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Details

Stereochemistry ABSOLUTE
Molecular Formula C10H14ClFN5O12P3
Molecular Weight 543.617
Optical Activity UNSPECIFIED
Defined Stereocenters 4 / 4
E/Z Centers 0
Charge 0

SHOW SMILES / InChI
Structure of Clofarabine triphosphate

SMILES

NC1=C2N=CN([C@@H]3O[C@H](COP(O)(=O)OP(O)(=O)OP(O)(O)=O)[C@@H](O)[C@@H]3F)C2=NC(Cl)=N1

InChI

InChIKey=ILZCVFJUTWHERD-AYQXTPAHSA-N
InChI=1S/C10H14ClFN5O12P3/c11-10-15-7(13)5-8(16-10)17(2-14-5)9-4(12)6(18)3(27-9)1-26-31(22,23)29-32(24,25)28-30(19,20)21/h2-4,6,9,18H,1H2,(H,22,23)(H,24,25)(H2,13,15,16)(H2,19,20,21)/t3-,4+,6-,9-/m1/s1

HIDE SMILES / InChI

Molecular Formula C10H14ClFN5O12P3
Molecular Weight 543.617
Charge 0
Count
Stereochemistry ABSOLUTE
Additional Stereochemistry No
Defined Stereocenters 4 / 4
E/Z Centers 0
Optical Activity UNSPECIFIED

Description
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

Curator's Comment: Only a small amount of the drug was shown to cross the blood brain barrier in non-human primates.

Approval Year

TargetsConditions

Conditions

ConditionModalityTargetsHighest PhaseProduct
Primary
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
Cmax

Cmax

ValueDoseCo-administeredAnalytePopulation
308 ng/mL
40 mg/m² 1 times / day multiple, intravenous
dose: 40 mg/m²
route of administration: Intravenous
experiment type: MULTIPLE
co-administered: CYTARABINE
CLOFARABINE plasma
Homo sapiens
population: UNHEALTHY
age: ADULT
sex: FEMALE / MALE
food status: UNKNOWN
AUC

AUC

ValueDoseCo-administeredAnalytePopulation
1793 ng × h/mL
40 mg/m² 1 times / day multiple, intravenous
dose: 40 mg/m²
route of administration: Intravenous
experiment type: MULTIPLE
co-administered: CYTARABINE
CLOFARABINE plasma
Homo sapiens
population: UNHEALTHY
age: ADULT
sex: FEMALE / MALE
food status: UNKNOWN
28 ng × h/mL
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
T1/2

T1/2

ValueDoseCo-administeredAnalytePopulation
4.9 h
40 mg/m² 1 times / day multiple, intravenous
dose: 40 mg/m²
route of administration: Intravenous
experiment type: MULTIPLE
co-administered: CYTARABINE
CLOFARABINE plasma
Homo sapiens
population: UNHEALTHY
age: ADULT
sex: FEMALE / MALE
food status: UNKNOWN
1.5 h
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
Doses

Doses

DosePopulationAdverse 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:
unhealthy, 42 years
n = 4
Health Status: unhealthy
Condition: acute leukemia
Age Group: 42 years
Sex: M+F
Population Size: 4
Sources:
Other AEs: Nausea, Diarrhea...
Other AEs:
Nausea (grade 1-2, 2 patients)
Diarrhea (grade 1, 3 patients)
Hepatotoxicity (grade 3, 2 patients)
Sources:
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:
unhealthy, 42 years
n = 31
Health Status: unhealthy
Condition: acute leukemia
Age Group: 42 years
Sex: M+F
Population Size: 31
Sources:
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:
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:
unhealthy, 51 years
n = 6
Health Status: unhealthy
Condition: solid tumors
Age Group: 51 years
Sex: M+F
Population Size: 6
Sources:
DLT: Myelosuppression...
Dose limiting toxicities:
Myelosuppression (grade 3, 2 patients)
Sources:
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:
unhealthy, 60-76 years
n = 1
Health Status: unhealthy
Condition: Acute Myeloid Leukemia
Age Group: 60-76 years
Population Size: 1
Sources:
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:
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:
unhealthy, child
n = 2
Health Status: unhealthy
Condition: ALL
Age Group: child
Population Size: 2
Sources:
Other AEs: Hyperbilirubinemia, Vomiting...
Other AEs:
Hyperbilirubinemia (grade 4, 2 patients)
Vomiting (grade 2-3, 2 patients)
Maculopapular rash (grade 3, 2 patients)
Sources:
AEs

