Clofarabine (2-chloro-2'-fluoro-2'-deoxyarabinosyladenine)--biochemical aspects of anticancer activity.

Abstract

Clofarabine (2-chloro-2'-fluoro-2'-deoxyarabinosyladenine) is a second generation analogue of 2'-deoxyadenosine connecting biochemical activities of its prototypes: cladribine (2-chloro-2'-deoxyadenosine) and fludarabine (2-fluoro-arabinosyladenine). This new anticancer drug is more effective (in low doses) and indicates higher oral bioavailability in comparison to its congeners. The studies indicated that the molecular mechanism of clofarabine cytotoxic action includes cell apoptosis, which results from inhibition (by the drug triphosphate nucleotides) of ribonucleotide reductase and DNA polymerases. The most recent research demonstrated also that action of the drug may cause up-expression of some genes on mRNA and protein levels. Clofarabine was synthesized in 1992 and in 2004 was approved for treatment of pediatric patients with refractory or relapsed acute lymphoblastic leukemia (ALL). Encouraging results of clinical trials with clofarabine in acute leukemias inclined to present background knowledge about multidirectional biomolecular mechanism of its cytotoxicity.

• Authors: Katarzyna Majda, Katarzyna Lubecka, Agnieszka Kaufman-Szymczyk, Krystyna Fabianowska-Majewska
• Journal: Acta poloniae pharmaceutica (Acta Pol Pharm) 2011 Jul-Aug Vol. 68 Issue 4 Pg. 459-66 ISSN: 0001-6837 [Print] Poland
• PMID: 21796927 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't, Review)

Chemical References

• Adenine Nucleotides
• Antineoplastic Agents
• Arabinonucleosides
• Clofarabine

Topics

• Adenine Nucleotides (chemistry, pharmacokinetics, pharmacology, therapeutic use)
• Adult
• Animals
• Antineoplastic Agents (chemistry, pharmacokinetics, pharmacology, therapeutic use)
• Apoptosis (drug effects)
• Arabinonucleosides (chemistry, pharmacokinetics, pharmacology, therapeutic use)
• Biotransformation
• Child
• Clofarabine
• DNA Replication (drug effects)
• Epigenesis, Genetic (drug effects)
• Gene Expression Regulation, Neoplastic (drug effects)
• Humans
• Molecular Structure
• Precursor Cell Lymphoblastic Leukemia-Lymphoma (drug therapy, genetics, pathology)
• Structure-Activity Relationship