Identification

Name
Cladribine
Accession Number
DB00242  (APRD00260)
Type
Small Molecule
Groups
Approved, Investigational
Description

An antineoplastic agent used in the treatment of lymphoproliferative diseases including hairy-cell leukemia. [PubChem]

Structure
Thumb
Synonyms
  • (2R,3S,5R)-5-(6-amino-2-Chloropurin-9-yl)-2-(hydroxymethyl)oxolan-3-ol
  • 2-CdA
  • 2-Chloro-2'-deoxy-beta-adenosine
  • 2-Chloro-2'-deoxyadenosine
  • 2-chloro-6-amino-9-(2-Deoxy-beta-D-erythro-pentofuranosyl)purine
  • 2-chloro-Deoxyadenosine
  • 2-Chlorodeoxyadenosine
  • 2ClAdo
  • Cladribina
  • Cladribine
  • Cladribinum
  • CldAdo
External IDs
RWJ 26251 / RWJ-26251
Prescription Products
NameDosageStrengthRouteLabellerMarketing StartMarketing End
Cladribine InjectionSolution1 mgIntravenousFresenius Kabi2009-06-30Not applicableCanada
Leustatin 1mg/mlSolution1 mgIntravenousJanssen Pharmaceuticals1993-12-312011-12-19Canada
Generic Prescription Products
NameDosageStrengthRouteLabellerMarketing StartMarketing End
CladribineInjection1 mg/mLIntravenousMylan Institutional2011-07-10Not applicableUs
CladribineInjection1 mg/mLIntravenousPfizer Laboratories Div Pfizer Inc.2011-07-10Not applicableUs
CladribineInjection1 mg/mLIntravenousMylan Institutional2011-10-07Not applicableUs
CladribineInjection1 mg/mLIntravenousPfizer Laboratories Div Pfizer Inc.2011-10-07Not applicableUs
CladribineInjection1 mg/mLIntravenousFresenius Kabi2004-12-01Not applicableUs
International/Other Brands
Leustatin / Litak / Movectro / Mylinax
Categories
UNII
47M74X9YT5
CAS number
4291-63-8
Weight
Average: 285.687
Monoisotopic: 285.062866982
Chemical Formula
C10H12ClN5O3
InChI Key
PTOAARAWEBMLNO-KVQBGUIXSA-N
InChI
InChI=1S/C10H12ClN5O3/c11-10-14-8(12)7-9(15-10)16(3-13-7)6-1-4(18)5(2-17)19-6/h3-6,17-18H,1-2H2,(H2,12,14,15)/t4-,5+,6+/m0/s1
IUPAC Name
(2R,3S,5R)-5-(6-amino-2-chloro-9H-purin-9-yl)-2-(hydroxymethyl)oxolan-3-ol
SMILES
NC1=C2N=CN([[email protected]]3C[[email protected]](O)[[email protected]@H](CO)O3)C2=NC(Cl)=N1

Pharmacology

Indication

For the treatment of active hairy cell leukemia (leukemic reticuloendotheliosis) as defined by clinically significant anemia, neutropenia, thrombocytopenia, or disease-related symptoms. Also used as an alternative agent for the treatment of chronic lymphocytic leukemia (CLL), low-grade non-Hodgkin's lymphoma, and cutaneous T-cell lymphoma.

Structured Indications
Not Available
Pharmacodynamics

Cladribine is a synthetic purine nucleoside that acts as an antineoplastic agent with immunosuppressive effects. Cladribine differs structurally from deoxyadenosine only by the presence of a chlorine atom at position 2 of the purine ring, which results in resistance to enzymatic degradation by adenosine deaminase. Due to this resistance, cladribine exhibits a more prolonged cytotoxic effect than deoxyadenosine against resting and proliferating lymphocytes. Cladribine is one of a group of chemotherapy drugs known as the anti-metabolites. Anti-metabolites stop cells from making and repairing DNA, which are processes that are necessary for cancer cells to grow and multiply.

