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Clolar (CLOFARABINE)

Sanofi · FDA-approved approved Small molecule Verified Quality 70/100

Clolar works by inhibiting the enzyme responsible for DNA synthesis, thereby preventing cancer cells from reproducing.

Clolar (clofarabine) is a nucleoside metabolic inhibitor developed by Genzyme, targeting ribonucleoside-diphosphate reductase large subunit. It is a small molecule modality approved by the FDA in 2004 for the treatment of acute lymphoid leukemia. Clolar is now off-patent with 12 generic manufacturers available. The drug has a half-life of 4.0 hours and 50% bioavailability. It is used to treat a specific type of blood cancer.

At a glance

Generic nameCLOFARABINE
SponsorSanofi
Drug classNucleoside Metabolic Inhibitor [EPC]
TargetRibonucleoside-diphosphate reductase large subunit
ModalitySmall molecule
Therapeutic areaOncology
PhaseFDA-approved
First approval2004

Mechanism of action

Clofarabine is sequentially metabolized intracellularly to the 5-monophosphate metabolite by deoxycytidine kinase and mono- and di-phospho-kinases to the active 5-triphosphate metabolite. Clofarabine has affinity for the activating phosphorylating enzyme, deoxycytidine kinase, equal to or greater than that of the natural substrate, deoxycytidine. Clofarabine inhibits DNA synthesis by decreasing cellular deoxynucleotide triphosphate pools through an inhibitory action on ribonucleotide reductase, and by terminating DNA chain elongation and inhibiting repair through incorporation into the DNA chain by competitive inhibition of DNA polymerases. 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 integr

Approved indications

Common side effects

Key clinical trials

Primary sources

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SourceUsed for
FDA labelMechanism, indications, dosing, boxed warnings, drug interactions
ClinicalTrials.govTrial enrolment, design, endpoints, results

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