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
SMILES
NC1=NC(Cl)=NC2=C1N=CN2[C@@H]3O[C@H](COP(O)(=O)OP(O)(=O)OP(O)(O)=O)[C@@H](O)[C@@H]3F
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
DescriptionCurator's Comment: description was created based on several sources, including http://www.accessdata.fda.gov/drugsatfda_docs/label/2015/021673s024lbl.pdf
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.
Approval Year
Targets
| Primary Target | Pharmacology | Condition | Potency |
|---|---|---|---|
Target ID: CHEMBL2311221 |
|||
Target ID: CHEMBL2095215 |
17.0 nM [Ki] |
Conditions
| Condition | Modality | Targets | Highest Phase | Product |
|---|---|---|---|---|
| Primary | CLOLAR Approved UseClolar® (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 Date2004 |
Cmax
| 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 |
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 |
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: |
T1/2
| 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 |
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: |
unhealthy, 42 years Health Status: unhealthy Age Group: 42 years Sex: M+F Sources: |
Other AEs: Nausea, Diarrhea... Other AEs: Nausea (grade 1-2, 2 patients) Sources: Diarrhea (grade 1, 3 patients) Hepatotoxicity (grade 3, 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 Health Status: unhealthy Age Group: 42 years Sex: M+F Sources: |
Other AEs: Nausea, Fatigue... Other AEs: Nausea (grade 1-2, 3 patients) Sources: 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) |
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 Health Status: unhealthy Age Group: 51 years Sex: M+F 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 |
Other AEs: Nausea, Hypoalbuminemia... Other AEs: Nausea (grade 1-2, 1 patient) Sources: Hypoalbuminemia (grade 1-2, 1 patient) Blood bilirubin decreased (grade 1-2, 1 patient) Lymphopenia (grade 3-4) |
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 Health Status: unhealthy Age Group: child Sources: |
Other AEs: Hyperbilirubinemia, Vomiting... Other AEs: Hyperbilirubinemia (grade 4, 2 patients) Sources: Vomiting (grade 2-3, 2 patients) Maculopapular rash (grade 3, 2 patients) |
AEs
| AE | Significance | Dose | Population |
|---|---|---|---|
| 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 Health Status: unhealthy Age Group: 42 years Sex: M+F 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 Health Status: unhealthy Age Group: 42 years Sex: M+F 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 Health Status: unhealthy Age Group: 42 years Sex: M+F 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 Health Status: unhealthy Age Group: 42 years Sex: M+F 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 Health Status: unhealthy Age Group: 42 years Sex: M+F 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 Health Status: unhealthy Age Group: 42 years Sex: M+F 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 Health Status: unhealthy Age Group: 42 years Sex: M+F 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 Health Status: unhealthy Age Group: 42 years Sex: M+F 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 Health Status: unhealthy Age Group: 42 years Sex: M+F 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 Health Status: unhealthy Age Group: 42 years Sex: M+F 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 Health Status: unhealthy Age Group: 42 years Sex: M+F 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 Health Status: unhealthy Age Group: 51 years Sex: M+F 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 |
| 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 |
| 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 |
| 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 |
| 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 Health Status: unhealthy Age Group: child 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 Health Status: unhealthy Age Group: child 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 Health Status: unhealthy Age Group: child Sources: |
PubMed
| Title | Date | PubMed |
|---|---|---|
| Enhancement of the in vivo antitumor activity of clofarabine by 1-beta-D-[4-thio-arabinofuranosyl]-cytosine. | 2009-07 |
|
| Clofarabine in refractory Langerhans cell histiocytosis. | 2008-11 |
|
| Clofarabine: in search of combinations for the treatment of patients with high-risk acute myeloid leukemia. | 2008-10-15 |
|
| Clofarabine combinations as acute myeloid leukemia salvage therapy. | 2008-10-15 |
|
| Polyadenylation inhibition by the triphosphates of deoxyadenosine analogues. | 2008-10 |
|
| 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 |
|
| Contribution of the drug transporter ABCG2 (breast cancer resistance protein) to resistance against anticancer nucleosides. | 2008-09 |
|
| Synthetic studies on formamidopyrimidines related to clofarabine. | 2008-08 |
