This drug entry is a stub and has not been fully annotated. It is scheduled to be annotated soon.

Identification

Name
Tezacitabine
Accession Number
DB06433
Type
Small Molecule
Groups
Investigational
Description

A synthetic purine nucleoside analogue with potential antineoplastic activity.

Structure
Thumb
Synonyms
  • (E)-2'-deoxy-2'-(fluoromethylene)-cytidine
  • 2'-deoxy-2'-((E)-fluoromethylene)cytidine
  • FMdC
Product Ingredients
IngredientUNIICASInChI Key
Tezacitabine monohydrateUCC4EQS7WL171176-43-5XPYQFIISZQCINN-QVXDJYSKSA-N
Categories
UNII
7607Y95N9S
CAS number
171176-43-5
Weight
Average: 257.2184
Monoisotopic: 257.081184092
Chemical Formula
C10H12FN3O4
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

Pharmacology

Indication

Investigated for use/treatment in colorectal cancer, lung cancer, leukemia (unspecified), and gastric cancer.

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 AvailableHuman
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
Toxicity
Not Available
Affected organisms
  • Humans and other mammals
Pathways
Not Available
Pharmacogenomic Effects/ADRs
Not Available

Interactions

Drug Interactions
DrugInteractionDrug group
AcetyldigitoxinAcetyldigitoxin may decrease the cardiotoxic activities of Tezacitabine.Approved
AcetyldigoxinAcetyldigoxin may decrease the cardiotoxic activities of Tezacitabine.Experimental
AncestimThe risk or severity of cytotoxicity can be increased when Ancestim is combined with Tezacitabine.Approved, Investigational, Withdrawn
BevacizumabBevacizumab may increase the cardiotoxic activities of Tezacitabine.Approved, Investigational
CabazitaxelThe risk or severity of adverse effects can be increased when Cabazitaxel is combined with Tezacitabine.Approved
CyclophosphamideCyclophosphamide may increase the cardiotoxic activities of Tezacitabine.Approved, Investigational
CymarinCymarin may decrease the cardiotoxic activities of Tezacitabine.Experimental
DeslanosideDeslanoside may decrease the cardiotoxic activities of Tezacitabine.Approved
DigitoxinDigitoxin may decrease the cardiotoxic activities of Tezacitabine.Approved, Investigational
DigoxinDigoxin may decrease the cardiotoxic activities of Tezacitabine.Approved
Digoxin Immune Fab (Ovine)Digoxin Immune Fab (Ovine) may decrease the cardiotoxic activities of Tezacitabine.Approved
DocetaxelThe risk or severity of adverse effects can be increased when Docetaxel is combined with Tezacitabine.Approved, Investigational
GitoformateGitoformate may decrease the cardiotoxic activities of Tezacitabine.Experimental
Lanatoside CLanatoside C may decrease the cardiotoxic activities of Tezacitabine.Experimental
MetildigoxinMetildigoxin may decrease the cardiotoxic activities of Tezacitabine.Experimental
OleandrinOleandrin may decrease the cardiotoxic activities of Tezacitabine.Experimental, Investigational
OuabainOuabain may decrease the cardiotoxic activities of Tezacitabine.Approved
PaclitaxelThe risk or severity of adverse effects can be increased when Paclitaxel is combined with Tezacitabine.Approved, Vet Approved
PeruvosidePeruvoside may decrease the cardiotoxic activities of Tezacitabine.Experimental
ProscillaridinProscillaridin may decrease the cardiotoxic activities of Tezacitabine.Experimental
TrastuzumabTrastuzumab may increase the cardiotoxic activities of Tezacitabine.Approved, Investigational
Food Interactions
Not Available

References

General References
Not Available
External Links
PubChem Compound
6435808
ChemSpider
4940503
ChEMBL
CHEMBL2105467
Wikipedia
Tezacitabine

Clinical Trials

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

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

Taxonomy

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
Aminopyrimidine / Pyrimidone / Hydropyrimidine / Imidolactam / Tetrahydrofuran / Heteroaromatic compound / Secondary alcohol / Vinyl fluoride / Vinyl halide / Oxacycle
show 17 more
Molecular Framework
Aromatic heteromonocyclic compounds
External Descriptors
Not Available

Targets

Kind
Protein
Organism
Human
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. [PubMed:10547615]

Enzymes

Kind
Protein
Organism
Human
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. [PubMed:17046720]

Drug created on March 19, 2008 10:33 / Updated on July 02, 2018 20:51