Mechanism of action

Cladribine is structurally related to fludarabine and pentostatin but has a different mechanism of action. Although the exact mechanism of action has not been fully determined, evidence shows that cladribine is phosphorylated by deoxycytidine kinase to the nucleotidecladribine triphosphate (CdATP; 2-chloro-2′-deoxyadenosine 5′-triphosphate), which accumulates and is incorporated into DNA in cells such as lymphocytes that contain high levels of deoxycytidine kinase and low levels of deoxynucleotidase, resulting in DNA strand breakage and inhibition of DNA synthesis and repair. High levels of CdATP also appear to inhibit ribonucleotide reductase, which leads to an imbalance in triphosphorylated deoxynucleotide (dNTP) pools and subsequent DNA strand breaks, inhibition of DNA synthesis and repair, nicotinamide adenine dinucleotide (NAD) and ATP depletion, and cell death. Unlike other antimetabolite drugs, cladribine has cytotoxic effects on resting as well as proliferating lymphocytes. However, it does cause cells to accumulate at the G1/S phase junction, suggesting that cytotoxicity is associated with events critical to cell entry into S phase. It also binds purine nucleoside phosphorylase (PNP), however no relationship between this binding and a mechanism of action has been established.

TargetActionsOrganism
ARibonucleoside-diphosphate reductase large subunit
inhibitor
Human
ARibonucleoside-diphosphate reductase subunit M2
inhibitor
Human
ARibonucleoside-diphosphate reductase subunit M2 B
inhibitor
Human
ADNA
other/unknown
Human
ADNA polymerase alpha catalytic subunit
inhibitor
Human
ADNA polymerase epsilon catalytic subunit A
inhibitor
Human
ADNA polymerase epsilon subunit 2
inhibitor
Human
ADNA polymerase epsilon subunit 3
inhibitor
Human
ADNA polymerase epsilon subunit 4
inhibitor
Human
APurine nucleoside phosphorylase
inducer
Human
Absorption

Oral bioavailability is 34 to 48%.

Volume of distribution
  • 4.5 ± 2.8 L/kg [patients with hematologic malignancies]
  • 9 L/kg
Protein binding

20%

Metabolism

Metabolized in all cells with deoxycytidine kinase activity to 2-chloro-2'-deoxyadenosine-5'-triphosphate

Route of elimination
Not Available
Half life

5.4 hours

Clearance
  • 978 +/- 422 mL/h/kg
Toxicity

Symptoms of overdose include irreversible neurologic toxicity (paraparesis/quadriparesis), acute nephrotoxicity, and severe bone marrow suppression resulting in neutropenia, anemia and thrombocytopenia.

