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
Thumb
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.

Pharmacology
Reduce drug development failure rates
Build, train, & validate machine-learning models
with evidence-based and structured datasets.
See how
Build, train, & validate predictive machine-learning models with structured datasets.
See how
Contraindications & Blackbox Warnings
Contraindications
Avoid life-threatening adverse drug events
Improve clinical decision support with information on contraindications & blackbox warnings, population restrictions, harmful risks, & more.
Learn more
Avoid life-threatening adverse drug events & improve clinical decision support.
Learn more
Pharmacodynamics

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.

TargetActionsOrganism
URibonucleoside-diphosphate reductase large subunitNot AvailableHumans
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
Adverseeffects
Improve decision support & research outcomes
With structured adverse effects data, including: blackbox warnings, adverse reactions, warning & precautions, & incidence rates.
Learn more
Improve decision support & research outcomes with our structured adverse effects data.
Learn more
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.
DrugInteraction
Darbepoetin alfaThe risk or severity of Thrombosis can be increased when Darbepoetin alfa is combined with Tezacitabine.
ErythropoietinThe risk or severity of Thrombosis can be increased when Erythropoietin is combined with Tezacitabine.
Methoxy polyethylene glycol-epoetin betaThe risk or severity of Thrombosis can be increased when Methoxy polyethylene glycol-epoetin beta is combined with Tezacitabine.
PeginesatideThe risk or severity of Thrombosis can be increased when Peginesatide is combined with Tezacitabine.
Interactions
Identify potential medication risks
Easily compare up to 40 drugs with our drug interaction checker.
Get severity rating, description, and management advice.
Learn more
Food Interactions
Not Available

Products

Products2
Drug product information from 10+ global regions
Our datasets provide approved product information including:
dosage, form, labeller, route of administration, and marketing period.
Access now
Access drug product information from over 10 global regions.
Access now
Product Ingredients
IngredientUNIICASInChI Key
Tezacitabine monohydrateUCC4EQS7WL171176-43-5XPYQFIISZQCINN-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
PubChem Compound
6435808
ChemSpider
4940503
ChEMBL
CHEMBL2105467
ZINC
ZINC000003777826
Wikipedia
Tezacitabine

Clinical Trials

Clinical Trials
PhaseStatusPurposeConditionsCount
2CompletedTreatmentAdenocarcinomas / Neoplasms, Esophageal / Stomach Neoplasms1
2TerminatedTreatmentNeoplasms, Colorectal1
1CompletedTreatmentMalignancies, Hematologic1

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
PropertyValueSource
Water Solubility3.27 mg/mLALOGPS
logP-1.2ALOGPS
logP-1.9ChemAxon
logS-1.9ALOGPS
pKa (Strongest Acidic)13.28ChemAxon
pKa (Strongest Basic)-0.73ChemAxon
Physiological Charge0ChemAxon
Hydrogen Acceptor Count6ChemAxon
Hydrogen Donor Count3ChemAxon
Polar Surface Area108.38 Å2ChemAxon
Rotatable Bond Count2ChemAxon
Refractivity57.72 m3·mol-1ChemAxon
Polarizability23.05 Å3ChemAxon
Number of Rings2ChemAxon
Bioavailability1ChemAxon
Rule of FiveYesChemAxon
Ghose FilterNoChemAxon
Veber's RuleNoChemAxon
MDDR-like RuleNoChemAxon
Predicted ADMET Features
PropertyValueProbability
Human Intestinal Absorption+1.0
Blood Brain Barrier+0.9746
Caco-2 permeable-0.825
P-glycoprotein substrateNon-substrate0.8055
P-glycoprotein inhibitor INon-inhibitor0.9098
P-glycoprotein inhibitor IINon-inhibitor0.9232
Renal organic cation transporterNon-inhibitor0.9352
CYP450 2C9 substrateNon-substrate0.8513
CYP450 2D6 substrateNon-substrate0.8436
CYP450 3A4 substrateNon-substrate0.5836
CYP450 1A2 substrateNon-inhibitor0.857
CYP450 2C9 inhibitorNon-inhibitor0.8555
CYP450 2D6 inhibitorNon-inhibitor0.8886
CYP450 2C19 inhibitorNon-inhibitor0.8177
CYP450 3A4 inhibitorNon-inhibitor0.9192
CYP450 inhibitory promiscuityLow CYP Inhibitory Promiscuity0.9233
Ames testNon AMES toxic0.7859
CarcinogenicityNon-carcinogens0.8507
BiodegradationNot ready biodegradable0.9503
Rat acute toxicity2.2436 LD50, mol/kg Not applicable
hERG inhibition (predictor I)Weak inhibitor0.9794
hERG inhibition (predictor II)Non-inhibitor0.8621
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

Targets

Drugtargets2
Build, predict & validate machine-learning models
Use our structured and evidence-based datasets to unlock new
insights and accelerate drug research.
Learn more
Use our structured and evidence-based datasets to unlock new insights and accelerate drug research.
Learn more
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
  1. 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
  1. 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