Identification
NameTroxacitabine
Accession NumberDB04961
TypeSmall Molecule
GroupsInvestigational
Description

Troxacitabine (brand name Troxatyl) is a nucleoside analogue with anticancer activity. Its use is being studied in patients with refractory lymphoproliferative diseases.

Structure
Thumb
Synonyms
(-)-ODDC
External IDs BCH-4556
Product Ingredients Not Available
Approved Prescription ProductsNot Available
Approved Generic Prescription ProductsNot Available
Approved Over the Counter ProductsNot Available
Unapproved/Other Products Not Available
International Brands
NameCompany
TroxatylNot Available
Brand mixturesNot Available
Categories
UNII60KQZ0388Y
CAS number145918-75-8
WeightAverage: 213.1906
Monoisotopic: 213.074955855
Chemical FormulaC8H11N3O4
InChI KeyRXRGZNYSEHTMHC-BQBZGAKWSA-N
InChI
InChI=1S/C8H11N3O4/c9-5-1-2-11(8(13)10-5)6-4-14-7(3-12)15-6/h1-2,6-7,12H,3-4H2,(H2,9,10,13)/t6-,7-/m0/s1
IUPAC Name
1-[(2S,4S)-2-(hydroxymethyl)-1,3-dioxolan-4-yl]-4-imino-1,4-dihydropyrimidin-2-ol
SMILES
[H][[email protected]]1(CO)OC[[email protected]]([H])(O1)N1C=CC(=N)N=C1O
Pharmacology
Indication

Investigated for use/treatment in leukemia (myeloid).

Structured Indications Not Available
Pharmacodynamics

Troxacitabine is a beta-L-nucleoside analog, which has shown preclinical antitumor activity in human xenograft tumor models and antileukemic response in patients with relapsed myeloid leukemia.

Mechanism of action

Troxacitabine is activated by cellular kinases and incorporated into DNA, inhibiting its replication. In contrast to other cytosine nucleoside analogs, troxacitabine is resistant to inactivation by cytidine deaminase (CD).