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

Interactions

Drug Interactions
DrugInteractionDrug group
AcetyldigitoxinAcetyldigitoxin may decrease the cardiotoxic activities of Cladribine.Approved
AcetyldigoxinAcetyldigoxin may decrease the cardiotoxic activities of Cladribine.Experimental
BCG vaccineThe therapeutic efficacy of BCG vaccine can be decreased when used in combination with Cladribine.Investigational
BevacizumabBevacizumab may increase the cardiotoxic activities of Cladribine.Approved, Investigational
BupropionThe serum concentration of Cladribine can be increased when it is combined with Bupropion.Approved
CabazitaxelThe risk or severity of adverse effects can be increased when Cabazitaxel is combined with Cladribine.Approved
Clostridium tetani toxoid antigen (formaldehyde inactivated)The therapeutic efficacy of Clostridium tetani toxoid antigen (formaldehyde inactivated) can be decreased when used in combination with Cladribine.Approved
ClozapineThe risk or severity of adverse effects can be increased when Cladribine is combined with Clozapine.Approved
Corynebacterium diphtheriae toxoid antigen (formaldehyde inactivated)The therapeutic efficacy of Corynebacterium diphtheriae toxoid antigen (formaldehyde inactivated) can be decreased when used in combination with Cladribine.Approved
CyclophosphamideCyclophosphamide may increase the cardiotoxic activities of Cladribine.Approved, Investigational
CymarinCymarin may decrease the cardiotoxic activities of Cladribine.Experimental
DenosumabThe risk or severity of adverse effects can be increased when Denosumab is combined with Cladribine.Approved
DeslanosideDeslanoside may decrease the cardiotoxic activities of Cladribine.Approved
DigitoxinDigitoxin may decrease the cardiotoxic activities of Cladribine.Approved, Investigational
DigoxinDigoxin may decrease the cardiotoxic activities of Cladribine.Approved
Digoxin Immune Fab (Ovine)Digoxin Immune Fab (Ovine) may decrease the cardiotoxic activities of Cladribine.Approved
DocetaxelThe risk or severity of adverse effects can be increased when Docetaxel is combined with Cladribine.Approved, Investigational
EltrombopagThe serum concentration of Cladribine can be increased when it is combined with Eltrombopag.Approved
FingolimodCladribine may increase the immunosuppressive activities of Fingolimod.Approved, Investigational
G17DTThe therapeutic efficacy of G17DT can be decreased when used in combination with Cladribine.Investigational
GI-5005The therapeutic efficacy of GI-5005 can be decreased when used in combination with Cladribine.Investigational
GitoformateGitoformate may decrease the cardiotoxic activities of Cladribine.Experimental
Hepatitis A VaccineThe therapeutic efficacy of Hepatitis A Vaccine can be decreased when used in combination with Cladribine.Approved
Hepatitis B Vaccine (Recombinant)The therapeutic efficacy of Hepatitis B Vaccine (Recombinant) can be decreased when used in combination with Cladribine.Approved, Withdrawn
INGN 201The therapeutic efficacy of INGN 201 can be decreased when used in combination with Cladribine.Investigational
INGN 225The therapeutic efficacy of INGN 225 can be decreased when used in combination with Cladribine.Investigational
Lanatoside CLanatoside C may decrease the cardiotoxic activities of Cladribine.Experimental
LeflunomideThe risk or severity of adverse effects can be increased when Cladribine is combined with Leflunomide.Approved, Investigational
MetamizoleThe risk or severity of adverse effects can be increased when Metamizole is combined with Cladribine.Investigational, Withdrawn
MetildigoxinMetildigoxin may decrease the cardiotoxic activities of Cladribine.Experimental
NatalizumabThe risk or severity of adverse effects can be increased when Cladribine is combined with Natalizumab.Approved, Investigational
OleandrinOleandrin may decrease the cardiotoxic activities of Cladribine.Experimental, Investigational
OuabainOuabain may decrease the cardiotoxic activities of Cladribine.Approved
PaclitaxelThe risk or severity of adverse effects can be increased when Paclitaxel is combined with Cladribine.Approved, Vet Approved
PeruvosidePeruvoside may decrease the cardiotoxic activities of Cladribine.Experimental
PimecrolimusThe risk or severity of adverse effects can be increased when Pimecrolimus is combined with Cladribine.Approved, Investigational
ProscillaridinProscillaridin may decrease the cardiotoxic activities of Cladribine.Experimental
Rabies virus inactivated antigen, AThe risk or severity of adverse effects can be increased when Cladribine is combined with Rabies virus inactivated antigen, A.Approved
Rabies virus inactivated antigen, AThe therapeutic efficacy of Rabies virus inactivated antigen, A can be decreased when used in combination with Cladribine.Approved
RindopepimutThe therapeutic efficacy of Rindopepimut can be decreased when used in combination with Cladribine.Investigational
RoflumilastRoflumilast may increase the immunosuppressive activities of Cladribine.Approved
RolapitantThe serum concentration of Cladribine can be increased when it is combined with Rolapitant.Approved
Rotavirus VaccineThe therapeutic efficacy of Rotavirus Vaccine can be decreased when used in combination with Cladribine.Approved
Rubella virus vaccineThe therapeutic efficacy of Rubella virus vaccine can be decreased when used in combination with Cladribine.Approved
Salmonella typhi ty21a live antigenThe therapeutic efficacy of Salmonella typhi ty21a live antigen can be decreased when used in combination with Cladribine.Approved
Sipuleucel-TThe therapeutic efficacy of Sipuleucel-T can be decreased when used in combination with Cladribine.Approved
SRP 299The therapeutic efficacy of SRP 299 can be decreased when used in combination with Cladribine.Investigational
TacrolimusThe risk or severity of adverse effects can be increased when Tacrolimus is combined with Cladribine.Approved, Investigational
TecemotideThe therapeutic efficacy of Tecemotide can be decreased when used in combination with Cladribine.Investigational
TeriflunomideThe serum concentration of Cladribine can be increased when it is combined with Teriflunomide.Approved
TG4010The therapeutic efficacy of TG4010 can be decreased when used in combination with Cladribine.Investigational
TofacitinibCladribine may increase the immunosuppressive activities of Tofacitinib.Approved, Investigational
TrastuzumabTrastuzumab may increase the cardiotoxic activities of Cladribine.Approved, Investigational
Yellow fever vaccineThe therapeutic efficacy of Yellow fever vaccine can be decreased when used in combination with Cladribine.Approved
Zoster vaccineThe therapeutic efficacy of Zoster vaccine can be decreased when used in combination with Cladribine.Approved
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

