrimidines and derivatives / Hydropyrimidines / Imidolactams / Tetrahydrofurans / Heteroaromatic compounds / Secondary alcohols / Vinyl fluorides / Azacyclic compounds / Oxacyclic compounds / Fluoroalkenes show 6 more
- Substituents
- Alcohol / Amine / Aminopyrimidine / Aromatic heteromonocyclic compound / Azacycle / Fluoroalkene / Haloalkene / Heteroaromatic compound / Hydrocarbon derivative / Hydropyrimidine show 17 more
- Molecular Framework
- Aromatic heteromonocyclic compounds
- External Descriptors
- Not Available
- Affected organisms
- Humans and other mammals
Chemical Identifiers
- UNII
- 7607Y95N9S
- CAS number
- 171176-43-5
- InChI Key
- GFFXZLZWLOBBLO-ASKVSEFXSA-N
- InChI
- InChI=1S/C10H12FN3O4/c11-3-5-8(16)6(4-15)18-9(5)14-2-1-7(12)13-10(14)17/h1-3,6,8-9,15-16H,4H2,(H2,12,13,17)/b5-3+/t6-,8+,9-/m1/s1
- IUPAC Name
- 4-amino-1-[(2R,3E,4S,5R)-3-(fluoromethylidene)-4-hydroxy-5-(hydroxymethyl)oxolan-2-yl]-1,2-dihydropyrimidin-2-one
- SMILES
- NC1=NC(=O)N(C=C1)[C@@H]1O[C@H](CO)[C@@H](O)\C1=C/F
References
- General References
- Not Available
- External Links
- PubChem Compound
- 6435808
- ChemSpider
- 4940503
- ChEMBL
- CHEMBL2105467
- ZINC
- ZINC000003777826
- Wikipedia
- Tezacitabine
Clinical Trials
- Clinical Trials
Phase Status Purpose Conditions Count 2 Completed Treatment Adenocarcinomas / Neoplasms, Esophageal / Stomach Neoplasms 1 2 Terminated Treatment Neoplasms, Colorectal 1 1 Completed Treatment Malignancies, Hematologic 1
Pharmacoeconomics
- Manufacturers
- Not Available
- Packagers
- Not Available
- Dosage Forms
- Not Available
- Prices
- Not Available
- Patents
- Not Available
Properties
- State
- Solid
- Experimental Properties
- Not Available
- Predicted Properties
Property Value Source Water Solubility 3.27 mg/mL ALOGPS logP -1.2 ALOGPS logP -1.9 ChemAxon logS -1.9 ALOGPS pKa (Strongest Acidic) 13.28 ChemAxon pKa (Strongest Basic) -0.73 ChemAxon Physiological Charge 0 ChemAxon Hydrogen Acceptor Count 6 ChemAxon Hydrogen Donor Count 3 ChemAxon Polar Surface Area 108.38 Å2 ChemAxon Rotatable Bond Count 2 ChemAxon Refractivity 57.72 m3·mol-1 ChemAxon Polarizability 23.05 Å3 ChemAxon Number of Rings 2 ChemAxon Bioavailability 1 ChemAxon Rule of Five Yes ChemAxon Ghose Filter No ChemAxon Veber's Rule No ChemAxon MDDR-like Rule No ChemAxon - Predicted ADMET Features
Property Value Probability Human Intestinal Absorption + 1.0 Blood Brain Barrier + 0.9746 Caco-2 permeable - 0.825 P-glycoprotein substrate Non-substrate 0.8055 P-glycoprotein inhibitor I Non-inhibitor 0.9098 P-glycoprotein inhibitor II Non-inhibitor 0.9232 Renal organic cation transporter Non-inhibitor 0.9352 CYP450 2C9 substrate Non-substrate 0.8513 CYP450 2D6 substrate Non-substrate 0.8436 CYP450 3A4 substrate Non-substrate 0.5836 CYP450 1A2 substrate Non-inhibitor 0.857 CYP450 2C9 inhibitor Non-inhibitor 0.8555 CYP450 2D6 inhibitor Non-inhibitor 0.8886 CYP450 2C19 inhibitor Non-inhibitor 0.8177 CYP450 3A4 inhibitor Non-inhibitor 0.9192 CYP450 inhibitory promiscuity Low CYP Inhibitory Promiscuity 0.9233 Ames test Non AMES toxic 0.7859 Carcinogenicity Non-carcinogens 0.8507 Biodegradation Not ready biodegradable 0.9503 Rat acute toxicity 2.2436 LD50, mol/kg Not applicable hERG inhibition (predictor I) Weak inhibitor 0.9794 hERG inhibition (predictor II) Non-inhibitor 0.8621
Spectra
- Mass Spec (NIST)
- Not Available
- Spectra
Spectrum Spectrum Type Splash Key Predicted GC-MS Spectrum - GC-MS Predicted GC-MS Not Available Predicted MS/MS Spectrum - 10V, Positive (Annotated) Predicted LC-MS/MS Not Available Predicted MS/MS Spectrum - 20V, Positive (Annotated) Predicted LC-MS/MS Not Available Predicted MS/MS Spectrum - 40V, Positive (Annotated) Predicted LC-MS/MS Not Available Predicted MS/MS Spectrum - 10V, Negative (Annotated) Predicted LC-MS/MS Not Available Predicted MS/MS Spectrum - 20V, Negative (Annotated) Predicted LC-MS/MS Not Available Predicted MS/MS Spectrum - 40V, Negative (Annotated) Predicted LC-MS/MS Not Available
Targets
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- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- Unknown
- General Function
- Ribonucleoside-diphosphate reductase activity, thioredoxin disulfide as acceptor
- Specific Function
- Provides the precursors necessary for DNA synthesis. Catalyzes the biosynthesis of deoxyribonucleotides from the corresponding ribonucleotides.
- Gene Name
- RRM1
- Uniprot ID
- P23921
- Uniprot Name
- Ribonucleoside-diphosphate reductase large subunit
- Molecular Weight
- 90069.375 Da
References
- Skierski JS, Koronkiewicz M, Grieb P: Effect of FMdC on the cell cycle of some leukemia cell lines. Cytometry. 1999 Dec 1;37(4):302-7. [Article]
Enzymes
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- Unknown
- Actions
- Inducer
- General Function
- Transferase activity, transferring pentosyl groups
- Specific Function
- May have a role in maintaining the integrity of the blood vessels. Has growth promoting activity on endothelial cells, angiogenic activity in vivo and chemotactic activity on endothelial cells in v...
- Gene Name
- TYMP
- Uniprot ID
- P19971
- Uniprot Name
- Thymidine phosphorylase
- Molecular Weight
- 49954.965 Da
References
- Taverna P, Rendahl K, Jekic-McMullen D, Shao Y, Aardalen K, Salangsang F, Doyle L, Moler E, Hibner B: Tezacitabine enhances the DNA-directed effects of fluoropyrimidines in human colon cancer cells and tumor xenografts. Biochem Pharmacol. 2007 Jan 1;73(1):44-55. Epub 2006 Sep 16. [Article]
Drug created on March 19, 2008 16:33 / Updated on February 21, 2021 18:52