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Clofarabine DNA/RNA Synthesis inhibitor

Name: Clofarabine
Brand: Selleck Chemicals
SKU: S1218
Availability: InStock
Rating: 5 (23 reviews)

Cat.No.S1218

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

Chemical Structure

Molecular Weight: 303.68

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Quality Control

Batch: Purity: 99.90%

99.90

Related Targets	HDAC PARP ATM/ATR DNA-PK WRN Topoisomerase PPAR Sirtuin Casein Kinase eIF
Other DNA/RNA Synthesis Inhibitors	B02 CX-5461 (Pidnarulex) SCR7 EED226 Favipiravir (T-705) RK-33 Carmofur Triapine (3-AP) BMH-21 YK-4-279

Cell Culture, Treatment & Working Concentration

Cell Lines	Assay Type	Concentration	Incubation Time	Activity Description	PMID
K562 cell	Cytotoxicity assay			Compound was tested for cytotoxicity against K562 cell lines, IC50=0.003 μM	1732556
HEp-2 cell	Cytotoxicity assay			Compound was tested for cytotoxicity against HEp-2 cell lines, IC50=0.012 μM	1732556
CCRF-CEM cell lines	Cytotoxicity assay			Compound was tested for cytotoxicity against CCRF-CEM cell lines, IC50=0.05 μM	1732556
L1210 cell	Cytotoxicity assay			Compound was tested for cytotoxicity against L1210 cell lines, IC50=2.3 μM	1732556
NCI-H23	Cytotoxicity assay		5 days	Cytotoxicity against human NCI-H23 cells after 5 days by SRB assay, GI50=0.04μM	19929004
PC3	Cytotoxicity assay		5 days	Cytotoxicity against human PC3 cells after 5 days by SRB assay, GI50=0.063μM	19929004
BT549	Cytotoxicity assay		5 days	Cytotoxicity against human BT549 cells after 5 days by SRB assay, GI50=0.065μM	19929004
HCT15	Cytotoxicity assay		5 days	Cytotoxicity against human HCT15 cells after 5 days by SRB assay, GI50=0.18μM	19929004
NCI-H23	Cytostatic assay		5 days	Cytostatic activity against human NCI-H23 cells after 5 days by SRB assay, GI50=0.04μM	21711054
MT4	Cytostatic assay		5 days	Cytostatic activity against human MT4 cells after 5 days by SRB assay, GI50=0.051μM	21711054
PC3	Cytostatic assay		5 days	Cytostatic activity against human PC3 cells after 5 days by SRB assay, GI50=0.063μM	21711054
BT549	Cytostatic assay		5 days	Cytostatic activity against human BT549 cells after 5 days by SRB assay, GI50=0.065μM	21711054
A549	Cytostatic assay		5 days	Cytostatic activity against human A549 cells after 5 days by SRB assay, GI50=0.086μM	21711054
HCT116	Cytostatic assay		5 days	Cytostatic activity against human HCT116 cells after 5 days by SRB assay, GI50=0.106μM	21711054
DU145	Cytostatic assay		5 days	Cytostatic activity against human DU145 cells after 5 days by SRB assay, GI50=0.125μM	21711054
HCT15	Cytostatic assay		5 days	Cytostatic activity against human HCT15 cells after 5 days by SRB assay, GI50=0.18μM	21711054
Hs578	Cytostatic assay		5 days	Cytostatic activity against human Hs578 cells after 5 days by SRB assay, GI50=1.241μM	21711054
HL60	Cytostatic assay		48 hrs	Cytostatic activity against human HL60 cells after 48 hrs by MTT assay, IC50=0.1μM	23820572
A549	Cytostatic assay		48 hrs	Cytostatic activity against human A549 cells after 48 hrs by MTT assay, IC50=8μM	23820572
U373-MAGI	Function assay	50 nM	2 hrs	Potentiation of 5-Aza-C-induced antiviral activity against VSV-G pseudotyped HIV-1 NL4-3 infected in human U373-MAGI cells assessed as 5-Aza-C EC50 at 50 nM preincubated for 2 hrs followed by 5-Aza-C addition for 2 hrs and subsequent viral infection measu, EC50=30.4μM	27117260
U373-MAGI	Antiviral assay	50 nM	4 hrs	Antiviral activity against VSV-G pseudotyped HIV-1 NL4-3 infected in human U373-MAGI cells assessed as reduction in viral infectivity at 50 nM incubated for 4 hrs prior to viral infection measured at 72 hrs post infection by flow cytometric analysis	27117260
U373-MAGI	Function assay	200 nM	6 hrs	Reduction in dGTP level in human U373-MAGI cells at 200 nM after 6 hrs by LC-MS/MS analysis	27117260
U373-MAGI	Function assay	200 nM	6 hrs	Reduction in dCTP level in human U373-MAGI cells at 200 nM after 6 hrs by LC-MS/MS analysis	27117260
U373-MAGI	Function assay	200 nM	6 hrs	Reduction in dATP level in human U373-MAGI cells at 200 nM after 6 hrs by LC-MS/MS analysis	27117260
U373-MAGI	Function assay	50 nM	2 hrs	Reduction in dCTP level in human U373-MAGI cells at 50 nM preincubated for 2 hrs followed by 5-aza-C addition measured after 4 hrs by LC-MS/MS analysis	27117260
U373-MAGI	Function assay	200 nM	2 hrs	Reduction in dCTP level in human U373-MAGI cells at 200 nM preincubated for 2 hrs followed by 5-aza-C addition measured after 4 hrs by LC-MS/MS analysis relative to 5-aza-C	27117260