Synthesis Reference

Szepsel Gerszberg, "Method for the production of 2-chloro-2' -deoxyadenosine (cladribine) and its 3,5-di-O-p-toluoyl derivative." U.S. Patent US20020052491, issued May 02, 2002.

US20020052491
General References
  1. Warnke C, Wiendl H, Hartung HP, Stuve O, Kieseier BC: Identification of targets and new developments in the treatment of multiple sclerosis--focus on cladribine. Drug Des Devel Ther. 2010 Jul 21;4:117-26. [PubMed:20689698]
  2. Sigal DS, Miller HJ, Schram ED, Saven A: Beyond hairy cell: the activity of cladribine in other hematologic malignancies. Blood. 2010 Oct 21;116(16):2884-96. doi: 10.1182/blood-2010-02-246140. Epub 2010 Jul 15. [PubMed:20634380]
  3. Khalid BA, Hamilton NT, Cauchi MN: Binding of thyroid microsomes by lymphocytes from patients with thyroid disease and normal subjects. Clin Exp Immunol. 1976 Jan;23(1):28-32. [PubMed:1261088]
  4. Sampat K, Kantarjian H, Borthakur G: Clofarabine: emerging role in leukemias. Expert Opin Investig Drugs. 2009 Oct;18(10):1559-64. doi: 10.1517/13543780903173222. [PubMed:19715446]
  5. 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]
  6. 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]
  7. 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]
External Links
Human Metabolome Database
HMDB14387
KEGG Drug
D01370
PubChem Compound
20279
PubChem Substance
46504588
ChemSpider
19105
BindingDB
38920
ChEBI
567361
ChEMBL
CHEMBL1619
Therapeutic Targets Database
DAP000565
PharmGKB
PA449027
HET
CL9
RxList
RxList Drug Page
Drugs.com
Drugs.com Drug Page
Wikipedia
Cladribine
ATC Codes
L01BB04 — Cladribine
AHFS Codes
  • 10:00.00 — Antineoplastic Agents
PDB Entries
2zi9 / 2zia
MSDS
Download (43.7 KB)

