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pharmacology chemotherapy

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Cytarabine (ARA-C) moa and resistance

Autor: Suzuki



Respuesta:

Cytarabine (cytosine arabinoside) is a pyrimidine antimetabolite. The drug is activated by kinases to AraCTP, an inhibitor of DNA polymerases. Of all the antimetabolites, cytarabine is the most specific for the S phase of the cell cycle. Resistance to cytarabine can occur as a result of its decreased uptake or its decreased conversion to AraCTP. is an analog of 2’-deoxycytidine in which the natural ribose residue is replaced by D-arabinose. Ara-C acts as a pyrimidine antagonist. The major clinical use of ara-C is in acute nonlymphocytic (myelogenous) leukemia in combination with 6-TG and daunorubicin.Ara-C enters the cell by a carrier-mediated process and, like the other purine and pyrimidine antagonists, must be sequentially phosphorylated by deoxycytidine kinase and other nucleotide kinases to the nucleotide form (cytosine arabinoside triphosphate, or ara-CTP ) to be cytotoxic. Ara-CTP is an effective inhibitor of DNA polymerase. The nucleotide is also incorporated into nuclear DNA and can retard chain elongation. It is, therefore,S-phase (and, hence, cell-cycle) specific.


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Suzuki
Suzuki