Identification

Name
Clofarabine
Accession Number
DB00631  (APRD00878, DB07554, DB06189)
Type
Small Molecule
Groups
Approved, Investigational
Description

Clofarabine is a purine nucleoside antimetabolite that is being studied in the treatment of cancer. It is marketed in the U.S. and Canada as Clolar. In Europe and Australia/New Zealand the product is marketed under the name Evoltra.

Clofarabine is used in paediatrics to treat a type of leukaemia called relapsed or refractory acute lymphoblastic leukaemia (ALL), only after at least two other types of treatment have failed. It is not known if the drug extends life expectancy. Some investigations of effectiveness in cases of acute myeloid leukaemia (AML) and juvenile myelomonocytic leukaemia (JMML) have been carried out.

Structure
Thumb
Synonyms
  • (2R,3R,4S,5R)-5-(6-amino-2-Chloropurin-9-yl)-4-fluoro-2-(hydroxymethyl)oxolan-3-ol
  • 2-chloro-9-(2-Deoxy-2-fluoro-beta-D-arabinofuranosyl)adenine
  • 2-chloro-9-(2'-Deoxy-2'-fluoro-beta-D-arabinofuranosyl)adenine
  • CAFdA
  • CL-F-Ara-a
  • Clofarabin
  • Clofarabina
  • Clofarabine
  • Clofarabinum
  • Clofarex
External IDs
C1-F-Ara-A / CAfdA
Prescription Products
NameDosageStrengthRouteLabellerMarketing StartMarketing End
ClolarSolution1 mgIntravenousSanofi Aventis2010-02-10Not applicableCanada
ClolarInjection1 mg/1mLIntravenousSanofi Aventis2013-04-01Not applicableUs
ClolarInjection1 mg/1mLIntravenousSanofi Aventis2017-07-01Not applicableUs
ClolarInjection1 mg/1mLIntravenousGenzyme Corporation2004-12-282013-03-31Us
EvoltraInjection, solution, concentrate1 mg/mlIntravenousGenzyme Europe Bv2006-05-29Not applicableEu
EvoltraInjection, solution, concentrate1 mg/mlIntravenousGenzyme Europe Bv2006-05-29Not applicableEu
EvoltraInjection, solution, concentrate1 mg/mlIntravenousGenzyme Europe Bv2006-05-29Not applicableEu
EvoltraInjection, solution, concentrate1 mg/mlIntravenousGenzyme Europe Bv2006-05-29Not applicableEu
EvoltraInjection, solution, concentrate1 mg/mlIntravenousGenzyme Europe Bv2006-05-29Not applicableEu
Generic Prescription Products
NameDosageStrengthRouteLabellerMarketing StartMarketing End
ClofarabineInjection1 mg/1mLIntravenousAmneal Biosciences Llc2017-11-06Not applicableUs
ClofarabineInjection1 mg/1mLIntravenousDr Reddy's Laboratories2017-11-08Not applicableUs
ClofarabineInjection1 mg/1mLIntravenousApotex Corporation2018-01-01Not applicableUs
ClofarabineInjection1 mg/1mLIntravenousMylan Institutional2017-11-06Not applicableUs
ClofarabineInjection1 mg/1mLIntravenousFresenius-Kabi2017-05-10Not applicableUs
ClofarabineInjection1 mg/1mLIntravenousSanofi Aventis2017-05-11Not applicableUs
International/Other Brands
Clofazic (Raffo) / Clolar / Evoltra (Genzyme)
Categories
UNII
762RDY0Y2H
CAS number
123318-82-1
Weight
Average: 303.677
Monoisotopic: 303.053445155
Chemical Formula
C10H11ClFN5O3
InChI Key
WDDPHFBMKLOVOX-AYQXTPAHSA-N
InChI
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
IUPAC Name
(2R,3R,4S,5R)-5-(6-amino-2-chloro-9H-purin-9-yl)-4-fluoro-2-(hydroxymethyl)oxolan-3-ol
SMILES
[H][C@]1(F)[C@H](O)[C@@H](CO)O[C@H]1N1C=NC2=C(N)N=C(Cl)N=C12

Pharmacology

Indication

For the treatment of pediatric patients 1 to 21 years old with relapsed or refractory acute lymphocytic (lymphoblastic) leukemia after at least two prior regimens. It is designated as an orphan drug by the FDA for this use.

Associated Conditions
Pharmacodynamics

Clofarabine is a purine nucleoside antimetabolite that differs from other puring nucleoside analogs by the presence of a chlorine in the purine ring and a flourine in the ribose moiety. Clofarabine seems to interfere with the growth of cancer cells, which are eventually destroyed. Since the growth of normal body cells may also be affected by clofarabine, other effects also occur. Clofarabine prevents cells from making DNA and RNA by interfering with the synthesis of nucleic acids, thus stopping the growth of cancer cells.

Mechanism of action

Clofarabine is metabolized intracellularly to the active 5'-monophosphate metabolite by deoxycytidine kinase and 5'-triphosphate metabolite by mono- and di-phospho-kinases. This metabolite inhibits DNA synthesis through an inhibitory action on ribonucleotide reductase, and by terminating DNA chain elongation and inhibiting repair through competitive inhibition of DNA polymerases. This leads to the depletion of the intracellular deoxynucleotide triphosphate pool and the self-potentiation of clofarabine triphosphate incorporation into DNA, thereby intensifying the effectiveness of DNA synthesis inhibition. The affinity of clofarabine triphosphate for these enzymes is similar to or greater than that of deoxyadenosine triphosphate. In preclinical models, clofarabine has demonstrated the ability to inhibit DNA repair by incorporation into the DNA chain during the repair process. Clofarabine 5'-triphosphate also disrupts the integrity of mitochondrial membrane, leading to the release of the pro-apoptotic mitochondrial proteins, cytochrome C and apoptosis-inducing factor, leading to programmed cell death.

