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. View sample adverse effects data in our new Data Library!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 softwareAmbroxol The risk or severity of methemoglobinemia can be increased when Tezacitabine is combined with Ambroxol. Articaine The risk or severity of methemoglobinemia can be increased when Tezacitabine is combined with Articaine. Benzocaine The risk or severity of methemoglobinemia can be increased when Tezacitabine is combined with Benzocaine. Benzyl alcohol The risk or severity of methemoglobinemia can be increased when Tezacitabine is combined with Benzyl alcohol. Bupivacaine The risk or severity of methemoglobinemia can be increased when Tezacitabine is combined with Bupivacaine. - Food Interactions
- Not Available
Products
Drug product information from 10+ global regionsOur datasets provide approved product information including:dosage, form, labeller, route of administration, and marketing period.Access drug product information from over 10 global regions.- Product Ingredients
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 / Esophageal Neoplasms / Neoplasm of Stomach 1 2 Terminated Treatment Colorectal Neoplasms 1 1 Completed Treatment Hematological Malignancy 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) 3.98 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 splash10-00ec-9110000000-1b871148b3083e832bde Predicted MS/MS Spectrum - 10V, Positive (Annotated) Predicted LC-MS/MS splash10-03di-0910000000-bf6e1087dddb4531055e Predicted MS/MS Spectrum - 10V, Negative (Annotated) Predicted LC-MS/MS splash10-0cdi-3590000000-4478c3aafdfc2958ca70 Predicted MS/MS Spectrum - 20V, Positive (Annotated) Predicted LC-MS/MS splash10-03di-0900000000-b2cbc45ebf16de1efb72 Predicted MS/MS Spectrum - 40V, Positive (Annotated) Predicted LC-MS/MS splash10-03di-9850000000-f9cb106257389802f7b8 Predicted MS/MS Spectrum - 20V, Negative (Annotated) Predicted LC-MS/MS splash10-02t9-9850000000-83747bb25f43a9d70b4f Predicted MS/MS Spectrum - 40V, Negative (Annotated) Predicted LC-MS/MS splash10-014l-9200000000-fbf56408cf6f65b3c12f Predicted 1H NMR Spectrum 1D NMR Not Applicable Predicted 13C NMR Spectrum 1D NMR Not Applicable - Chromatographic Properties
Collision Cross Sections (CCS)
Adduct CCS Value (Å2) Source type Source [M-H]- 156.66365 predictedDeepCCS 1.0 (2019) [M+H]+ 159.05922 predictedDeepCCS 1.0 (2019) [M+Na]+ 165.73454 predictedDeepCCS 1.0 (2019)
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 at March 19, 2008 16:33 / Updated at January 14, 2023 19:03