Clofarabine

Catalog No.S1218 Synonyms: Clolar

For research use only.

Clofarabine (Clolar) inhibits the enzymatic activities of ribonucleotide reductase (RNR) (IC50 = 65 nM) and DNA polymerase. Clofarabine induces autophagy and apoptosis.

Clofarabine Chemical Structure

CAS No. 123318-82-1

Selleck's Clofarabine has been cited by 14 publications

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Biological Activity

Description Clofarabine (Clolar) inhibits the enzymatic activities of ribonucleotide reductase (RNR) (IC50 = 65 nM) and DNA polymerase. Clofarabine induces autophagy and apoptosis.
Targets
Ribonucleotide reductase [1]
(Cell-free assay)
65 nM
In vitro

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. [1] 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. [2] Clofarabine (1 μM) combined with ara-C (10 μM) results in a biochemical modulation of ara-CTP and synergistic cell kill in K562 cells. [3]

Cell Data
Cell Lines Assay Type Concentration Incubation Time Formulation Activity Description PMID
K562 cell M{nNVWN6fG:2b4jpZ4l1gSCjc4PhfS=> MnrhR49ueG:3bnSge4F{KHSnc4Tl[EBnd3JiY4n0c5RwgGmlaYT5JIFo[Wmwc4SgT|U3OiClZXzsJIxqdmW|LDDJR|UxRTBwMECzJO69VQ>? NHzoWHA9[SC2YYLn[ZQ:L1:kbHHub{chcHKnZk2nbJR1eHN8Lz;weYJu\WRwbnPibU5vdG1wbnnoModwfi9zN{OyOVU3Lz5zN{OyOVU3RC:jPh?=
HEp-2 cell NGLKeolEgXSxdH;4bYNqfHliYYPzZZk> NX;seWZXS2:vcH;1coQhf2G|IITld5Rm\CCob4KgZ5l1d3SxeHnjbZR6KGGpYXnud5QhUEWyLUKgZ4VtdCCuaX7ld{whUUN3ME2wMlAyOiEQvF2= M3exeFxiKHSjcnfleF0oZ2KuYX7rK{BpemWoPTfoeJRxezpxL4D1Zo1m\C6wY3LpMo5tdS6waXiu[493NzF5M{K1OVYoRjF5M{K1OVY9N2F-
CCRF-CEM cell lines MUjDfZRwfG:6aXPpeJkh[XO|YYm= MonpR49ueG:3bnSge4F{KHSnc4Tl[EBnd3JiY4n0c5RwgGmlaYT5JIFo[Wmwc4SgR2NTTi2FRV2gZ4VtdCCuaX7ld{whUUN3ME2wMlA2KM7:TR?= MYe8ZUB1[XKpZYS9K39jdGGwazegbJJm\j1paIT0dJM7Ny:ydXLt[YQvdmOkaT7ucI0vdmmqLnfvek8yPzN{NUW2K|4yPzN{NUW2QE9iRg>?
L1210 cell M4Tnd2N6fG:2b4jpZ4l1gSCjc4PhfS=> NGSzU5lEd22yb4Xu[EB4[XNidHXzeIVlKG[xcjDjfZRwfG:6aXPpeJkh[WejaX7zeEBNOTJzMDDj[YxtKGyrbnXzMEBKSzVyPUKuN{DPxE1? NIW4N|c9[SC2YYLn[ZQ:L1:kbHHub{chcHKnZk2nbJR1eHN8Lz;weYJu\WRwbnPibU5vdG1wbnnoModwfi9zN{OyOVU3Lz5zN{OyOVU3RC:jPh?=
NCI-H23 M3HUc2N6fG:2b4jpZ4l1gSCjc4PhfS=> MW[1JIRigXN? NEPiRWJEgXSxdH;4bYNqfHliYXfhbY5{fCCqdX3hckBPS0lvSEKzJINmdGy|IHHmeIVzKDViZHH5d{BjgSCVUlKgZZN{[XluIFfJOVA:OC5yNN88US=> MYO8ZUB1[XKpZYS9K39jdGGwazegbJJm\j1paIT0dJM7Ny:ydXLt[YQvdmOkaT7ucI0vdmmqLnfvek8yQTl{OUCwOEc,OTl7MkmwNFQ9N2F-
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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. [1]

Protocol (from reference)

Solubility (25°C)

In vitro

DMSO 60 mg/mL
(197.57 mM)
Water Insoluble
Ethanol Insoluble

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.

8mg/mL

* Please note that Selleck tests the solubility of all compounds in-house, and the actual solubility may differ slightly from published values. This is normal and is due to slight batch-to-batch variations.

Chemical Information

Molecular Weight 303.68
Formula

C10H11ClFN5O3

CAS No. 123318-82-1
Storage 3 years -20°C powder
2 years -80°C in solvent
Smiles C1=NC2=C(N=C(N=C2N1C3C(C(C(O3)CO)O)F)Cl)N

In vivo Formulation Calculator (Clear solution)

Step 1: Enter information below (Recommended: An additional animal making an allowance for loss during the experiment)

mg/kg g μL

Step 2: Enter the in vivo formulation (This is only the calculator, not formulation. Please contact us first if there is no in vivo formulation at the solubility Section.)

% DMSO % % Tween 80 % ddH2O
%DMSO %

Calculation results:

Working concentration: mg/ml;

Method for preparing DMSO master liquid: mg drug pre-dissolved in μL DMSO ( Master liquid concentration mg/mL, Please contact us first if the concentration exceeds the DMSO solubility of the batch of drug. )

Method for preparing in vivo formulation: Take μL DMSO master liquid, next addμL PEG300, mix and clarify, next addμL Tween 80, mix and clarify, next add μL ddH2O, mix and clarify.

Method for preparing in vivo formulation: Take μL DMSO master liquid, next add μL Corn oil, mix and clarify.

Note: 1. Please make sure the liquid is clear before adding the next solvent.
2. Be sure to add the solvent(s) in order. You must ensure that the solution obtained, in the previous addition, is a clear solution before proceeding to add the next solvent. Physical methods such
as vortex, ultrasound or hot water bath can be used to aid dissolving.

Molarity Calculator

Mass Concentration Volume Molecular Weight

Clinical Trial Information

NCT Number Recruitment Interventions Conditions Sponsor/Collaborators Start Date Phases
NCT03609814 Completed Drug: Clofarabine|Drug: Fludarabine Injection Hematologic Malignancies|Nonmalignant Diseases|Immunodeficiencies|Hemoglobinopathies|Genetic Inborn Errors of Metabolism|Fanconi''s Anemia|Thalassemia|Sickle Cell Disease University of California San Francisco January 26 2016 --
NCT02425904 Active not 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

(data from https://clinicaltrials.gov, updated on 2022-01-17)

Tech Support

Answers to questions you may have can be found in the inhibitor handling instructions. Topics include how to prepare stock solutions, how to store inhibitors, and issues that need special attention for cell-based assays and animal experiments.

Handling Instructions

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