TargetActionsOrganism
ADNA polymerase alpha catalytic subunit
inhibitor
Human
ARibonucleoside-diphosphate reductase large subunit
inhibitor
Human
ADNA
other/unknown
Human
Absorption
Not Available
Volume of distribution
  • 172 L/m2
Protein binding

47% bound to plasma proteins, predominantly to albumin.

Metabolism

Clofarabine is sequentially metabolized intracellularly to the 5’-monophosphate metabolite by deoxycytidine kinase and mono- and di-phosphokinases to the active 5’-triphosphate metabolite. Clofarabine has high affinity for the activating phosphorylating enzyme, deoxycytidine kinase, equal to or greater than that of the natural substrate, deoxycytidine.

Route of elimination

Based on 24-hour urine collections in the pediatric studies, 49 - 60% of the dose is excreted in the urine unchanged.

Half life

The terminal half-life is estimated to be 5.2 hours.

Clearance
  • 28.8 L/h/m2 [Pediatric patients (2 - 19 years old) with relapsed or refractory acute lymphoblastic leukemia (ALL) or acute myelogenous leukemia (AML) receiving 52 mg/m2 dose]
Toxicity

There were no known overdoses of clofarabine. The highest daily dose administered to a human to date (on a mg/m2 basis) has been 70 mg/m2/day × 5 days (2 pediatric ALL patients). The toxicities included in these 2 patients included grade 4 hyperbilirubinemia, grade 2 and 3 vomiting, and grade 3 maculopapular rash.

Affected organisms
  • Humans and other mammals
Pathways
Not Available
Pharmacogenomic Effects/ADRs
Not Available

Interactions

Drug Interactions
DrugInteraction
AcebutololThe risk or severity of adverse effects can be increased when Clofarabine is combined with Acebutolol.
AcetaminophenAcetaminophen may decrease the excretion rate of Clofarabine which could result in a higher serum level.
AcetyldigitoxinAcetyldigitoxin may decrease the cardiotoxic activities of Clofarabine.
AcetyldigoxinAcetyldigoxin may decrease the cardiotoxic activities of Clofarabine.
Acetylsalicylic acidAcetylsalicylic acid may decrease the excretion rate of Clofarabine which could result in a higher serum level.
AdalimumabThe risk or severity of adverse effects can be increased when Adalimumab is combined with Clofarabine.
AlclometasoneThe risk or severity of adverse effects can be increased when Clofarabine is combined with Alclometasone.
AldesleukinThe risk or severity of adverse effects can be increased when Clofarabine is combined with Aldesleukin.
AlemtuzumabThe risk or severity of adverse effects can be increased when Alemtuzumab is combined with Clofarabine.
AliskirenThe risk or severity of adverse effects can be increased when Clofarabine is combined with Aliskiren.
Food Interactions
  • Echinacea should be used with caution, if at all, in patients receiving therapeutic immunosuppressants. Monitor for reduced efficacy of the immunosuppressant during concomitant use.

References

General References
  1. Pession A, Masetti R, Kleinschmidt K, Martoni A: Use of clofarabine for acute childhood leukemia. Biologics. 2010 Jun 24;4:111-8. [PubMed:20631817]
  2. Harned TM, Gaynon PS: Treating refractory leukemias in childhood, role of clofarabine. Ther Clin Risk Manag. 2008 Apr;4(2):327-36. [PubMed:18728851]
  3. Lech-Maranda E, Korycka A, Robak T: Clofarabine as a novel nucleoside analogue approved to treat patients with haematological malignancies: mechanism of action and clinical activity. Mini Rev Med Chem. 2009 Jun;9(7):805-12. [PubMed:19519505]
  4. Larson ML, Venugopal P: Clofarabine: a new treatment option for patients with acute myeloid leukemia. Expert Opin Pharmacother. 2009 Jun;10(8):1353-7. doi: 10.1517/14656560902997990. [PubMed:19463072]
  5. Zhenchuk A, Lotfi K, Juliusson G, Albertioni F: Mechanisms of anti-cancer action and pharmacology of clofarabine. Biochem Pharmacol. 2009 Dec 1;78(11):1351-9. doi: 10.1016/j.bcp.2009.06.094. Epub 2009 Jul 1. [PubMed:19576186]
External Links
Human Metabolome Database
HMDB0014769
PubChem Compound
119182
PubChem Substance
46504968
ChemSpider
106472
ChEBI
681569
ChEMBL
CHEMBL1750
Therapeutic Targets Database
DAP000849
PharmGKB
PA164754863
HET
CFB
RxList
RxList Drug Page
Drugs.com
Drugs.com Drug Page
Wikipedia
Clofarabine
ATC Codes
L01BB06 — Clofarabine
AHFS Codes
  • 10:00.00 — Antineoplastic Agents
PDB Entries
2a7q
FDA label
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Clinical Trials

