CLOFARABINE

Details

Stereochemistry	ABSOLUTE
Molecular Formula	C10H11ClFN5O3
Molecular Weight	303.677
Optical Activity	UNSPECIFIED
Defined Stereocenters	4 / 4
E/Z Centers	0
Charge	0

SHOW SMILES / InChI

Structure Search

SMILES

NC1=NC(Cl)=NC2=C1N=CN2[C@@H]3O[C@H](CO)[C@@H](O)[C@@H]3F

InChI

InChIKey=WDDPHFBMKLOVOX-AYQXTPAHSA-N

InChI=1S/C10H11ClFN5O3/c11-10-15-7(13)5-8(16-10)17(2-14-5)9-4(12)6(19)3(1-18)20-9/h2-4,6,9,18-19H,1H2,(H2,13,15,16)/t3-,4+,6-,9-/m1/s1

HIDE SMILES / InChI

Molecular Formula	C10H11ClFN5O3
Molecular Weight	303.677
Charge	0
Count

Stereochemistry	ABSOLUTE
Additional Stereochemistry	No
Defined Stereocenters	4 / 4
E/Z Centers	0
Optical Activity	UNSPECIFIED

Description
Sources: https://www.ncbi.nlm.nih.gov/pubmed/22840768
Curator's Comment: description was created based on several sources, including http://www.accessdata.fda.gov/drugsatfda_docs/label/2015/021673s024lbl.pdf

Clofarabine is a anti-cancer drug which was approved by FDA for the treatment of pediatric patients with relapsed or refractory acute lymphoblastic leukemia. After crossing the cell membrane the drug is rapidly metabolized by deoxycytidine kinase to diphosphate and triphosphate metabolites and these metabolites reversibly inhibit hRNR by binding to alpha subunit. Also the triphosphate is incorporated to DNA where it acts as a chain terminator.

CNS Activity

Originator

Approval Year

Targets

Primary Target	Pharmacology	Condition	Potency
DNA 282 Target ID: CHEMBL2311221 Sources: http://www.accessdata.fda.gov/drugsatfda_docs/label/2015/021673s024lbl.pdf	Binding Agent 1076
Ribonucleoside-diphosphate reductase RR1 14 Target ID: CHEMBL2095215 Sources: http://www.accessdata.fda.gov/drugsatfda_docs/label/2015/021673s024lbl.pdf	Inhibitor 8504		17.0 nM [Ki]

Conditions

Condition	Modality	Targets	Highest Phase	Product
Relapsed or refractory acute lymphoblastic leukemia 2 Sources: http://www.accessdata.fda.gov/drugsatfda_docs/label/2015/021673s024lbl.pdf	Primary		Approved 8583	CLOLAR Approved Use Clolar® (clofarabine) Injection is indicated for the treatment of pediatric patients 1 to 21 years old with relapsed or refractory acute lymphoblastic leukemia after at least two prior regimens. Launch Date 2004

C_max

Value	Dose	Co-administered	Analyte	Population
308 ng/mL EXPERIMENT https://www.ncbi.nlm.nih.gov/pubmed/28509593	40 mg/m² 1 times / day multiple, intravenous dose: 40 mg/m² route of administration: Intravenous experiment type: MULTIPLE co-administered: CYTARABINE	CYTARABINE	CLOFARABINE plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN
598.8 ng/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/27086352/	52 mg/m² 1 times / day multiple, intravenous dose: 52 mg/m² route of administration: Intravenous experiment type: MULTIPLE co-administered:		CLOFARABINE plasma	Homo sapiens population: UNHEALTHY age: CHILD sex: FEMALE / MALE food status:
683.5 ng/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/27086352/	52 mg/m² single, intravenous dose: 52 mg/m² route of administration: Intravenous experiment type: SINGLE co-administered:		CLOFARABINE plasma	Homo sapiens population: UNHEALTHY age: CHILD sex: FEMALE / MALE food status:

AUC

Value	Dose	Co-administered	Analyte	Population
1793 ng × h/mL EXPERIMENT https://www.ncbi.nlm.nih.gov/pubmed/28509593	40 mg/m² 1 times / day multiple, intravenous dose: 40 mg/m² route of administration: Intravenous experiment type: MULTIPLE co-administered: CYTARABINE	CYTARABINE	CLOFARABINE plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN
28 ng × h/mL EXPERIMENT https://www.ncbi.nlm.nih.gov/pubmed/29773602	40 mg/m² 1 times / day multiple, intravenous dose: 40 mg/m² route of administration: Intravenous experiment type: MULTIPLE co-administered:		CLOFARABINE blood	Homo sapiens population: UNHEALTHY age: CHILD sex: UNKNOWN food status: UNKNOWN
1462.8 ng × h/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/27086352/	52 mg/m² 1 times / day multiple, intravenous dose: 52 mg/m² route of administration: Intravenous experiment type: MULTIPLE co-administered:		CLOFARABINE plasma	Homo sapiens population: UNHEALTHY age: CHILD sex: FEMALE / MALE food status:
2358.2 ng × h/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/27086352/	52 mg/m² single, intravenous dose: 52 mg/m² route of administration: Intravenous experiment type: SINGLE co-administered:		CLOFARABINE plasma	Homo sapiens population: UNHEALTHY age: CHILD sex: FEMALE / MALE food status:

T_1/2

Value	Dose	Co-administered	Analyte	Population
4.9 h EXPERIMENT https://www.ncbi.nlm.nih.gov/pubmed/28509593	40 mg/m² 1 times / day multiple, intravenous dose: 40 mg/m² route of administration: Intravenous experiment type: MULTIPLE co-administered: CYTARABINE	CYTARABINE	CLOFARABINE plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN
1.5 h EXPERIMENT https://www.ncbi.nlm.nih.gov/pubmed/29773602	40 mg/m² 1 times / day multiple, intravenous dose: 40 mg/m² route of administration: Intravenous experiment type: MULTIPLE co-administered:		CLOFARABINE blood	Homo sapiens population: UNHEALTHY age: CHILD sex: UNKNOWN food status: UNKNOWN
1.977 h EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/27086352/	52 mg/m² 1 times / day multiple, intravenous dose: 52 mg/m² route of administration: Intravenous experiment type: MULTIPLE co-administered:		CLOFARABINE plasma	Homo sapiens population: UNHEALTHY age: CHILD sex: FEMALE / MALE food status:
3.933 h EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/27086352/	52 mg/m² single, intravenous dose: 52 mg/m² route of administration: Intravenous experiment type: SINGLE co-administered:		CLOFARABINE plasma	Homo sapiens population: UNHEALTHY age: CHILD sex: FEMALE / MALE food status:

Doses

Dose	Population	Adverse events
55 mg/m2 1 times / day multiple, intravenous Highest studied dose Dose: 55 mg/m2, 1 times / day Route: intravenous Route: multiple Dose: 55 mg/m2, 1 times / day Sources: https://pubmed.ncbi.nlm.nih.gov/12637486	unhealthy, 42 years Health Status: unhealthy Age Group: 42 years Sex: M+F Sources: https://pubmed.ncbi.nlm.nih.gov/12637486	Other AEs: Nausea, Diarrhea... Other AEs: Nausea (grade 1-2, 2 patients) Diarrhea (grade 1, 3 patients) Hepatotoxicity (grade 3, 2 patients) Sources: https://pubmed.ncbi.nlm.nih.gov/12637486
40 mg/m2 1 times / day multiple, intravenous MTD Dose: 40 mg/m2, 1 times / day Route: intravenous Route: multiple Dose: 40 mg/m2, 1 times / day Sources: https://pubmed.ncbi.nlm.nih.gov/12637486	unhealthy, 42 years Health Status: unhealthy Age Group: 42 years Sex: M+F Sources: https://pubmed.ncbi.nlm.nih.gov/12637486	Other AEs: Nausea, Fatigue... Other AEs: Nausea (grade 1-2, 3 patients) Fatigue (grade 3, 1 patient) Diarrhea (grade 1, 2 patients) Cramp (grade 1, 1 patient) Anorexia (grade 1, 1 patient) Mucositis (grade 1, 1 patient) Edema (grade 1, 1 patient) Hepatotoxicity (grade 3-4, 4 patients) Sources: https://pubmed.ncbi.nlm.nih.gov/12637486
2 mg/m2 1 times / day multiple, intravenous MTD Dose: 2 mg/m2, 1 times / day Route: intravenous Route: multiple Dose: 2 mg/m2, 1 times / day Sources: https://pubmed.ncbi.nlm.nih.gov/12637486	unhealthy, 51 years Health Status: unhealthy Age Group: 51 years Sex: M+F Sources: https://pubmed.ncbi.nlm.nih.gov/12637486	DLT: Myelosuppression... Dose limiting toxicities: Myelosuppression (grade 3, 2 patients) Sources: https://pubmed.ncbi.nlm.nih.gov/12637486
6 mg 1 times / day multiple, oral Highest studied dose Dose: 6 mg, 1 times / day Route: oral Route: multiple Dose: 6 mg, 1 times / day Sources: https://pubmed.ncbi.nlm.nih.gov/24415560	unhealthy, 60-76 years Health Status: unhealthy Age Group: 60-76 years Sources: https://pubmed.ncbi.nlm.nih.gov/24415560	Other AEs: Nausea, Hypoalbuminemia... Other AEs: Nausea (grade 1-2, 1 patient) Hypoalbuminemia (grade 1-2, 1 patient) Blood bilirubin decreased (grade 1-2, 1 patient) Lymphopenia (grade 3-4) Sources: https://pubmed.ncbi.nlm.nih.gov/24415560
70 mg/m2 1 times / day multiple, intravenous Highest studied dose Dose: 70 mg/m2, 1 times / day Route: intravenous Route: multiple Dose: 70 mg/m2, 1 times / day Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2004/021673lbl.pdf	unhealthy, child Health Status: unhealthy Age Group: child Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2004/021673lbl.pdf	Other AEs: Hyperbilirubinemia, Vomiting... Other AEs: Hyperbilirubinemia (grade 4, 2 patients) Vomiting (grade 2-3, 2 patients) Maculopapular rash (grade 3, 2 patients) Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2004/021673lbl.pdf