Clinical Trials

Clinical Trials
PhaseStatusPurposeConditionsCount
1Active Not RecruitingTreatmentMalignant Lymphomas2
1CompletedTreatmentBrain and Central Nervous System Tumors1
1CompletedTreatmentChronic Myeloproliferative Disorders / Graft Versus Host Disease (GVHD) / Leukemias / Malignant Lymphomas / Multiple Myeloma and Plasma Cell Neoplasm / Myelodysplastic Syndromes / Precancerous/Nonmalignant Condition / Small Intestine Cancer1
1CompletedTreatmentDisseminated Sclerosis1
1CompletedTreatmentLeukemia Acute Myeloid Leukemia (AML)1
1CompletedTreatmentLeukemias2
1RecruitingTreatmentDe Novo Myelodysplastic Syndrome / Mixed Phenotype Acute Leukemia (MPAL) / Previously Treated Myelodysplastic Syndromes / Recurrent Adult Acute Myeloid Leukemia / Recurrent High Risk Myelodysplastic Syndrome / Refractory Acute Myeloid Leukemia / Refractory High Risk Myelodysplastic Syndrome / Untreated Adult Acute Myeloid Leukemia1
1, 2Active Not RecruitingTreatmentMantle Cell Lymphoma (MCL)1
1, 2RecruitingTreatmentAcute Biphenotypic Leukemia (ABL) / De Novo Myelodysplastic Syndrome / Leukemia Acute Myeloid Leukemia (AML) / Myelodysplastic Syndrome / Myeloproliferative Neoplasms1
1, 2RecruitingTreatmentAcute Biphenotypic Leukemia (ABL) / De Novo Myelodysplastic Syndrome / Previously Treated Myelodysplastic Syndromes / Recurrent Adult Acute Myeloid Leukemia / Secondary Acute Myeloid Leukemia / Secondary Myelodysplastic Syndromes / Untreated Adult Acute Myeloid Leukemia1
1, 2RecruitingTreatmentLeukemia Acute Myeloid Leukemia (AML)1
1, 2Unknown StatusTreatmentChronic Lymphocytic Leukaemia (CLL)1
2Active Not RecruitingTreatmentIndolent Lymphoma / Malignant Lymphomas / Mantle Cell Lymphoma (MCL) / SLL1
2Active Not RecruitingTreatmentLangerhans Cell Histiocytosis of Lung1
2CompletedTreatmentAdult Acute Lymphocytic Leukemia T-Cell / Lymphoma, Lymphoblastic1
2CompletedTreatmentDisseminated Sclerosis1
2CompletedTreatmentGraft Versus Host Disease (GVHD) / Leukemias / Myelodysplastic Syndromes1
2CompletedTreatmentHairy Cell Leukemia (HCL)1
2CompletedTreatmentLeukemias5
2CompletedTreatmentLymphoma of Mucosa-Associated Lymphoid Tissue1
2CompletedTreatmentMalignant Lymphomas2
2CompletedTreatmentRecurrent B-Cell Non-Hodgkin Lymphoma / Recurrent Chronic Lymphocytic Leukemia / Recurrent Indolent Adult Non-Hodgkin Lymphoma / Refractory B-Cell Non-Hodgkin Lymphoma1
2CompletedTreatmentSclerosing Cholangitis1
2RecruitingTreatmentAcute Leukemias of Ambiguous Lineage / Leukemia Acute Myeloid Leukemia (AML) / Myeloid Neoplasm1
2RecruitingTreatmentAcute Lymphoblastic Leukaemias (ALL)1
2RecruitingTreatmentHairy Cell Leukemia (HCL)1
2RecruitingTreatmentLeukemia Acute Myeloid Leukemia (AML) / Myelodysplastic Syndrome1
2RecruitingTreatmentLeukemia Acute Myeloid Leukemia (AML) / Relapsed Leukemia1
2RecruitingTreatmentLeukemias3
2RecruitingTreatmentMalignant Lymphomas1
2TerminatedTreatmentChronic Lymphocytic Leukaemia (CLL) / Small Lymphocytic Lymphoma (SLL)1
2Unknown StatusTreatmentAcute Lymphoblastic Leukaemias (ALL) / Burkitts Leukemia/Lymphoma / Chronic Myelogenous Leukemia (CML) / Lymphoma, Lymphoblastic1
2Unknown StatusTreatmentLeukemia, Myelocytic, Acute1
2, 3Active Not RecruitingTreatmentMyeloid Leukemias1
2, 3RecruitingTreatmentAdvanced Systemic Mastocytosis / Systemic Mastocytosis1
2, 3RecruitingTreatmentHairy Cell Leukemia (HCL)1
2, 3RecruitingTreatmentLangerhans Cell Histiocytosis (LCH)1
3CompletedTreatmentDisseminated Sclerosis1
3CompletedTreatmentLeukemia, Myelocytic, Acute1
3CompletedTreatmentLymphocytic Leukemia, Chronic1
3CompletedTreatmentRelapsing Remitting Multiple Sclerosis (RRMS)2
3RecruitingTreatmentLeukemia Acute Myeloid Leukemia (AML)2
4CompletedTreatmentLymphoma, Lymphoblastic1
4Unknown StatusTreatmentAdult Acute Lymphocytic Leukemia1
Not AvailableActive Not RecruitingNot AvailableDisseminated Sclerosis1
Not AvailableRecruitingTreatmentChronic Myelomonocytic Leukemia-2 / High Grade Malignant Neoplasm / Myelodysplastic Syndrome / Myelodysplastic Syndrome With Excess Blasts-2 / Myeloid Neoplasm / Previously Treated Myelodysplastic Syndromes / Recurrent Adult Acute Myeloid Leukemia / Recurrent Childhood Acute Myeloid Leukemia / Refractory Acute Myeloid Leukemia1