Clinical Trials
PhaseStatusPurposeConditionsCount
1Active Not RecruitingTreatmentAcute Lymphocytic Leukemia (ALL) / Hodgkins Disease (HD) / Leukemia Acute Myeloid Leukemia (AML) / Myelodysplastic Syndrome / Relapsed or Refractory Chronic Lymphocytic Leukemia (CLL) / Relapsed Refractory Multiple Myeloma / Relapsed/Refractory Non Hodgkin's Lymphoma1
1Active Not RecruitingTreatmentLeukemias1
1CompletedNot AvailableLeukemia, Lymphocytic, Acute, Adult / Leukemia, Lymphocytic, Acute, Pediatric / Leukemia, Myelocytic, Acute, Adult / Leukemia, Myelocytic, Acute, Pediatric / Myelodysplastic Syndromes, Adult / Tumors, Solid1
1CompletedTreatmentAcute Leukemias of Ambiguous Lineage / Philadelphia Chromosome Negative Adult Precursor Acute Lymphoblastic Leukemia / Recurrent Adult Acute Lymphoblastic Leukemia / Untreated Adult Acute Lymphoblastic Leukemia1
1CompletedTreatmentAcute Lymphoblastic Leukaemias (ALL)1
1CompletedTreatmentAcute Lymphoblastic Leukaemias (ALL) / Chronic Chronic myelogenous leukemia / Juvenile Myelomonocytic Leukemia / Myelodysplastic Syndrome / Non-Hodgkin's Lymphoma (NHL)1
1CompletedTreatmentAcute Lymphoid Leukemia Relapse / Acute Lymphoid Leukemia Relapse After Bone Marrow Transplant1
1CompletedTreatmentAcute Myelogenous Leukaemia (AML)1
1CompletedTreatmentAdult Acute Megakaryoblastic Leukemia (M7) / Adult Acute Minimally Differentiated Myeloid Leukemia (M0) / Adult Acute Monoblastic Leukemia (M5a) / Adult Acute Monocytic Leukemia (M5b) / Adult Acute Myeloblastic Leukemia With Maturation (M2) / Adult Acute Myeloblastic Leukemia Without Maturation (M1) / Adult Acute Myeloid Leukemia With 11q23 (MLL) Abnormalities / Adult Acute Myeloid Leukemia With Del(5q) / Adult Acute Myeloid Leukemia With Inv(16)(p13;q22) / Adult Acute Myeloid Leukemia With T(15;17)(q22;q12) / Adult Acute Myeloid Leukemia With T(16;16)(p13;q22) / Adult Acute Myeloid Leukemia With T(8;21)(q22;q22) / Adult Acute Myelomonocytic Leukemia (M4) / Adult Acute Promyelocytic Leukemia (M3) / Adult Erythroleukemia (M6a) / Adult Pure Erythroid Leukemia (M6b) / Recurrent Adult Acute Myeloid Leukemia / Untreated Adult Acute Myeloid Leukemia1
1CompletedTreatmentBiphenotypic Leukemia / Infantile Leukemia (Both AML and ALL) / Leukemia Acute Myeloid Leukemia (AML) / Myelodysplastic Syndrome / Myelodysplastic/Myeloproliferative Neoplasms1
1CompletedTreatmentBlood And Marrow Transplantation / Leukemias / Malignant Lymphomas / Transplantation Infection / Transplantation, Bone Marrow1
1CompletedTreatmentBone Marrow Diseases / Chronic Myelomonocytic Leukemia / Leukemia Acute Myeloid Leukemia (AML) / Myeldysplastic Syndrome (MDS) / Neutropenias1
1CompletedTreatmentChronic Lymphocytic Leukaemia (CLL) / Leukemias / Lymphoproliferative Disorders / Neoplasms, Hematologic1
1CompletedTreatmentChronic Myeloproliferative Disorders / Leukemias / Myelodysplastic/Myeloproliferative Diseases1
1CompletedTreatmentLeukemia Acute Myeloid Leukemia (AML)2
1CompletedTreatmentLeukemia Acute Myeloid Leukemia (AML) / Leukemia Lymphoblastic, Acute / Recurrent Neoplasm1
1CompletedTreatmentLeukemia, Acute / Lymphoma, Hodgkins / Non-Hodgkin's Lymphoma (NHL)1
1CompletedTreatmentLeukemias3
1CompletedTreatmentLeukemias / Myelodysplastic Syndrome1
1CompletedTreatmentLeukemias / Myelodysplastic Syndromes1
1CompletedTreatmentLymphoblastic Leukemia, Acute, Childhood1
1CompletedTreatmentLymphoma, B-Cell1
1CompletedTreatmentMalignancies, Hematologic2
1CompletedTreatmentNon Hodgkin Lymphoma (NHL)1
1CompletedTreatmentTumors, Solid1
1TerminatedBasic ScienceAcute Lymphoblastic Leukaemias (ALL) / Chronic Myelomonocytic Leukemia / Leukemia Acute Myeloid Leukemia (AML) / Myelodysplastic Syndrome1
1TerminatedTreatmentAcute Lymphocytic Leukemia (ALL) / Acute Promyelocytic Leukemia (APL) / Agnogenic Myeloid Metaplasia / Chronic Chronic myelogenous leukemia / Chronic Myelomonocytic Leukemia / Juvenile Myelomonocytic Leukemia / Leukemia Acute Myeloid Leukemia (AML) / Leukemia, Acute / Myelodysplastic Syndrome / Myeloproliferative Disorders1
1TerminatedTreatmentChronic Lymphocytic Leukaemia (CLL) / Leukemias1
1TerminatedTreatmentLeukemias1
1TerminatedTreatmentMyelodysplastic Syndrome1
