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DOT/IATA TRANSPORT INFORMATION
UN #:
UN2811
Hazard Class:
6.1; Poison
Packing Group:
III
A hazmat fee may apply to certain package sizes and shipment methods. Please check pricing table for an indicator of applicable hazmat fees.
BIOLOGICAL INFO
Solubility:
DMSO: 61mg/mL; H2O: <1mg/mL; EtOH: <1mg/mL
Application(s):
Inhibits the enzymatic activities of ribonucleotide reductase and DNA polymerase
Form:
Free Base
REVIEW Clofarabine is metabolized intracellularly to the active 5''-monophosphate metabolite by deoxycytidine kinase and 5''-triphosphate metabolite by mono- and di-phospho-kinases. This metabolite inhibits DNA synthesis through an inhibitory action on ribonucleotide reductase, and by terminating DNA chain elongation and inhibiting repair through competitive inhibition of DNA polymerases. This leads to the depletion of the intracellular deoxynucleotide triphosphate pool and the self-potentiation of clofarabine triphosphate incorporation into DNA, thereby intensifying the effectiveness of DNA synthesis inhibition. The affinity of clofarabine triphosphate for these enzymes is similar to or greater than that of deoxyadenosine triphosphate. In preclinical models, clofarabine has demonstrated the ability to inhibit DNA repair by incorporation into the DNA chain during the repair process. Clofarabine 5''-triphosphate also disrupts the integrity of mitochondrial membrane, leading to the release of the pro-apoptotic mitochondrial proteins, cytochrome C and apoptosis-inducing factor, leading to programmed cell death.
REFERENCES
[1]
Pession A, Masetti R, Kleinschmidt K, Martoni A: Use of clofarabine for acute childhood leukemia. Biologics. 2010 Jun 24;4:111-8.
[2]
Harned TM, Gaynon PS: Treating refractory leukemias in childhood, role of clofarabine. Ther Clin Risk Manag. 2008 Apr;4(2):327-36.
[3]
Lech-Maranda E, Korycka A, Robak T: Clofarabine as a novel nucleoside analogue approved to treat patients with haematological malignancies: mechanism of action and clinical activity. Mini Rev Med Chem. 2009 Jun;9(7):805-12.
[4]
Larson ML, Venugopal P: Clofarabine: a new treatment option for patients with acute myeloid leukemia. Expert Opin Pharmacother. 2009 Jun;10(8):1353-7.
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