TargetKindPharmacological actionActionsOrganismUniProt ID
DNANucleotideunknownNot AvailableHumannot applicabledetails
Related Articles
AbsorptionNot Available
Volume of distributionNot Available
Protein bindingNot Available
MetabolismNot Available
Route of eliminationNot Available
Half lifeNot Available
ClearanceNot Available
ToxicityNot Available
Affected organisms
  • Humans and other mammals
PathwaysNot Available
Pharmacogenomic Effects/ADRs Not Available
Interactions
Drug Interactions
DrugInteractionDrug group
AcetyldigitoxinAcetyldigitoxin may decrease the cardiotoxic activities of Troxacitabine.Approved
BevacizumabBevacizumab may increase the cardiotoxic activities of Troxacitabine.Approved, Investigational
CabazitaxelThe risk or severity of adverse effects can be increased when Cabazitaxel is combined with Troxacitabine.Approved
CyclophosphamideCyclophosphamide may increase the cardiotoxic activities of Troxacitabine.Approved, Investigational
DeslanosideDeslanoside may decrease the cardiotoxic activities of Troxacitabine.Approved
DigitoxinDigitoxin may decrease the cardiotoxic activities of Troxacitabine.Approved
DigoxinDigoxin may decrease the cardiotoxic activities of Troxacitabine.Approved
DocetaxelThe risk or severity of adverse effects can be increased when Docetaxel is combined with Troxacitabine.Approved, Investigational
OleandrinAnvirzel may decrease the cardiotoxic activities of Troxacitabine.Experimental
OuabainOuabain may decrease the cardiotoxic activities of Troxacitabine.Approved
PaclitaxelThe risk or severity of adverse effects can be increased when Paclitaxel is combined with Troxacitabine.Approved, Vet Approved
TrastuzumabTrastuzumab may increase the cardiotoxic activities of Troxacitabine.Approved, Investigational
Food InteractionsNot Available
References
Synthesis ReferenceNot Available
General References
  1. Lee CK, Rowinsky EK, Li J, Giles F, Moore MJ, Hidalgo M, Capparelli E, Jolivet J, Baker SD: Population pharmacokinetics of troxacitabine, a novel dioxolane nucleoside analogue. Clin Cancer Res. 2006 Apr 1;12(7 Pt 1):2158-65. [PubMed:16609029 ]
  2. Quintas-Cardama A, Cortes J: Evaluation of the L-stereoisomeric nucleoside analog troxacitabine for the treatment of acute myeloid leukemia. Expert Opin Investig Drugs. 2007 Apr;16(4):547-57. [PubMed:17371201 ]
  3. Swords R, Giles F: Troxacitabine in acute leukemia. Hematology. 2007 Jun;12(3):219-27. [PubMed:17558697 ]
  4. Orsolic N, Giles FJ, Gourdeau H, Golemovic M, Beran M, Cortes J, Freireich EJ, Kantarjian H, Verstovsek S: Troxacitabine and imatinib mesylate combination therapy of chronic myeloid leukaemia: preclinical evaluation. Br J Haematol. 2004 Mar;124(6):727-38. [PubMed:15009060 ]
  5. Boivin AJ, Gourdeau H, Momparler RL: Action of troxacitabine on cells transduced with human cytidine deaminase cDNA. Cancer Invest. 2004;22(1):25-9. [PubMed:15069761 ]
  6. Kim TE, Park SY, Hsu CH, Dutschman GE, Cheng YC: Synergistic antitumor activity of troxacitabine and camptothecin in selected human cancer cell lines. Mol Pharmacol. 2004 Aug;66(2):285-92. [PubMed:15266019 ]
External Links
ATC CodesNot Available
AHFS CodesNot Available
PDB EntriesNot Available
FDA labelNot Available
MSDSNot Available
Clinical Trials
Clinical Trials
PhaseStatusPurposeConditionsCount
1, 2TerminatedTreatmentAcute Myelogenous Leukaemia (AML)1
1, 2TerminatedTreatmentNeoplasms1
2CompletedTreatmentLeukemias1
2TerminatedTreatmentLeukemia, Myeloid, Acute1
Pharmacoeconomics
ManufacturersNot Available
PackagersNot Available
Dosage formsNot Available
PricesNot Available
PatentsNot Available
Properties
StateSolid
Experimental PropertiesNot Available
Predicted Properties
PropertyValueSource
Water Solubility1.83 mg/mLALOGPS
logP-1.4ALOGPS
logP-0.34ChemAxon
logS-2.1ALOGPS
pKa (Strongest Acidic)9.15ChemAxon
pKa (Strongest Basic)2.43ChemAxon
Physiological Charge0ChemAxon
Hydrogen Acceptor Count7ChemAxon
Hydrogen Donor Count3ChemAxon
Polar Surface Area98.37 Å2ChemAxon
Rotatable Bond Count2ChemAxon
Refractivity60.14 m3·mol-1ChemAxon
Polarizability19.94 Å3ChemAxon
Number of Rings2ChemAxon
Bioavailability1ChemAxon
Rule of FiveYesChemAxon
Ghose FilterYesChemAxon
Veber's RuleNoChemAxon
MDDR-like RuleNoChemAxon
Predicted ADMET features
PropertyValueProbability
Human Intestinal Absorption+0.9521
Blood Brain Barrier+0.9127
Caco-2 permeable-0.8297
P-glycoprotein substrateNon-substrate0.7729
P-glycoprotein inhibitor INon-inhibitor0.9677
P-glycoprotein inhibitor IINon-inhibitor0.9795
Renal organic cation transporterNon-inhibitor0.9024
CYP450 2C9 substrateNon-substrate0.7935
CYP450 2D6 substrateNon-substrate0.8712
CYP450 3A4 substrateNon-substrate0.6202
CYP450 1A2 substrateNon-inhibitor0.9331
CYP450 2C9 inhibitorNon-inhibitor0.9296
CYP450 2D6 inhibitorNon-inhibitor0.9337
CYP450 2C19 inhibitorNon-inhibitor0.9226
CYP450 3A4 inhibitorNon-inhibitor0.9018
CYP450 inhibitory promiscuityLow CYP Inhibitory Promiscuity0.9516
Ames testNon AMES toxic0.5127
CarcinogenicityNon-carcinogens0.8646
BiodegradationNot ready biodegradable0.9301
Rat acute toxicity1.9792 LD50, mol/kg Not applicable
hERG inhibition (predictor I)Weak inhibitor0.9671
hERG inhibition (predictor II)Non-inhibitor0.9287
ADMET data is predicted using admetSAR, a free tool for evaluating chemical ADMET properties. (23092397 )
Spectra
Mass Spec (NIST)Not Available
Spectra
Spectrum TypeDescriptionSplash Key
Predicted GC-MSPredicted GC-MS Spectrum - GC-MSNot Available
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 10V, PositiveNot Available
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 20V, PositiveNot Available
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 40V, PositiveNot Available
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 10V, NegativeNot Available
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 20V, NegativeNot Available
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 40V, NegativeNot Available
Taxonomy
DescriptionThis compound belongs to the class of chemical entities known as nucleoside and nucleotide analogues. These are analogues of nucleosides and nucleotides. These include phosphonated nucleosides, C-glycosylated nucleoside bases, analogues where the sugar unit is a pyranose, and carbocyclic nucleosides, among others.
KingdomChemical entities
Super ClassOrganic compounds
ClassNucleosides, nucleotides, and analogues
Sub ClassNucleoside and nucleotide analogues
Direct ParentNucleoside and nucleotide analogues
Alternative ParentsPyrimidones / Aminopyrimidines and derivatives / Primary aromatic amines / Imidolactams / Hydropyrimidines / Heteroaromatic compounds / 1,3-dioxolanes / Oxacyclic compounds / Azacyclic compounds / Acetals
SubstituentsAminopyrimidine / Pyrimidone / Hydropyrimidine / Primary aromatic amine / Pyrimidine / Imidolactam / Heteroaromatic compound / Meta-dioxolane / Oxacycle / Azacycle
Molecular FrameworkAromatic heteromonocyclic compounds
External DescriptorsNot Available