1TerminatedTreatmentMyelodysplastic Syndromes1
1WithdrawnTreatmentChronic Lymphocytic Leukaemia (CLL) / Leukemias1
1WithdrawnTreatmentLeukemia Acute Myeloid Leukemia (AML)1
1, 2Active Not RecruitingTreatmentGraft Versus Host Disease (GVHD) / Leukemias / Myelodysplastic Syndromes1
1, 2Active Not RecruitingTreatmentLeukemias1
1, 2Active Not RecruitingTreatmentLeukemias / Malignant Lymphomas / Small Intestine Cancer1
1, 2CompletedTreatmentAcute Lymphoblastic Leukaemias (ALL) / Acute Myelogenous Leukaemia (AML)1
1, 2CompletedTreatmentAcute Lymphoblastic Leukaemias (ALL) / Acute Myelogenous Leukaemia (AML) / Relapsed Leukemia1
1, 2CompletedTreatmentAcute Lymphoblastic Leukaemias (ALL) / Burkitt's Lymphoma / Lymphoma, Lymphoblastic1
1, 2CompletedTreatmentAdult Acute Myeloid Leukemia With 11q23 (MLL) Abnormalities / Adult Acute Myeloid Leukemia With Del(5q) / Adult Acute Myeloid Leukemia With Inv(16)(p13;q22) / Adult Acute Myeloid Leukemia With T(16;16)(p13;q22) / Adult Acute Myeloid Leukemia With T(8;21)(q22;q22) / Myelodysplastic Syndrome With Isolated Del(5q) / Previously Treated Myelodysplastic Syndromes / Recurrent Adult Acute Myeloid Leukemia1
1, 2CompletedTreatmentAdult Acute Myeloid Leukemia With 11q23 (MLL) Abnormalities / Adult Acute Myeloid Leukemia With Inv(16)(p13;q22) / Adult Acute Myeloid Leukemia With T(15;17)(q22;q12) / Adult Acute Myeloid Leukemia With T(16;16)(p13;q22) / Adult Acute Myeloid Leukemia With T(8;21)(q22;q22) / Adult Acute Promyelocytic Leukemia (M3) / Leukemia Acute Myeloid Leukemia (AML) / Recurrent Adult Acute Myeloid Leukemia1
1, 2CompletedTreatmentAdvanced Hematologic Malignancies / Leukemias / Myelodysplastic Syndrome1
1, 2CompletedTreatmentAnaplastic Large-Cell Lymphoma / Angioimmunoblastic T-Cell Lymphoma / Follicular Lymphoma (FL) / Low Grade B-cell Lymphoma, Not Otherwise Specified / Lymphoma, Large B-Cell, Diffuse (DLBCL) / Lymphoplasmacytic Lymphoma / Mantle Cell Lymphoma (MCL) / Marginal Zone Lymphoma / Peripheral T-Cell Lymphoma (PTCL) / Small Lymphocytic Lymphoma (SLL)1
1, 2CompletedTreatmentCancers / Chronic Myelomonocytic Leukemia1
1, 2CompletedTreatmentLeukemia Acute Myeloid Leukemia (AML) / Myelodysplasia1
1, 2CompletedTreatmentLeukemias3
1, 2CompletedTreatmentLymphoma, B-Cell / Non-Hodgkin's Lymphoma (NHL)1
1, 2CompletedTreatmentMyelodysplastic Syndrome1
1, 2RecruitingTreatmentAcute Lymphoblastic Leukaemias (ALL) / Acute Myelogenous Leukaemia (AML) / Burkitt Lymphoma/Leukemia / Lymphoma, Large B-Cell, Diffuse (DLBCL) / Lymphoma, Lymphoblastic1
1, 2RecruitingTreatmentMalignant Lymphomas1
1, 2TerminatedTreatmentAcute Myelogenous Leukaemia (AML)1
1, 2TerminatedTreatmentChronic Chronic myelogenous leukemia / Leukemias / Lymphoma, Hodgkins / Malignant Lymphomas / Multiple Myeloma (MM) / Myelodysplastic Syndrome1
1, 2TerminatedTreatmentMalignant Lymphomas1
1, 2TerminatedTreatmentMyelodysplastic Syndromes1
1, 2Unknown StatusTreatmentAcute Lymphoblastic Leukaemias (ALL)1
1, 2Unknown StatusTreatmentBlood And Marrow Transplantation / Leukemias / Lymphoma, Hodgkins / Malignant Lymphomas / Myelodysplastic Syndromes (MDS) / Non-Hodgkin's Lymphoma (NHL) / Transplantation Infection1
1, 2Unknown StatusTreatmentLeukemia Acute Myeloid Leukemia (AML)1
1, 2Unknown StatusTreatmentLeukemias / Myelodysplastic Syndromes1
2Active Not RecruitingTreatmentAcute Myeloid Leukemia Arising From Previous Myelodysplastic Syndrome / Acute, secondary Myeloid Leukemia / Adult Acute Lymphoblastic Leukemia in Remission / Adult Acute Megakaryoblastic Leukemia (M7) / Adult Acute Minimally Differentiated Myeloid Leukemia (M0) / Adult Acute Monoblastic Leukemia (M5a) / Adult Acute Monocytic Leukemia (M5b) / Adult Acute Myeloblastic Leukemia With Maturation (M2) / Adult Acute Myeloblastic Leukemia Without Maturation (M1) / Adult Acute Myeloid Leukemia in Remission / Adult Acute Myeloid Leukemia With 11q23 (MLL) Abnormalities / Adult Acute Myeloid Leukemia With Del(5q) / Adult Acute Myeloid Leukemia With Inv(16)(p13;q22) / Adult Acute Myeloid Leukemia With T(16;16)(p13;q22) / Adult Acute Myeloid Leukemia With T(8;21)(q22;q22) / Adult Acute Myelomonocytic Leukemia (M4) / Adult Erythroleukemia (M6a) / Adult Pure Erythroid Leukemia (M6b) / Chronic Myelomonocytic Leukemia / Myelodysplastic Syndrome / Previously Treated Myelodysplastic Syndromes / Secondary Acute Myeloid Leukemia in Remission / Secondary Myelodysplastic Syndromes / Therapy-Related Myelodysplastic Syndrome1