|
| New drugs in acute myeloid leukemia. | 2008-08 |
|
| Acute myeloid leukemia in the elderly. | 2008-08 |
|
| Acute myeloid leukemia in the elderly: conventional and novel treatment approaches. | 2008-07 |
|
| Novel purine nucleoside analogues for hematological malignancies. | 2008-06 |
|
| Cytotoxic activities of nucleoside and nucleobase analog drugs in malignant mesothelioma: characterization of a novel nucleobase transport activity. | 2008-05-15 |
|
| Fatal skin and liver toxicity in a patient treated with clofarabine. | 2008-05 |
|
| Treating refractory leukemias in childhood, role of clofarabine. | 2008-04 |
|
| Potential role of novel nucleoside analogs in the treatment of acute myeloid leukemia. | 2008-03 |
|
| Clofarabine acts as radiosensitizer in vitro and in vivo by interfering with DNA damage response. | 2008-01-01 |
|
| Cytotoxic nucleoside analogues: different strategies to improve their clinical efficacy. | 2008 |
|
| The combination of clofarabine and cytarabine in pediatric relapsed acute lymphoblastic leukemia: a case report. | 2008 |
|
| Clofarabine: new drug. Children with acute lymphoblastic leukaemia: a last resort. | 2007-12 |
|
| Three new drugs for acute lymphoblastic leukemia: nelarabine, clofarabine, and forodesine. | 2007-12 |
|
| Pharmacogenetics of deoxycytidine kinase: identification and characterization of novel genetic variants. | 2007-12 |
|
| Clofarabine: past, present, and future. | 2007-10 |
|
| A phase 1 clinical-laboratory study of clofarabine followed by cyclophosphamide for adults with refractory acute leukemias. | 2007-09-15 |
|
| Clofarabine induced durable complete remission in heavily pretreated adolescents with relapsed and refractory leukemia. | 2007-09 |
|
| Saccharomyces cerevisiae emboli in an immunocompromised patient with relapsed acute myeloid leukaemia. | 2007-07 |
|
| Comparison of fast liquid chromatography/tandem mass spectrometric methods for simultaneous determination of cladribine and clofarabine in mouse plasma. | 2007-06-28 |
|
| Cell cycle effect on the activity of deoxynucleoside analogue metabolising enzymes. | 2007-06-15 |
|
| In vitro cytotoxicity of nelarabine, clofarabine and flavopiridol in paediatric acute lymphoblastic leukaemia. | 2007-04 |
|
| Advances in the management of AML in the elderly. | 2007-03 |
|
| Clofarabine for the treatment of acute lymphoblastic leukemia. | 2007-02 |
|
| Efficacy of low dose clofarabine in refractory precursor T- acute lymphoblastic leukemia. | 2006-12 |
|
| Nursing considerations for clofarabine in the treatment of acute lymphoblastic leukemia in children. | 2006-12 |
|
| Gateways to clinical trials. | 2006-11 |
|
| The activity and toxicity of low dose clofarabine against relapsed or refractory myeloma. | 2006-11 |
|
| Clofarabine and nelarabine: two new purine nucleoside analogs. | 2006-11 |
|
| Gateways to clinical trials. | 2006-10 |
|
| New directions in the treatment of mantle cell lymphoma: an overview. | 2006-10 |
|
| A tale of two drugs. | 2006-10 |
|
| Discovery and development of clofarabine: a nucleoside analogue for treating cancer. | 2006-10 |
|
| Clinical and pharmacokinetic study of clofarabine in chronic lymphocytic leukemia: strategy for treatment. | 2006-07-01 |
|
| Pharmacological and clinical studies on purine nucleoside analogs--new anticancer agents. | 2006-05 |
|
| Phase II study of clofarabine in pediatric patients with refractory or relapsed acute lymphoblastic leukemia. | 2006-04-20 |
|
| Treatment of older patients with acute myeloid leukemia--new agents. | 2006-04 |
|
| New drugs 06, part I. | 2006-02 |
|
| The structure of human deoxycytidine kinase in complex with clofarabine reveals key interactions for prodrug activation. | 2006-02 |
|
| Purine nucleoside analogs as immunosuppressive and antineoplastic agents: mechanism of action and clinical activity. | 2006 |
|
| New agents for the treatment of acute myeloid leukemia. | 2006 |
|
| Nucleosides as anticancer agents: from concept to the clinic. | 2005 |
|
| 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 |
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
| Name | Type | Language | ||
|---|---|---|---|---|
|
Common Name | English | ||
|
Preferred Name | English | ||
|
Systematic Name | English |
| Code System | Code | Type | Description | ||
|---|---|---|---|---|---|
|
9915350
Created by
admin on Wed Apr 02 15:39:01 GMT 2025 , Edited by admin on Wed Apr 02 15:39:01 GMT 2025
|
PRIMARY | |||
|
YPJ8ZV99ZP
Created by
admin on Wed Apr 02 15:39:01 GMT 2025 , Edited by admin on Wed Apr 02 15:39:01 GMT 2025
|
PRIMARY | |||
|
134646-41-6
Created by
admin on Wed Apr 02 15:39:01 GMT 2025 , Edited by admin on Wed Apr 02 15:39:01 GMT 2025
|
PRIMARY | |||
|
DTXSID00432746
Created by
admin on Wed Apr 02 15:39:01 GMT 2025 , Edited by admin on Wed Apr 02 15:39:01 GMT 2025
|
PRIMARY |
PRODRUG (METABOLITE ACTIVE)
SUBSTANCE RECORD