Targets

1. DNA
Kind
Nucleotide
Organism
Human
Pharmacological action
unknown
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. Boivin AJ, Gourdeau H, Momparler RL: Action of troxacitabine on cells transduced with human cytidine deaminase cDNA. Cancer Invest. 2004;22(1):25-9. [PubMed:15069761 ]

Enzymes

Kind
Protein
Organism
Human
Pharmacological action
unknown
Actions
activator
General Function:
Protein homodimerization activity
Specific Function:
Required for the phosphorylation of the deoxyribonucleosides deoxycytidine (dC), deoxyguanosine (dG) and deoxyadenosine (dA). Has broad substrate specificity, and does not display selectivity based on the chirality of the substrate. It is also an essential enzyme for the phosphorylation of numerous nucleoside analogs widely employed as antiviral and chemotherapeutic agents.
Gene Name:
DCK
Uniprot ID:
P27707
Uniprot Name:
Deoxycytidine kinase
Molecular Weight:
30518.315 Da
References
  1. Adema AD, Zuurbier L, Floor K, Hubeek I, Kaspers GJ, Albertoni F, Peters GJ: Cellular resistance against troxacitabine in human cell lines and pediatric patient acute myeloid leukemia blast cells. Nucleosides Nucleotides Nucleic Acids. 2006;25(9-11):981-6. [PubMed:17065050 ]
  2. Adema AD, Radi M, Daft J, Narayanasamy J, Hoebe EK, Alexander LE, Chu CK, Peters GJ: Troxacitabine prodrugs for pancreatic cancer. Nucleosides Nucleotides Nucleic Acids. 2007;26(8-9):1073-7. [PubMed:18058539 ]
Drug created on October 21, 2007 16:23 / Updated on September 01, 2017 11:23