U373-MAGI	Function assay	50 nM	2 hrs	Increase in 5-aza-dCTP/dCTP ratio in human U373-MAGI cells at 50 nM preincubated for 2 hrs followed by 5-aza-dC addition measured after 4 hrs by LC-MS/MS analysis relative to 5-aza-dC	27117260
U373-MAGI	Function assay	200 nM	2 hrs	Increase in 5-aza-dCTP/dCTP ratio in human U373-MAGI cells at 200 nM preincubated for 2 hrs followed by 5-aza-dC addition measured after 4 hrs by LC-MS/MS analysis relative to 5-aza-dC	27117260
U373-MAGI	Function assay	200 nM	2 hrs	Reduction in dRGU-TP level in human U373-MAGI cells at 200 nM preincubated for 2 hrs followed by 5-aza-C addition measured after 4 hrs by LC-MS/MS analysis	27117260
U373-MAGI	Function assay	200 nM	2 hrs	Reduction in 5-aza-dCTP level in human U373-MAGI cells at 200 nM preincubated for 2 hrs followed by 5-aza-C addition measured after 4 hrs by LC-MS/MS analysis	27117260
U373-MAGI	Function assay	200 nM	2 hrs	Reduction in dCTP level in human U373-MAGI cells at 200 nM preincubated for 2 hrs followed by 5-aza-dC addition measured after 4 hrs by LC-MS/MS analysis relative to 5-aza-dC	27117260
U373-MAGI	Function assay	50 nM	2 hrs	Reduction in dCTP level in human U373-MAGI cells at 50 nM preincubated for 2 hrs followed by 5-aza-dC addition measured after 4 hrs by LC-MS/MS analysis relative to 5-aza-dC	27117260
TC32	qHTS assay			qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Primary screen for TC32 cells	29435139
DAOY	qHTS assay			qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Primary screen for DAOY cells	29435139
SJ-GBM2	qHTS assay			qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Primary screen for SJ-GBM2 cells	29435139
A673	qHTS assay			qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Primary screen for A673 cells	29435139
SK-N-MC	qHTS assay			qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Primary screen for SK-N-MC cells	29435139
BT-37	qHTS assay			qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Primary screen for BT-37 cells	29435139
NB-EBc1	qHTS assay			qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Primary screen for NB-EBc1 cells	29435139
LAN-5	qHTS assay			qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Primary screen for LAN-5 cells	29435139
OHS-50	qHTS assay			qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Primary screen for OHS-50 cells	29435139
MG 63 (6-TG R)	qHTS assay			qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Primary screen for MG 63 (6-TG R) cells	29435139
NB1643	qHTS assay			qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Confirmatory screen for NB1643 cells	29435139
A673	qHTS assay			qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Confirmatory screen for A673 cells)	29435139
SK-N-MC	qHTS assay			qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Confirmatory screen for SK-N-MC cells	29435139
LAN-5	qHTS assay			qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Confirmatory screen for LAN-5 cells	29435139
SJ-GBM2	qHTS assay			qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Confirmatory screen for SJ-GBM2 cells	29435139
BT-37	qHTS assay			qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Confirmatory screen for BT-37 cells	29435139
TC32	qHTS assay			qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Confirmatory screen for TC32 cells	29435139
MG 63 (6-TG R)	qHTS assay			qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Confirmatory screen for MG 63 (6-TG R) cells	29435139
Rh30	qHTS assay			qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Confirmatory screen for Rh30 cells	29435139
Saos-2	qHTS assay			qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Confirmatory screen for Saos-2 cells	29435139
SJ-GBM2	qHTS assay			qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Orthogonal 3D viability screen for SJ-GBM2 cells	29435139
TC32	qHTS assay			qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Orthogonal 3D viability screen for TC32 cells	29435139
MG 63 (6-TG R)	qHTS assay			qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Orthogonal 3D viability screen for MG 63 (6-TG R) cells	29435139
Granta	Cytotoxicity assay		72 hrs	Cytotoxicity against human Granta cells assessed as decrease in cell viability after 72 hrs by MTT assay, IC50=0.017μM	30176535
HL60	Cytotoxicity assay		72 hrs	Cytotoxicity against human HL60 cells assessed as decrease in cell viability after 72 hrs by MTT assay, IC50=0.04μM	30176535
CCRF-CEM	Cytotoxicity assay		72 hrs	Cytotoxicity against human CCRF-CEM cells assessed as decrease in cell viability after 72 hrs by MTT assay, IC50=0.044μM	30176535
RL	Cytotoxicity assay		72 hrs	Cytotoxicity against human RL cells assessed as decrease in cell viability after 72 hrs by MTT assay, IC50=0.38μM	30176535
Click to View More Cell Line Experimental Data