AEs

AESignificanceDosePopulation
Diarrhea grade 1, 3 patients
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:
unhealthy, 42 years
n = 4
Health Status: unhealthy
Condition: acute leukemia
Age Group: 42 years
Sex: M+F
Population Size: 4
Sources:
Nausea grade 1-2, 2 patients
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:
unhealthy, 42 years
n = 4
Health Status: unhealthy
Condition: acute leukemia
Age Group: 42 years
Sex: M+F
Population Size: 4
Sources:
Hepatotoxicity grade 3, 2 patients
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:
unhealthy, 42 years
n = 4
Health Status: unhealthy
Condition: acute leukemia
Age Group: 42 years
Sex: M+F
Population Size: 4
Sources:
Anorexia grade 1, 1 patient
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:
unhealthy, 42 years
n = 31
Health Status: unhealthy
Condition: acute leukemia
Age Group: 42 years
Sex: M+F
Population Size: 31
Sources:
Cramp grade 1, 1 patient
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:
unhealthy, 42 years
n = 31
Health Status: unhealthy
Condition: acute leukemia
Age Group: 42 years
Sex: M+F
Population Size: 31
Sources:
Edema grade 1, 1 patient
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:
unhealthy, 42 years
n = 31
Health Status: unhealthy
Condition: acute leukemia
Age Group: 42 years
Sex: M+F
Population Size: 31
Sources:
Mucositis grade 1, 1 patient
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:
unhealthy, 42 years
n = 31
Health Status: unhealthy
Condition: acute leukemia
Age Group: 42 years
Sex: M+F
Population Size: 31
Sources:
Diarrhea grade 1, 2 patients
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:
unhealthy, 42 years
n = 31
Health Status: unhealthy
Condition: acute leukemia
Age Group: 42 years
Sex: M+F
Population Size: 31
Sources:
Nausea grade 1-2, 3 patients
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:
unhealthy, 42 years
n = 31
Health Status: unhealthy
Condition: acute leukemia
Age Group: 42 years
Sex: M+F
Population Size: 31
Sources:
Fatigue grade 3, 1 patient
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:
unhealthy, 42 years
n = 31
Health Status: unhealthy
Condition: acute leukemia
Age Group: 42 years
Sex: M+F
Population Size: 31
Sources:
Hepatotoxicity grade 3-4, 4 patients
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:
unhealthy, 42 years
n = 31
Health Status: unhealthy
Condition: acute leukemia
Age Group: 42 years
Sex: M+F
Population Size: 31
Sources:
Myelosuppression grade 3, 2 patients
DLT
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:
unhealthy, 51 years
n = 6
Health Status: unhealthy
Condition: solid tumors
Age Group: 51 years
Sex: M+F
Population Size: 6
Sources:
Blood bilirubin decreased grade 1-2, 1 patient
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:
unhealthy, 60-76 years
n = 1
Health Status: unhealthy
Condition: Acute Myeloid Leukemia
Age Group: 60-76 years
Population Size: 1
Sources:
Hypoalbuminemia grade 1-2, 1 patient
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:
unhealthy, 60-76 years
n = 1
Health Status: unhealthy
Condition: Acute Myeloid Leukemia
Age Group: 60-76 years
Population Size: 1
Sources:
Nausea grade 1-2, 1 patient
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:
unhealthy, 60-76 years
n = 1
Health Status: unhealthy
Condition: Acute Myeloid Leukemia
Age Group: 60-76 years
Population Size: 1
Sources:
Lymphopenia grade 3-4
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:
unhealthy, 60-76 years
n = 1
Health Status: unhealthy
Condition: Acute Myeloid Leukemia
Age Group: 60-76 years
Population Size: 1
Sources:
Vomiting grade 2-3, 2 patients
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:
unhealthy, child
n = 2
Health Status: unhealthy
Condition: ALL
Age Group: child
Population Size: 2
Sources:
Maculopapular rash grade 3, 2 patients
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:
unhealthy, child
n = 2
Health Status: unhealthy
Condition: ALL
Age Group: child
Population Size: 2
Sources:
Hyperbilirubinemia grade 4, 2 patients
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:
unhealthy, child
n = 2
Health Status: unhealthy
Condition: ALL
Age Group: child
Population Size: 2
Sources:
Overview