AEs

Overview

CYP3A4	CYP2C9	CYP2D6	hERG
			inhibitor 2217

OverviewOther

Other Inhibitor	Other Substrate	Other Inducer
	CYP450 59

Drug as victim

Target	Modality	Activity	Metabolite	Clinical evidence
CYP450 59	substrate 4014 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2004/21-673_Clolar_biopharmr.PDF#page=18 Page: 18.0	no

Tox targets

Target	Modality	Activity	Metabolite	Clinical evidence
hERG 2263	inhibitor 2237 Sources: https://www.pharmadoor.com.br/images/medicamentos/bulas/clolar_bula.pdf#page=30 Page: 30.0

Sourcing

Vendor/Aggregator	ID	URL
ChEBI	CHEBI:681569	https://www.ebi.ac.uk/chebi/searchId.do?chebiId=CHEBI:681569
eMolecules	29256989	https://www.emolecules.com/cgi-bin/more?vid=29256989
eMolecules	30512527	https://www.emolecules.com/cgi-bin/more?vid=30512527
MolPort	MolPort-005-941-711	https://www.molport.com/shop/molecule-link/MolPort-005-941-711
Selleck Chemicals	Clofarabine	http://www.selleckchem.com/products/Clofarabine.html
ZINC	ZINC000003798247	http://zinc15.docking.org/substances/ZINC000003798247

