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=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
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 |
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 |
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 |
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 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) 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 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) 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 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) 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 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) 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 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: |
PubMed
| Title | Date | PubMed |
|---|---|---|
| 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 |
|
| Clofarabine: in pediatric patients with acute lymphoblastic leukemia. | 2005 |
|
| Plasma and cerebrospinal fluid pharmacokinetics of clofarabine in nonhuman primates. | 2005 Aug 15 |
|
| Pediatric drug trials facing some obstacles. | 2005 Dec 7 |
|
| Gateways to clinical trials. | 2005 Jun |
|
| 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 |
|
| Purine nucleoside analogs as immunosuppressive and antineoplastic agents: mechanism of action and clinical activity. | 2006 |
|
| Efficacy of low dose clofarabine in refractory precursor T- acute lymphoblastic leukemia. | 2006 Dec |
|
| Nursing considerations for clofarabine in the treatment of acute lymphoblastic leukemia in children. | 2006 Dec |
|
| The structure of human deoxycytidine kinase in complex with clofarabine reveals key interactions for prodrug activation. | 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 |
|
| Clinical and pharmacokinetic study of clofarabine in chronic lymphocytic leukemia: strategy for treatment. | 2006 Jul 1 |
|
| Clofarabine and cytarabine combination as induction therapy for acute myeloid leukemia (AML) in patients 50 years of age or older. | 2006 Jul 1 |
|
| Pharmacological and clinical studies on purine nucleoside analogs--new anticancer agents. | 2006 May |
|
| Gateways to clinical trials. | 2006 Nov |
|
| The activity and toxicity of low dose clofarabine against relapsed or refractory myeloma. | 2006 Nov |
|
| Gateways to clinical trials. | 2006 Oct |
|
| New directions in the treatment of mantle cell lymphoma: an overview. | 2006 Oct |
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| A tale of two drugs. | 2006 Oct |
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| Discovery and development of clofarabine: a nucleoside analogue for treating cancer. | 2006 Oct |
|
| In vitro cytotoxicity of nelarabine, clofarabine and flavopiridol in paediatric acute lymphoblastic leukaemia. | 2007 Apr |
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| 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 |
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| Pharmacogenetics of deoxycytidine kinase: identification and characterization of novel genetic variants. | 2007 Dec |
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| Clofarabine for the treatment of acute lymphoblastic leukemia. | 2007 Feb |
|
| Saccharomyces cerevisiae emboli in an immunocompromised patient with relapsed acute myeloid leukaemia. | 2007 Jul |
|
| Cell cycle effect on the activity of deoxynucleoside analogue metabolising enzymes. | 2007 Jun 15 |
|
| Comparison of fast liquid chromatography/tandem mass spectrometric methods for simultaneous determination of cladribine and clofarabine in mouse plasma. | 2007 Jun 28 |
|
| Advances in the management of AML in the elderly. | 2007 Mar |
|
| Clofarabine: past, present, and future. | 2007 Oct |
|
| Clofarabine induced durable complete remission in heavily pretreated adolescents with relapsed and refractory leukemia. | 2007 Sep |
|
| A phase 1 clinical-laboratory study of clofarabine followed by cyclophosphamide for adults with refractory acute leukemias. | 2007 Sep 15 |
|
| 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 |
|
| 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 |
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| Acute myeloid leukemia in the elderly: conventional and novel treatment approaches. | 2008 Jul |
|
| Novel purine nucleoside analogues for hematological malignancies. | 2008 Jun |
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| Potential role of novel nucleoside analogs in the treatment of acute myeloid leukemia. | 2008 Mar |
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| Fatal skin and liver toxicity in a patient treated with clofarabine. | 2008 May |
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| Cytotoxic activities of nucleoside and nucleobase analog drugs in malignant mesothelioma: characterization of a novel nucleobase transport activity. | 2008 May 15 |
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| Clofarabine in refractory Langerhans cell histiocytosis. | 2008 Nov |
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| Polyadenylation inhibition by the triphosphates of deoxyadenosine analogues. | 2008 Oct |
|
| 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 |
|
| 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 Sep 1 |
|
| Enhancement of the in vivo antitumor activity of clofarabine by 1-beta-D-[4-thio-arabinofuranosyl]-cytosine. | 2009 Jul |
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
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9915350
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YPJ8ZV99ZP
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134646-41-6
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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
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PRODRUG (METABOLITE ACTIVE)
SUBSTANCE RECORD