2Active Not RecruitingTreatmentLeukemias1
2Active Not RecruitingTreatmentLeukemias / Malignant Lymphomas / Transplantation, Stem Cell1
2Active Not RecruitingTreatmentLymphoma, Lymphoblastic1
2CompletedDiagnosticLeukemia Acute Myeloid Leukemia (AML) / Myelodysplastic Syndrome1
2CompletedTreatmentAcute Lymphoblastic Leukaemias (ALL)4
2CompletedTreatmentAcute Lymphoblastic Leukaemias (ALL) / Allogeneic Haematopoietic Stem Cell Transplantation / Leukemias / Malignant Lymphomas1
2CompletedTreatmentAcute Lymphoblastic Leukaemias (ALL) / Leukemia Acute Myeloid Leukemia (AML) / Myelodysplastic Syndrome1
2CompletedTreatmentAcute Lymphocytic Leukemia (ALL) / Acute Myelogenous Leukaemia (AML) / Chronic Chronic myelogenous leukemia1
2CompletedTreatmentAcute Myelogenous Leukaemia (AML)1
2CompletedTreatmentAcute Myelogenous Leukaemia (AML) / Leukemia Acute Myeloid Leukemia (AML)1
2CompletedTreatmentAcute Myelogenous Leukaemia (AML) / Chronic Chronic myelogenous leukemia / Myelodysplastic Syndromes1
2CompletedTreatmentAdrenoleukodystrophy / Gangliosidosis, GM1 / I-Cell Disease / Leukodystrophy, Globoid Cell / Metachromatic Leukodystrophy / Sandhoffs Disease / Sanfilippo Syndrome / Tay Sachs Disease / Wolman's Disease1
2CompletedTreatmentAdult Acute Myeloid Leukemia With 11q23 (MLL) Abnormalities / Adult Acute Myeloid Leukemia With Del(5q) / Adult Acute Myeloid Leukemia With Inv(16)(p13;q22) / Adult Acute Myeloid Leukemia With T(15;17)(q22;q12) / Adult Acute Myeloid Leukemia With T(16;16)(p13;q22) / Adult Acute Myeloid Leukemia With T(8;21)(q22;q22) / Chronic Myelomonocytic Leukemia / De Novo Myelodysplastic Syndromes / Myeloproliferative Neoplasm With 10% Blasts or Higher / Refractory Anemia With Excess Blasts / Untreated Adult Acute Myeloid Leukemia1
2CompletedTreatmentChronic Myeloid Leukemia (CML) / Leukemia Acute Myeloid Leukemia (AML) / Myelodysplastic Syndrome2
2CompletedTreatmentChronic Myelomonocytic Leukemia / Myelodysplastic Syndrome1
2CompletedTreatmentLeukemia Acute Myeloid Leukemia (AML)5
2CompletedTreatmentLeukemia Acute Myeloid Leukemia (AML) / Myelodysplastic Syndrome1
2CompletedTreatmentLeukemia, Lymphoblastic, Acute, Pediatric1
2CompletedTreatmentLeukemia, Myelocytic, Acute, Pediatric1
2CompletedTreatmentLeukemias5
2CompletedTreatmentLeukemias / Myelodysplastic Syndrome1
2CompletedTreatmentLeukemias / Myeloproliferative Disorders1
2CompletedTreatmentMyelodysplastic Syndrome1
2CompletedTreatmentMyelodysplastic Syndromes / Myeloid Leukemias1
2CompletedTreatmentMyelodysplastic Syndromes / Secondary AML1
2CompletedTreatmentNon-Hodgkin's Lymphoma (NHL)1
2Not Yet RecruitingTreatmentGraft Versus Host Disease (GVHD)1
2RecruitingTreatmentAcute Lymphoblastic Leukaemias (ALL) / Acute Myelogenous Leukaemia (AML) / Multiple Myeloma (MM) / Myelodysplastic Syndrome1
2RecruitingTreatmentAcute Lymphoblastic Leukaemias (ALL) / Burkitt Leukemia/Lymphoma / Hematopoietic/Lymphoid Cancer / Lymphoma, Lymphoblastic1
2RecruitingTreatmentAcute Lymphoblastic Leukaemias (ALL) / Leukemia Acute Myeloid Leukemia (AML)1
2RecruitingTreatmentAcute Lymphocytic Leukemia (ALL) / Chronic Lymphocytic Leukaemia (CLL) / Chronic Myeloid Leukemia (CML) / Leukemia Acute Myeloid Leukemia (AML) / Lymphoma, Hodgkins / Non-Hodgkin's Lymphoma (NHL)1
2RecruitingTreatmentHematopoietic/Lymphoid Cancer1
2RecruitingTreatmentLangerhans Cell Histiocytosis (LCH)1
2RecruitingTreatmentLeukemia Acute Myeloid Leukemia (AML)1
2RecruitingTreatmentLeukemias1
2RecruitingTreatmentLeukemias / Malignant Lymphomas / Myeloproliferative Disorders / Plasma Cell Myeloma1
2RecruitingTreatmentNon-malignant Hematologic Disorders1
2RecruitingTreatmentRecurrent B-Cell Childhood Acute Lymphoblastic Leukemia / Recurrent Childhood B-Lymphoblastic Lymphoma1
2TerminatedTreatmentAcute Lymphoblastic Leukaemias (ALL) / Acute Myelocytic Leukemia / Chronic Myeloid Leukemia (CML) / Granulocytic Sarcoma / Hodgkin's or Non-Hodgkin's Lymphoma / Juvenile Myelomonocytic Leukemia / Myelodysplastic Syndrome1