Overview

CYP3A4CYP2C9CYP2D6hERG

OverviewOther

Other InhibitorOther SubstrateOther Inducer

Drug as victim

Drug as victim

TargetModalityActivityMetaboliteClinical evidence
no
Tox targets

Tox targets

TargetModalityActivityMetaboliteClinical evidence
PubMed

PubMed

TitleDatePubMed
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 May 1
Mechanisms of the apoptotic activity of Cl-F-araA in a human T-ALL cell line, CCRF-CEM.
2002 Sep
Pharmacokinetics and pharmacodynamics of plasma clofarabine and cellular clofarabine triphosphate in patients with acute leukemias.
2003 Dec 15
Advanced-phase chronic myeloid leukemia.
2003 Jan
Down-regulation of deoxycytidine kinase in human leukemic cell lines resistant to cladribine and clofarabine and increased ribonucleotide reductase activity contributes to fludarabine resistance.
2003 Jan 15
New designs for phase 2 clinical trials.
2003 Jul 15
Gateways to clinical trials.
2003 Nov
Phase 2 clinical and pharmacologic study of clofarabine in patients with refractory or relapsed acute leukemia.
2003 Oct 1
Prognostic factors and therapeutic options for relapsed or refractory acute myeloid leukemia.
2004 Aug
Gateways to clinical trials.
2004 Jul-Aug
Purine nucleoside antimetabolites in development for the treatment of cancer.
2004 Jun
New nucleoside analogs in the treatment of hematological disorders.
2004 May-Jun
Population pharmacokinetics of clofarabine, a second-generation nucleoside analog, in pediatric patients with acute leukemia.
2004 Nov
Clofarabine: in pediatric patients with acute lymphoblastic leukemia.
2005
Plasma and cerebrospinal fluid pharmacokinetics of clofarabine in nonhuman primates.
2005 Aug 15
New drugs and dosage forms.
2005 Feb 1
Results of a phase 1-2 study of clofarabine in combination with cytarabine (ara-C) in relapsed and refractory acute leukemias.
2005 Feb 1
New agents in the treatment of childhood leukemias and myelodysplastic syndromes.
2005 Nov
Gateways to clinical trials.
2005 Sep
Purine nucleoside analogues for the treatment of hematological malignancies: pharmacology and clinical applications.
2005 Sep
New drugs: tigecycline, ziconotide, and clofarabine.
2005 Sep-Oct
Efficacy of low dose clofarabine in refractory precursor T- acute lymphoblastic leukemia.
2006 Dec
New drugs 06, part I.
2006 Feb
A comparison of the transportability, and its role in cytotoxicity, of clofarabine, cladribine, and fludarabine by recombinant human nucleoside transporters produced in three model expression systems.
2006 Jan
The activity and toxicity of low dose clofarabine against relapsed or refractory myeloma.
2006 Nov
Clofarabine and nelarabine: two new purine nucleoside analogs.
2006 Nov
Gateways to clinical trials.
2006 Oct
New directions in the treatment of mantle cell lymphoma: an overview.
2006 Oct
Discovery and development of clofarabine: a nucleoside analogue for treating cancer.
2006 Oct
Clofarabine: new drug. Children with acute lymphoblastic leukaemia: a last resort.
2007 Dec
Three new drugs for acute lymphoblastic leukemia: nelarabine, clofarabine, and forodesine.
2007 Dec
Pharmacogenetics of deoxycytidine kinase: identification and characterization of novel genetic variants.
2007 Dec
Clofarabine for the treatment of acute lymphoblastic leukemia.
2007 Feb
Clofarabine: past, present, and future.
2007 Oct
Clofarabine induced durable complete remission in heavily pretreated adolescents with relapsed and refractory leukemia.
2007 Sep
Treating refractory leukemias in childhood, role of clofarabine.
2008 Apr
Clofarabine acts as radiosensitizer in vitro and in vivo by interfering with DNA damage response.
2008 Jan 1
Fatal skin and liver toxicity in a patient treated with clofarabine.
2008 May
Cytotoxic activities of nucleoside and nucleobase analog drugs in malignant mesothelioma: characterization of a novel nucleobase transport activity.
2008 May 15
Clofarabine in refractory Langerhans cell histiocytosis.
2008 Nov
Clofarabine: in search of combinations for the treatment of patients with high-risk acute myeloid leukemia.
2008 Oct 15
Clofarabine combinations as acute myeloid leukemia salvage therapy.
2008 Oct 15
Contribution of the drug transporter ABCG2 (breast cancer resistance protein) to resistance against anticancer nucleosides.
2008 Sep
Enhancement of the in vivo antitumor activity of clofarabine by 1-beta-D-[4-thio-arabinofuranosyl]-cytosine.
2009 Jul
Patents

Patents

Sample Use Guides

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
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 Sat Dec 16 19:23:27 GMT 2023
Edited
by admin
on Sat Dec 16 19:23:27 GMT 2023
Record UNII
YPJ8ZV99ZP
Record Status Validated (UNII)
Record Version
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Name Type Language
Clofarabine triphosphate
Common Name English
9H-Purin-6-amine, 2-chloro-9-[2-deoxy-2-fluoro-5-O-[hydroxy[[hydroxy(phosphonooxy)phosphinyl]oxy]phosphinyl]-β-D-arabinofuranosyl]-
Systematic Name English
2-Chloro-9-[2-deoxy-2-fluoro-5-O-[hydroxy[[hydroxy(phosphonooxy)phosphinyl]oxy]phosphinyl]-β-D-arabinofuranosyl]-9H-purin-6-amine
Systematic Name English
Code System Code Type Description
PUBCHEM
9915350
Created by admin on Sat Dec 16 19:23:27 GMT 2023 , Edited by admin on Sat Dec 16 19:23:27 GMT 2023
PRIMARY
FDA UNII
YPJ8ZV99ZP
Created by admin on Sat Dec 16 19:23:27 GMT 2023 , Edited by admin on Sat Dec 16 19:23:27 GMT 2023
PRIMARY
CAS
134646-41-6
Created by admin on Sat Dec 16 19:23:27 GMT 2023 , Edited by admin on Sat Dec 16 19:23:27 GMT 2023
PRIMARY
EPA CompTox
DTXSID00432746
Created by admin on Sat Dec 16 19:23:27 GMT 2023 , Edited by admin on Sat Dec 16 19:23:27 GMT 2023
PRIMARY
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