Solubility

In vitro
Batch:

DMSO : 60 mg/mL (197.57 mM)
(Moisture-contaminated DMSO may reduce solubility. Use fresh, anhydrous DMSO.)

Water : Insoluble

Ethanol : Insoluble

Molarity Calculator

Mass	Concentration	Volume	Molecular Weight
Mass value Mass unit	Concentration value Concentration unit	Volume value Volume unit	Molecular weight (g/mol)

Dilution Calculator Molecular Weight Calculator

In vivo batch selection In vivo Batch:
Homogeneous suspension	CMC-NA	≥5mg/ml	Taking the 1 mL working solution as an example, add 5 mg of this product to 1 ml of CMC-Na solution, mix evenly to obtain a homogeneous suspension with a final concentration of 5 mg/ml.
Homogeneous suspension	CMC-NA	≥5mg/ml	Taking the 1 mL working solution as an example, add 5 mg of this product to 1 ml of CMC-Na solution, mix evenly to obtain a homogeneous suspension with a final concentration of 5 mg/ml.
Homogeneous suspension	CMC-NA	≥5mg/ml	Taking the 1 mL working solution as an example, add 5 mg of this product to 1 ml of CMC-Na solution, mix evenly to obtain a homogeneous suspension with a final concentration of 5 mg/ml.
Homogeneous suspension	CMC-NA	≥5mg/ml	Taking the 1 mL working solution as an example, add 5 mg of this product to 1 ml of CMC-Na solution, mix evenly to obtain a homogeneous suspension with a final concentration of 5 mg/ml.
Homogeneous suspension	CMC-NA	≥5mg/ml	Taking the 1 mL working solution as an example, add 5 mg of this product to 1 ml of CMC-Na solution, mix evenly to obtain a homogeneous suspension with a final concentration of 5 mg/ml.

In vivo Formulation Calculator (Clear solution)

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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.

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Chemical Information, Storage & Stability

Molecular Weight	303.68	Formula	C₁₀H₁₁ClFN₅O₃	Storage (From the date of receipt)	3 years-20°Cpowder
CAS No.	123318-82-1	Download SDF		Storage of Stock Solutions	1 year-80°Cin solvent 1 month-20°Cin solvent
Synonyms	Clolar			Smiles	C1=NC2=C(N=C(N=C2N1C3C(C(C(O3)CO)O)F)Cl)N

Mechanism of Action

Targets/IC₅₀/Ki	Ribonucleotide reductase (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. This compound 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. This compound triphosphate is a potent inhibitor of ribonucleotide reductase (IC50 = 65 nM), presumably by binding to the allosteric site on the regulatory subunit. It 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. This chemical 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. It 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. This compound (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. It (10 μM) combined with 4-hydroperoxycyclophosphamide (4-HC) produces more than additive apoptotic cell death than the sum of each alone. This chemical (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.
References	[1] https://pubmed.ncbi.nlm.nih.gov/17016426/ [2] https://pubmed.ncbi.nlm.nih.gov/11705880/ [3] https://pubmed.ncbi.nlm.nih.gov/15723262/

Clinical Trial Information

(data from https://clinicaltrials.gov, updated on 2024-05-22)

NCT Number	Recruitment	Conditions	Sponsor/Collaborators	Start Date	Phases
NCT05917405	Recruiting	Acute Myeloid Leukemia in Remission	Nantes University Hospital	September 14 2023	Phase 2
NCT03609814	Completed	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	--

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