2TerminatedTreatmentAcute Lymphoblastic Leukaemias (ALL) / Leukemia, B-Cell / Leukemia, T-Cell / Non-Hodgkin's Lymphoma (NHL)1
2TerminatedTreatmentAcute Lymphoblastic Leukaemias (ALL) / Leukemia, Myelogenous, Acute / Minimal Residual Disease1
2TerminatedTreatmentAcute Lymphocytic Leukemia (ALL) / Acute Myelogenous Leukaemia (AML) / Aplastic Anaemia (AA) / Chronic Chronic myelogenous leukemia / Chronic Lymphocytic Leukaemia (CLL) / Hodgkins Disease (HD) / Multiple Myeloma (MM) / Myelodysplastic Syndrome / Non-Hodgkin's Lymphoma (NHL)1
2TerminatedTreatmentAcute Myelogenous Leukaemia (AML)1
2TerminatedTreatmentAdult Acute Myeloid Leukemia in Remission / Adult Acute Myeloid Leukemia With 11q23 (MLL) Abnormalities / Adult Acute Myeloid Leukemia With Inv(16)(p13;q22) / Adult Acute Myeloid Leukemia With T(15;17)(q22;q12) / Adult Acute Myeloid Leukemia With T(16;16)(p13;q22) / Adult Acute Myeloid Leukemia With T(8;21)(q22;q22) / Recurrent Adult Acute Myeloid Leukemia1
2TerminatedTreatmentCancers1
2TerminatedTreatmentLeukemia Acute Myeloid Leukemia (AML)1
2TerminatedTreatmentLeukemia Acute Myeloid Leukemia (AML) / Myelodysplastic Syndromes1
2TerminatedTreatmentLeukemias1
2TerminatedTreatmentMultiple Myeloma (MM)1
2TerminatedTreatmentMyelodysplastic Syndromes1
2TerminatedTreatmentOsteopetrosis1
2TerminatedTreatmentAcute, relapsed Myelogenous Leukemia1
2Unknown StatusTreatmentLeukemia Acute Myeloid Leukemia (AML) / Smith-Magenis Syndrome1
2WithdrawnTreatmentAcute Lymphoblastic Leukaemias (ALL) / Leukemia Acute Myeloid Leukemia (AML)1
2WithdrawnTreatmentLangerhans Cell Histiocytosis (LCH)1
2, 3CompletedTreatmentLeukemia, Acute1
2, 3CompletedTreatmentLeukemias / Myelodysplastic Syndromes1
2, 3RecruitingTreatmentAcute Lymphoblastic Leukaemias (ALL) / Acute Lymphoblastic Lymphoma1
2, 3RecruitingTreatmentLeukemias1
3Active Not RecruitingTreatmentAcute Lymphoblastic Leukaemias (ALL)1
3Active Not RecruitingTreatmentAcute Myeloid Leukemia With Multilineage Dysplasia Following Myelodysplastic Syndrome / Acute, secondary Myeloid Leukemia / Adult Acute Megakaryoblastic Leukemia (M7) / Adult Acute Minimally Differentiated Myeloid Leukemia (M0) / Adult Acute Monoblastic Leukemia (M5a) / Adult Acute Monocytic Leukemia (M5b) / Adult Acute Myeloblastic Leukemia With Maturation (M2) / Adult Acute Myeloblastic Leukemia Without Maturation (M1) / Adult Acute Myeloid Leukemia With 11q23 (MLL) Abnormalities / Adult Acute Myeloid Leukemia With Del(5q) / Adult Acute Myeloid Leukemia With Inv(16)(p13;q22) / Adult Acute Myeloid Leukemia With T(16;16)(p13;q22) / Adult Acute Myeloid Leukemia With T(8;21)(q22;q22) / Adult Acute Myelomonocytic Leukemia (M4) / Adult Erythroleukemia (M6a) / Adult Pure Erythroid Leukemia (M6b) / Untreated Adult Acute Myeloid Leukemia1
3Active Not RecruitingTreatmentDisorder Related to Bone Marrow Transplantation / Leukemias / Transplantation Infection1
3Active Not RecruitingTreatmentLeukemia Acute Myeloid Leukemia (AML)1
3CompletedTreatmentAcute Myelogenous Leukaemia (AML)1
3RecruitingTreatmentAcute Lymphoblastic Leukaemias (ALL) / B Acute Lymphoblastic Leukemia / Central Nervous System Leukemia / Cognitive Side Effects of Cancer Therapy / Neurotoxicity Syndrome / Osteonecrosis / Pain / Ph-Like Acute Lymphoblastic Leukemia / Testicular Leukemia / Therapy-Related Toxicity / Untreated Adult Acute Lymphoblastic Leukemia / Untreated Childhood Acute Lymphoblastic Leukemia1
3RecruitingTreatmentB Acute Lymphoblastic Leukemia / Central Nervous System Leukemia / Cognitive Side Effects of Cancer Therapy / Neurotoxicity Syndrome / Osteonecrosis / Pain / Testicular Leukemia / Therapy-Related Toxicity / Untreated Adult Acute Lymphoblastic Leukemia / Untreated Childhood Acute Lymphoblastic Leukemia1
3RecruitingTreatmentLeukemias1
Not AvailableCompletedTreatmentLeukemia Acute Myeloid Leukemia (AML)1
Not AvailableCompletedTreatmentLysosomal Storage Diseases / Peroxisomal Disorders1
Not AvailableSuspendedTreatmentBone Marrow Failure Syndromes / Congenital Immunodeficiency / Metabolic Diseases / Myeloid Malignancy / Severe Immune Dysregulation / Transfusion-dependent Red Blood Cell (RBC) Defect1

