The Sound of Evolution
Clofarabine
Mechanism of action:
Clofarabine is a purine nucleoside analog. Inside cells, clofarabine is converted into the active metabolite clofarabine triphosphate, which can be mistakenly recognized as deoxyadenosine triphosphate (dATP) and incorporated into DNA. Although clofarabine has a 3'-OH group, its sugar configuration is arabinose, so once incorporated, it often greatly reduces or terminates subsequent DNA elongation. This is related to the poor stereochemical and enzymatic compatibility caused by its arabinose configuration and molecular substituents. It can further inhibit cell division. Clofarabine also inhibits ribonucleotide reductase, thereby blocking the production of dNTPs.
Reference(s):
1. Pession A et al. (2010). Use of clofarabine for acute childhood leukemia. Biologics.
2. Harned TM et al. (2008). Treating refractory leukemias in childhood, role of clofarabine. Ther Clin Risk Manag.
3. Lech-Maranda E et al. (2009). Clofarabine as a novel nucleoside analogue approved to treat patients with haematological malignancies: mechanism of action and clinical activity. Mini Rev Med Chem.