PubMed

Title	Date	PubMed
Enhancement of the in vivo antitumor activity of clofarabine by 1-beta-D-[4-thio-arabinofuranosyl]-cytosine.	2009-07	19002461
Clofarabine in refractory Langerhans cell histiocytosis.	2008-11	18623218
Clofarabine: in search of combinations for the treatment of patients with high-risk acute myeloid leukemia.	2008-10-15	18780321
Clofarabine combinations as acute myeloid leukemia salvage therapy.	2008-10-15	18756533
Polyadenylation inhibition by the triphosphates of deoxyadenosine analogues.	2008-10	18433867
A randomized study of clofarabine versus clofarabine plus low-dose cytarabine as front-line therapy for patients aged 60 years and older with acute myeloid leukemia and high-risk myelodysplastic syndrome.	2008-09-01	18565853
Contribution of the drug transporter ABCG2 (breast cancer resistance protein) to resistance against anticancer nucleosides.	2008-09	18765824
Synthetic studies on formamidopyrimidines related to clofarabine.	2008-08	18696361
New drugs in acute myeloid leukemia.	2008-08	18692694
Acute myeloid leukemia in the elderly.	2008-08	18692693
Acute myeloid leukemia in the elderly: conventional and novel treatment approaches.	2008-07	18433953
Novel purine nucleoside analogues for hematological malignancies.	2008-06	18537755
Cytotoxic activities of nucleoside and nucleobase analog drugs in malignant mesothelioma: characterization of a novel nucleobase transport activity.	2008-05-15	18371936
Fatal skin and liver toxicity in a patient treated with clofarabine.	2008-05	17957757
Treating refractory leukemias in childhood, role of clofarabine.	2008-04	18728851
Potential role of novel nucleoside analogs in the treatment of acute myeloid leukemia.	2008-03	18300755
Clofarabine acts as radiosensitizer in vitro and in vivo by interfering with DNA damage response.	2008-01-01	18037589
Cytotoxic nucleoside analogues: different strategies to improve their clinical efficacy.	2008	18473803
The combination of clofarabine and cytarabine in pediatric relapsed acute lymphoblastic leukemia: a case report.	2008	18303261
Clofarabine: new drug. Children with acute lymphoblastic leukaemia: a last resort.	2007-12	18092403
Three new drugs for acute lymphoblastic leukemia: nelarabine, clofarabine, and forodesine.	2007-12	18086342
Pharmacogenetics of deoxycytidine kinase: identification and characterization of novel genetic variants.	2007-12	17855478
Clofarabine: past, present, and future.	2007-10	17852710
A phase 1 clinical-laboratory study of clofarabine followed by cyclophosphamide for adults with refractory acute leukemias.	2007-09-15	17562873
Clofarabine induced durable complete remission in heavily pretreated adolescents with relapsed and refractory leukemia.	2007-09	17805046
Saccharomyces cerevisiae emboli in an immunocompromised patient with relapsed acute myeloid leukaemia.	2007-07	17376213
Comparison of fast liquid chromatography/tandem mass spectrometric methods for simultaneous determination of cladribine and clofarabine in mouse plasma.	2007-06-28	17368998
Cell cycle effect on the activity of deoxynucleoside analogue metabolising enzymes.	2007-06-15	17459340
In vitro cytotoxicity of nelarabine, clofarabine and flavopiridol in paediatric acute lymphoblastic leukaemia.	2007-04	17391490
Advances in the management of AML in the elderly.	2007-03	17519879
Clofarabine for the treatment of acute lymphoblastic leukemia.	2007-02	17288522
Efficacy of low dose clofarabine in refractory precursor T- acute lymphoblastic leukemia.	2006-12	17940627
Nursing considerations for clofarabine in the treatment of acute lymphoblastic leukemia in children.	2006-12	17193947
Gateways to clinical trials.	2006-11	17200730
The activity and toxicity of low dose clofarabine against relapsed or refractory myeloma.	2006-11	17043015
Clofarabine and nelarabine: two new purine nucleoside analogs.	2006-11	16988579
Gateways to clinical trials.	2006-10	17136234
New directions in the treatment of mantle cell lymphoma: an overview.	2006-10	17101070
A tale of two drugs.	2006-10	17078168
Discovery and development of clofarabine: a nucleoside analogue for treating cancer.	2006-10	17016426
Clinical and pharmacokinetic study of clofarabine in chronic lymphocytic leukemia: strategy for treatment.	2006-07-01	16818700
Pharmacological and clinical studies on purine nucleoside analogs--new anticancer agents.	2006-05	16719832
Phase II study of clofarabine in pediatric patients with refractory or relapsed acute lymphoblastic leukemia.	2006-04-20	16622268
Treatment of older patients with acute myeloid leukemia--new agents.	2006-04	16616043
New drugs 06, part I.	2006-02	16462265
The structure of human deoxycytidine kinase in complex with clofarabine reveals key interactions for prodrug activation.	2006-02	16421443
Purine nucleoside analogs as immunosuppressive and antineoplastic agents: mechanism of action and clinical activity.	2006	17168705
New agents for the treatment of acute myeloid leukemia.	2006	16516128
Nucleosides as anticancer agents: from concept to the clinic.	2005	17150610
Effects of 2-chloro-9-(2-deoxy-2-fluoro-beta-D-arabinofuranosyl)adenine on K562 cellular metabolism and the inhibition of human ribonucleotide reductase and DNA polymerases by its 5'-triphosphate.	1991-05-01	1707752

Patents

Sample Use Guides

In Vivo Use Guide

The recommended pediatric dose is 52 mg/m2 given as an intravenous infusion over 2 hours daily for 5 consecutive days of a 28-day cycle. Repeat cycles every 2-6 week.

Route of Administration: Intravenous

In Vitro Use Guide

HL-60 cells or HL/ara-C20 cells were incubated with different concentrations of clofarabine for 72 h. The 50%-growth-inhibitory concentration IC50 was 50 nM for HL60 and 320 nM for HL/ara-C20 cells.

Substance Class	Chemical Created by `admin` on `Mon Mar 31 18:01:47 GMT 2025` Edited by `admin` on `Mon Mar 31 18:01:47 GMT 2025`
Record UNII	762RDY0Y2H
Record Status	`Validated (UNII)`
Record Version

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Name

Type

Language

CLOFARABINE

Official Name

English

CLOLAR

Preferred Name

English

CLOFARABINE [VANDF]

Common Name

English

CLOFARABINE [MI]

Common Name

English

9H-PURIN-6-AMINE, 2-CHLORO-9-(2-DEOXY-2-FLUORO-.BETA.-D-ARABINOFURANOSYL)

Common Name

English

clofarabine [INN]

Common Name

English

CLOFARABINE [ORANGE BOOK]

Common Name

English

Clofarabine [WHO-DD]

Common Name

English

NSC-759857

Code

English

CLOFARABINE [EMA EPAR]

Common Name

English

CLOFARABINE [USAN]

Common Name

English

CLOFARABINE [MART.]

Common Name

English

EVOLTRA

Brand Name

English

CLOFARABINE [JAN]

Common Name

English

2-CHLORO-9-(2-DEOXY-2-FLUORO-.BETA.-D-ARABINOFURANOSYL)-9H-PURIN-6-AMINE

Common Name

English

Classification Tree Code System Code

FDA ORPHAN DRUG

668118