Mechanisms of anti-cancer action and pharmacology of clofarabine.

Article Details

Citation

Zhenchuk A, Lotfi K, Juliusson G, Albertioni F

Mechanisms of anti-cancer action and pharmacology of clofarabine.

Biochem Pharmacol. 2009 Dec 1;78(11):1351-9. doi: 10.1016/j.bcp.2009.06.094. Epub 2009 Jul 1.

PubMed ID
19576186 [ View in PubMed
]
Abstract

Clofarabine, a next-generation deoxyadenosine analogue, was developed on the basis of experience with cladribine and fludarabine in order to achieve higher efficacy and avoid extramedullary toxicity. During the past decade this is the only drug granted approval for treatment of pediatric acute leukemia. Recent clinical studies have established the efficacy of clofarabine in treating malignancies with a poor prognosis, such as adult, elderly, and relapsed pediatric leukemia. The mechanisms of its anti-cancer activity involve a combination of direct inhibition of DNA synthesis and ribonucleotide reductase and induction of apoptosis. Due to this broad cytotoxicity, this drug is effective against various subtypes of leukemia and is currently being tested as an oral formulation and for combination therapy of both leukemias and solid tumors. In this review we summarize current knowledge pertaining to the molecular mechanisms of action and pharmacological properties of clofarabine, as well as clinical experiences with this drug with the purpose of facilitating the evaluation of its efficacy and the development of future therapies.

DrugBank Data that Cites this Article

Drugs
Drug Targets
DrugTargetKindOrganismPharmacological ActionActions
CladribineDNANucleotideHumans
Yes
Other/unknown
Details
CladribineDNA polymerase alpha catalytic subunitProteinHumans
Yes
Inhibitor
Details
CladribineDNA polymerase epsilon catalytic subunit AProteinHumans
Yes
Inhibitor
Details
CladribineDNA polymerase epsilon subunit 2ProteinHumans
Yes
Inhibitor
Details
CladribineDNA polymerase epsilon subunit 3ProteinHumans
Yes
Inhibitor
Details
CladribineDNA polymerase epsilon subunit 4ProteinHumans
Yes
Inhibitor
Details
CladribineRibonucleoside-diphosphate reductase large subunitProteinHumans
Yes
Inhibitor
Details
CladribineRibonucleoside-diphosphate reductase subunit M2ProteinHumans
Yes
Inhibitor
Details
CladribineRibonucleoside-diphosphate reductase subunit M2 BProteinHumans
Yes
Inhibitor
Details
ClofarabineDNA polymerase alpha catalytic subunitProteinHumans
Yes
Inhibitor
Details
ClofarabineRibonucleoside-diphosphate reductase large subunitProteinHumans
Yes
Inhibitor
Details
Drug Enzymes
DrugEnzymeKindOrganismPharmacological ActionActions
CladribineDeoxycytidine kinaseProteinHumans
Unknown
Substrate
Details
ClofarabineDeoxycytidine kinaseProteinHumans
Unknown
Substrate
Details