title: 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.affiliation: Department of Biomedical Chemistry, Medical University of Łódź, 6/8 Mazowiecka St., 92-215 Łódź, Poland.
authors.forename: Katarzyna
authors.initials: K
authors.lastname: Majda
authors.forename: Katarzyna
authors.initials: K
authors.lastname: Lubecka
authors.forename: Agnieszka
authors.initials: A
authors.lastname: Kaufman-Szymczyk
authors.forename: Krystyna
authors.initials: K
authors.lastname: Fabianowska-Majewska
mesh_terms: D000227:Adenine Nucleotides / Q000737:chemistry / Q000493:pharmacokinetics / Q000494:pharmacology* / Q000627:therapeutic use; D000328:Adult; D000818:Animals; D000970:Antineoplastic Agents / Q000737:chemistry / Q000493:pharmacokinetics / Q000494:pharmacology* / Q000627:therapeutic use; D017209:Apoptosis / Q000187:drug effects; D001087:Arabinonucleosides / Q000737:chemistry / Q000493:pharmacokinetics / Q000494:pharmacology* / Q000627:therapeutic use; D001711:Biotransformation; D002648:Child; D000077866:Clofarabine; D004261:DNA Replication / Q000187:drug effects; D044127:Epigenesis, Genetic / Q000187:drug effects; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects; D006801:Humans; D015394:Molecular Structure; D054198:Precursor Cell Lymphoblastic Leukemia-Lymphoma / Q000188:drug therapy / Q000235:genetics / Q000473:pathology; D013329:Structure-Activity Relationship
chemical_list: D000227:Adenine Nucleotides; D000970:Antineoplastic Agents; D001087:Arabinonucleosides; D000077866:Clofarabine