NAV

Troxacitabine

Identification

Generic Name
Troxacitabine
DrugBank Accession Number
DB04961
Background

Troxacitabine is a nucleoside analog with antineoplastic activity. There has been growing interest in its development for the treatment of patients with refractory lymphoproliferative conditions.

Type
Small Molecule
Groups
Investigational
Structure
3D
Similar Structures
Weight
Average: 213.1906
Monoisotopic: 213.074955855
Chemical Formula
C8H11N3O4
Synonyms
  • (-)-ODDC
  • Troxacitabina
  • Troxacitabine
  • Troxacitabinum
External IDs
  • BCH 4556
  • BCH-4556

Pharmacology

Indication

Investigated for use/treatment in leukemia (myeloid).

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Contraindications & Blackbox Warnings
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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).

TargetActionsOrganism
UDNANot 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
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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
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interactions in your software
AmbroxolThe risk or severity of methemoglobinemia can be increased when Troxacitabine is combined with Ambroxol.
ArticaineThe risk or severity of methemoglobinemia can be increased when Troxacitabine is combined with Articaine.
BenzocaineThe risk or severity of methemoglobinemia can be increased when Troxacitabine is combined with Benzocaine.
Benzyl alcoholThe risk or severity of methemoglobinemia can be increased when Troxacitabine is combined with Benzyl alcohol.
BupivacaineThe risk or severity of methemoglobinemia can be increased when Troxacitabine is combined with Bupivacaine.
ButacaineThe risk or severity of methemoglobinemia can be increased when Troxacitabine is combined with Butacaine.
ButambenThe risk or severity of methemoglobinemia can be increased when Troxacitabine is combined with Butamben.
CapsaicinThe risk or severity of methemoglobinemia can be increased when Troxacitabine is combined with Capsaicin.
ChloroprocaineThe risk or severity of methemoglobinemia can be increased when Troxacitabine is combined with Chloroprocaine.
CinchocaineThe risk or severity of methemoglobinemia can be increased when Troxacitabine is combined with Cinchocaine.
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Food Interactions
Not Available

Products

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International/Other Brands
Troxatyl

Categories

Drug Categories
Chemical TaxonomyProvided by Classyfire
Description
This compound belongs to the class of organic compounds 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.
Kingdom
Organic compounds
Super Class
Nucleosides, nucleotides, and analogues
Class
Nucleoside and nucleotide analogues
Sub Class
Not Available
Direct Parent
Nucleoside and nucleotide analogues
Alternative Parents
Pyrimidones / Aminopyrimidines and derivatives / Imidolactams / Hydropyrimidines / Heteroaromatic compounds / 1,3-dioxolanes / Oxacyclic compounds / Azacyclic compounds / Acetals / Primary amines
show 4 more
Substituents
Acetal / Alcohol / Amine / Aminopyrimidine / Aromatic heteromonocyclic compound / Azacycle / Heteroaromatic compound / Hydrocarbon derivative / Hydropyrimidine / Imidolactam
show 13 more
Molecular Framework
Aromatic heteromonocyclic compounds
External Descriptors
Not Available
Affected organisms
  • Humans and other mammals

Chemical Identifiers

UNII
60KQZ0388Y
CAS number
145918-75-8
InChI Key
RXRGZNYSEHTMHC-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
4-amino-1-[(2S,4S)-2-(hydroxymethyl)-1,3-dioxolan-4-yl]-1,2-dihydropyrimidin-2-one
SMILES
NC1=NC(=O)N(C=C1)[C@@H]1CO[C@H](CO)O1

References

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. [Article]
  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. [Article]
  3. Swords R, Giles F: Troxacitabine in acute leukemia. Hematology. 2007 Jun;12(3):219-27. [Article]
  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. [Article]
  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. [Article]
  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. [Article]
PubChem Compound
454194
PubChem Substance
175426921
ChemSpider
399955
ChEBI
134886
ChEMBL
CHEMBL359164
ZINC
ZINC000001642845
PDBe Ligand
LTT
Wikipedia
Troxacitabine
PDB Entries
2no9

Clinical Trials

Clinical Trials
PhaseStatusPurposeConditionsCount
2CompletedTreatmentLeukemias1
2TerminatedTreatmentAcute Myeloid Leukemia1
1, 2TerminatedTreatmentAcute Myeloid Leukemia1
1, 2TerminatedTreatmentNeoplasm1

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 Solubility14.8 mg/mLALOGPS
logP-1.7ALOGPS
logP-1.3Chemaxon
logS-1.2ALOGPS
pKa (Strongest Acidic)13.85Chemaxon
pKa (Strongest Basic)4.22Chemaxon
Physiological Charge0Chemaxon
Hydrogen Acceptor Count6Chemaxon
Hydrogen Donor Count2Chemaxon
Polar Surface Area97.38 Å2Chemaxon
Rotatable Bond Count2Chemaxon
Refractivity48.73 m3·mol-1Chemaxon
Polarizability19.54 Å3Chemaxon
Number of Rings2Chemaxon
Bioavailability1Chemaxon
Rule of FiveYesChemaxon
Ghose FilterNoChemaxon
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
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

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Details1. DNA
Kind
Nucleotide
Organism
Humans
Pharmacological action
Unknown
DNA is the molecule of heredity, as it is responsible for the genetic propagation of most inherited traits. It is a polynucleic acid that carries genetic information on cell growth, division, and function. DNA consists of two long strands of nucleotides twisted into a double helix and held together by hydrogen bonds. The sequence of nucleotides determines hereditary characteristics. Each strand serves as the template for subsequent DNA replication and as a template for mRNA production, leading to protein synthesis via ribosomes.
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. [Article]

Enzymes

Details1. Deoxycytidine kinase
Kind
Protein
Organism
Humans
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...
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. [Article]
  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. [Article]

Drug created at October 21, 2007 22:23 / Updated at January 14, 2023 19:03