Pharmacoeconomics

Manufacturers
  • Genzyme corp
Packagers
  • AAIPharma Inc.
  • Genzyme Inc.
Dosage forms
FormRouteStrength
InjectionIntravenous1 mg/1mL
SolutionIntravenous1 mg
Injection, solution, concentrateIntravenous1 mg/ml
Prices
Unit descriptionCostUnit
Clolar 20 mg/20 ml vial135.0USD ml
DrugBank does not sell nor buy drugs. Pricing information is supplied for informational purposes only.
Patents
Patent NumberPediatric ExtensionApprovedExpires (estimated)
CA2102782No2003-09-162012-05-07Canada
US5661136Yes1998-07-142018-07-14Us

Properties

State
Solid
Experimental Properties
PropertyValueSource
logP0Not Available
Predicted Properties
PropertyValueSource
Water Solubility4.89 mg/mLALOGPS
logP0.32ALOGPS
logP-0.29ChemAxon
logS-1.8ALOGPS
pKa (Strongest Acidic)12.71ChemAxon
pKa (Strongest Basic)1.3ChemAxon
Physiological Charge0ChemAxon
Hydrogen Acceptor Count7ChemAxon
Hydrogen Donor Count3ChemAxon
Polar Surface Area119.31 Å2ChemAxon
Rotatable Bond Count2ChemAxon
Refractivity67 m3·mol-1ChemAxon
Polarizability26.06 Å3ChemAxon
Number of Rings3ChemAxon
Bioavailability1ChemAxon
Rule of FiveYesChemAxon
Ghose FilterYesChemAxon
Veber's RuleNoChemAxon
MDDR-like RuleNoChemAxon
Predicted ADMET features
PropertyValueProbability
Human Intestinal Absorption+1.0
Blood Brain Barrier+0.9827
Caco-2 permeable-0.7369
P-glycoprotein substrateNon-substrate0.8001
P-glycoprotein inhibitor INon-inhibitor0.9382
P-glycoprotein inhibitor IINon-inhibitor0.8279
Renal organic cation transporterNon-inhibitor0.9144
CYP450 2C9 substrateNon-substrate0.9031
CYP450 2D6 substrateNon-substrate0.8291
CYP450 3A4 substrateNon-substrate0.5681
CYP450 1A2 substrateNon-inhibitor0.817
CYP450 2C9 inhibitorNon-inhibitor0.8462
CYP450 2D6 inhibitorNon-inhibitor0.8849
CYP450 2C19 inhibitorNon-inhibitor0.8391
CYP450 3A4 inhibitorNon-inhibitor0.8499
CYP450 inhibitory promiscuityLow CYP Inhibitory Promiscuity0.9002
Ames testNon AMES toxic0.7338
CarcinogenicityNon-carcinogens0.7723
BiodegradationNot ready biodegradable1.0
Rat acute toxicity2.2651 LD50, mol/kg Not applicable
hERG inhibition (predictor I)Weak inhibitor0.9643
hERG inhibition (predictor II)Non-inhibitor0.8304
ADMET data is predicted using admetSAR, a free tool for evaluating chemical ADMET properties. (23092397)

Spectra

Mass Spec (NIST)
Not Available
Spectra
SpectrumSpectrum TypeSplash Key
Predicted GC-MS Spectrum - GC-MSPredicted GC-MSNot Available
Predicted MS/MS Spectrum - 10V, Positive (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 20V, Positive (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 40V, Positive (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 10V, Negative (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 20V, Negative (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 40V, Negative (Annotated)Predicted LC-MS/MSNot Available
LC-MS/MS Spectrum - LC-ESI-qTof , PositiveLC-MS/MSNot Available
MS/MS Spectrum - , positiveLC-MS/MSsplash10-00di-1903000000-294bd193e470f829e963

Taxonomy

Description
This compound belongs to the class of organic compounds known as purine 2'-deoxyribonucleosides. These are compounds consisting of a purine linked to a ribose which lacks a hydroxyl group at position 2.
Kingdom
Organic compounds
Super Class
Nucleosides, nucleotides, and analogues
Class
Purine nucleosides
Sub Class
Purine 2'-deoxyribonucleosides
Direct Parent
Purine 2'-deoxyribonucleosides
Alternative Parents
6-aminopurines / 2-halopyrimidines / Aminopyrimidines and derivatives / Aryl chlorides / Imidolactams / N-substituted imidazoles / Heteroaromatic compounds / Tetrahydrofurans / Secondary alcohols / Fluorohydrins
show 9 more
Substituents
Purine 2'-deoxyribonucleoside / 6-aminopurine / Imidazopyrimidine / Purine / Aminopyrimidine / 2-halopyrimidine / Halopyrimidine / Aryl chloride / Aryl halide / N-substituted imidazole
show 28 more
Molecular Framework
Aromatic heteropolycyclic compounds
External Descriptors
organofluorine compound, adenosines (CHEBI:681569)

