Clofarabine

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Scientific Name: Clofarabine
Brand Name: Clolar, Evoltra
Company Owner: Genzyme corp
Mechanism Of Action 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.
Description of the Drug: Clofarabine is a purine nucleoside used to treat relapsed or refractory acute lymphoblastic leukemia in patients 1 to 21 years old.
Protein Data Bank:
Source: DrugBank Online – DrugBank.com. Retrieved 2023-01-23 from https://go.drugbank.com/drugs/DB00631