Molecular Weight(MW): 303.68
Clofarabine inhibits the enzymatic activities of ribonucleotide reductase (IC50 = 65 nM) and DNA polymerase.
Cited by 6 Publications
2 Customer Reviews
Immunoblot analysis of cell lysates of NCI-H929 cells treated with CLO (5 μM, 3-48 h) GAPDH served as the loading control for each membrane, and data are representative of at least two independent experiments
Clin Cancer Res, 2017, 23(17):5225-5237. Clofarabine purchased from Selleck.
Population-based pharmacokinetic modeling of plasma pharmacokinetic study and cerebral microdialysis study. Representative individual plasma and/or tumor ECF concentration-time profile of unbound clofarabine from plasma pharmacokinetic study (a) and cerebral microdialysis study (b) (open circles and triangles represent observed clofarabine unbound plasma and tumor ECF concentrations, respectively; Dotted and solid lines represent model-predicted individual unbound plasma and tumor ECF concentrations, respectively). Box plot comparison of individual volume of peripheral compartment (c) and systemic clearance (d) between plasma pharmacokinetic study (45 mg/kg clofarabine) and cerebral microdialysis study (30 mg/kg clofarabine).
Cancer Chemoth Pharm, 2015, 75:897-906.. Clofarabine purchased from Selleck.
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Choose Selective DNA/RNA Synthesis Inhibitors
|Description||Clofarabine inhibits the enzymatic activities of ribonucleotide reductase (IC50 = 65 nM) and DNA polymerase.|
Clofarabine is efficiently transported into cells via two facilitative or equilibrative nucleoside transporters, hENT1 and hENT2, and a concentrative nucleoside transporter, hCNT253. Clofarabine is phosphorylated in a stepwise manner by cytosolic kinases to the nucleotide analogues clofarabine 5′-mono-, di- and triphosphate following entry into cells, with Clofarabine triphosphate being the active form. Clofarabine 5′-mono-, di- and triphosphate are not substrates for nucleoside transporters and must be enzymatically converted by 5′-nucleotidase back to their dephosphorylated nucleoside form for transport out of the cell. Clofarabine triphosphate is a potent inhibitor of ribonucleotide reductase (IC50 = 65 nM), presumably by binding to the allosteric site on the regulatory subunit. Clofarabine has also been shown to act directly on mitochondria by altering the transmembrane potential with release of cytochrome c, apoptotic-inducing factor (AIF), apoptosis protease-activating factor 1 (APAF1) and caspase 9 into the cytosol. Clofarabine demonstrates strong in vitro growth inhibition and cytotoxic activity (IC50 values = 0.028–0.29 μM) in a wide variety of leukaemia and solid tumour cell lines. Clofarabine has been shown to increase the activity of dCK in HL60 cells, and increases the formation of the mono-, di-, and triphosphates of ara-C in K562 cells36.  Clofarabine (10 μM) inhibits the repair initiated by 4-hydroperoxycyclophosphamide (4-HC), with inhibition peaking at the intracellular concentrations of 5 μM in chronic lymphocytic leukemia (CLL) lymphocytes. Clofarabine (10 μM) combined with 4-hydroperoxycyclophosphamide (4-HC) produces more than additive apoptotic cell death than the sum of each alone.  Clofarabine (1 μM) combined with ara-C (10 μM) results in a biochemical modulation of ara-CTP and synergistic cell kill in K562 cells. 
|In vivo||Clofarabine administered intraperitoneally has significant activity against a wide variety of human tumour xenografts implanted subcutaneously in athymic nude or severe combined immune deficiency mice. |
|In vitro||DMSO||60 mg/mL (197.57 mM)|
|In vivo||Add solvents to the product individually and in order(Data is from Selleck tests instead of citations):
2% DMSO+30% PEG 300 +1% Tween 80+ddH2O
For best results, use promptly after mixing.
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Clinical Trial Information
|NCT Number||Recruitment||interventions||Conditions||Sponsor/Collaborators||Start Date||Phases|
|NCT03609814||Recruiting||--||Hematologic Malignancies|Nonmalignant Diseases|Immunodeficiencies|Hemoglobinopathies|Genetic Inborn Errors of Metabolism|Fanconi''s Anemia|Thalassemia|Sickle Cell Disease||University of California San Francisco||February 2016||--|
|NCT02425904||Recruiting||Drug: Clofarabine||Langerhans Cell Histiocytosis||Dana-Farber Cancer Institute|Sanofi|St. Baldrick''s Foundation|Cookies for Kids'' Cancer|North American Consortium for Histiocytosis||May 2015||Phase 2|
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