Targets

Kind
Protein
Organism
Human
Pharmacological action
Yes
Actions
Inhibitor
General Function
Protein kinase binding
Specific Function
Plays an essential role in the initiation of DNA replication. During the S phase of the cell cycle, the DNA polymerase alpha complex (composed of a catalytic subunit POLA1/p180, a regulatory subuni...
Gene Name
POLA1
Uniprot ID
P09884
Uniprot Name
DNA polymerase alpha catalytic subunit
Molecular Weight
165911.405 Da
References
  1. Overington JP, Al-Lazikani B, Hopkins AL: How many drug targets are there? Nat Rev Drug Discov. 2006 Dec;5(12):993-6. [PubMed:17139284]
  2. Imming P, Sinning C, Meyer A: Drugs, their targets and the nature and number of drug targets. Nat Rev Drug Discov. 2006 Oct;5(10):821-34. [PubMed:17016423]
  3. Pession A, Masetti R, Kleinschmidt K, Martoni A: Use of clofarabine for acute childhood leukemia. Biologics. 2010 Jun 24;4:111-8. [PubMed:20631817]
  4. Authors unspecified: Clofarabine. Drugs R D. 2004;5(4):213-7. [PubMed:15230627]
  5. Musto P, Ferrara F: Clofarabine: in search of combinations for the treatment of patients with high-risk acute myeloid leukemia. Cancer. 2008 Oct 15;113(8):1995-8. doi: 10.1002/cncr.23804. [PubMed:18780321]
  6. Harned TM, Gaynon PS: Treating refractory leukemias in childhood, role of clofarabine. Ther Clin Risk Manag. 2008 Apr;4(2):327-36. [PubMed:18728851]
  7. Kantarjian HM, Jeha S, Gandhi V, Wess M, Faderl S: Clofarabine: past, present, and future. Leuk Lymphoma. 2007 Oct;48(10):1922-30. [PubMed:17852710]
  8. Lech-Maranda E, Korycka A, Robak T: Clofarabine as a novel nucleoside analogue approved to treat patients with haematological malignancies: mechanism of action and clinical activity. Mini Rev Med Chem. 2009 Jun;9(7):805-12. [PubMed:19519505]
  9. Zhenchuk A, Lotfi K, Juliusson G, Albertioni F: Mechanisms of anti-cancer action and pharmacology of clofarabine. Biochem Pharmacol. 2009 Dec 1;78(11):1351-9. doi: 10.1016/j.bcp.2009.06.094. Epub 2009 Jul 1. [PubMed:19576186]
Kind
Protein
Organism
Human
Pharmacological action
Yes
Actions
Inhibitor
General Function
Ribonucleoside-diphosphate reductase activity, thioredoxin disulfide as acceptor
Specific Function
Provides the precursors necessary for DNA synthesis. Catalyzes the biosynthesis of deoxyribonucleotides from the corresponding ribonucleotides.
Gene Name
RRM1
Uniprot ID
P23921
Uniprot Name
Ribonucleoside-diphosphate reductase large subunit
Molecular Weight
90069.375 Da
References
  1. Overington JP, Al-Lazikani B, Hopkins AL: How many drug targets are there? Nat Rev Drug Discov. 2006 Dec;5(12):993-6. [PubMed:17139284]
  2. Imming P, Sinning C, Meyer A: Drugs, their targets and the nature and number of drug targets. Nat Rev Drug Discov. 2006 Oct;5(10):821-34. [PubMed:17016423]
  3. Pession A, Masetti R, Kleinschmidt K, Martoni A: Use of clofarabine for acute childhood leukemia. Biologics. 2010 Jun 24;4:111-8. [PubMed:20631817]
  4. Authors unspecified: Clofarabine. Drugs R D. 2004;5(4):213-7. [PubMed:15230627]
  5. Musto P, Ferrara F: Clofarabine: in search of combinations for the treatment of patients with high-risk acute myeloid leukemia. Cancer. 2008 Oct 15;113(8):1995-8. doi: 10.1002/cncr.23804. [PubMed:18780321]
  6. Harned TM, Gaynon PS: Treating refractory leukemias in childhood, role of clofarabine. Ther Clin Risk Manag. 2008 Apr;4(2):327-36. [PubMed:18728851]
  7. Kantarjian HM, Jeha S, Gandhi V, Wess M, Faderl S: Clofarabine: past, present, and future. Leuk Lymphoma. 2007 Oct;48(10):1922-30. [PubMed:17852710]
  8. Lech-Maranda E, Korycka A, Robak T: Clofarabine as a novel nucleoside analogue approved to treat patients with haematological malignancies: mechanism of action and clinical activity. Mini Rev Med Chem. 2009 Jun;9(7):805-12. [PubMed:19519505]
  9. Zhenchuk A, Lotfi K, Juliusson G, Albertioni F: Mechanisms of anti-cancer action and pharmacology of clofarabine. Biochem Pharmacol. 2009 Dec 1;78(11):1351-9. doi: 10.1016/j.bcp.2009.06.094. Epub 2009 Jul 1. [PubMed:19576186]
3. DNA
Kind
Nucleotide
Organism
Human
Pharmacological action
Yes
Actions
Other/unknown
General Function:
Used for biological information storage.
Specific Function:
DNA contains the instructions needed for an organism to develop, survive and reproduce.
Molecular Weight:
2.15 x 1012 Da
References
  1. Pession A, Masetti R, Kleinschmidt K, Martoni A: Use of clofarabine for acute childhood leukemia. Biologics. 2010 Jun 24;4:111-8. [PubMed:20631817]
  2. Harned TM, Gaynon PS: Treating refractory leukemias in childhood, role of clofarabine. Ther Clin Risk Manag. 2008 Apr;4(2):327-36. [PubMed:18728851]

Enzymes

Kind
Protein
Organism
Human
Pharmacological action
Unknown
Actions
Substrate
General Function
Protein homodimerization activity
Specific Function
Required for the phosphorylation of the deoxyribonucleosides deoxycytidine (dC), deoxyguanosine (dG) and deoxyadenosine (dA). Has broad substrate specificity, and does not display selectivity based...
Gene Name
DCK
Uniprot ID
P27707
Uniprot Name
Deoxycytidine kinase
Molecular Weight
30518.315 Da
References
  1. Pession A, Masetti R, Kleinschmidt K, Martoni A: Use of clofarabine for acute childhood leukemia. Biologics. 2010 Jun 24;4:111-8. [PubMed:20631817]
  2. Zhenchuk A, Lotfi K, Juliusson G, Albertioni F: Mechanisms of anti-cancer action and pharmacology of clofarabine. Biochem Pharmacol. 2009 Dec 1;78(11):1351-9. doi: 10.1016/j.bcp.2009.06.094. Epub 2009 Jul 1. [PubMed:19576186]
  3. Kantarjian HM, Jeha S, Gandhi V, Wess M, Faderl S: Clofarabine: past, present, and future. Leuk Lymphoma. 2007 Oct;48(10):1922-30. [PubMed:17852710]

Transporters

Kind
Protein
Organism
Human
Pharmacological action
Unknown
Actions
Substrate
General Function
Xenobiotic-transporting atpase activity
Specific Function
High-capacity urate exporter functioning in both renal and extrarenal urate excretion. Plays a role in porphyrin homeostasis as it is able to mediates the export of protoporhyrin IX (PPIX) both fro...
Gene Name
ABCG2
Uniprot ID
Q9UNQ0
Uniprot Name
ATP-binding cassette sub-family G member 2
Molecular Weight
72313.47 Da
References
  1. de Wolf C, Jansen R, Yamaguchi H, de Haas M, van de Wetering K, Wijnholds J, Beijnen J, Borst P: Contribution of the drug transporter ABCG2 (breast cancer resistance protein) to resistance against anticancer nucleosides. Mol Cancer Ther. 2008 Sep;7(9):3092-102. doi: 10.1158/1535-7163.MCT-08-0427. Epub 2008 Sep 2. [PubMed:18765824]

Drug created on June 13, 2005 07:24 / Updated on September 22, 2018 22:24