Pharmacoeconomics

Manufacturers
  • App pharmaceuticals llc
  • Bedford laboratories div ben venue laboratories inc
  • Ortho biotech products lp
Packagers
Dosage forms
FormRouteStrength
InjectionIntravenous1 mg/mL
SolutionIntravenous1 mg
Prices
Unit descriptionCostUnit
Leustatin 10 mg/10 ml vial102.78USD ml
Cladribine 10 mg/10 ml vial34.2USD ml
DrugBank does not sell nor buy drugs. Pricing information is supplied for informational purposes only.
Patents
Not Available

Properties

State
Solid
Experimental Properties
PropertyValueSource
melting point (°C)215 °CNot Available
logP-0.1Not Available
Predicted Properties
PropertyValueSource
Water Solubility6.35 mg/mLALOGPS
logP-0.12ALOGPS
logP-0.28ChemAxon
logS-1.6ALOGPS
pKa (Strongest Acidic)13.89ChemAxon
pKa (Strongest Basic)1.33ChemAxon
Physiological Charge0ChemAxon
Hydrogen Acceptor Count7ChemAxon
Hydrogen Donor Count3ChemAxon
Polar Surface Area119.31 Å2ChemAxon
Rotatable Bond Count2ChemAxon
Refractivity67.18 m3·mol-1ChemAxon
Polarizability25.93 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+0.9386
Caco-2 permeable-0.7394
P-glycoprotein substrateNon-substrate0.6469
P-glycoprotein inhibitor INon-inhibitor0.9139
P-glycoprotein inhibitor IINon-inhibitor0.8526
Renal organic cation transporterNon-inhibitor0.8722
CYP450 2C9 substrateNon-substrate0.8948
CYP450 2D6 substrateNon-substrate0.8145
CYP450 3A4 substrateNon-substrate0.5
CYP450 1A2 substrateNon-inhibitor0.7226
CYP450 2C9 inhibitorNon-inhibitor0.8803
CYP450 2D6 inhibitorNon-inhibitor0.9007
CYP450 2C19 inhibitorNon-inhibitor0.8856
CYP450 3A4 inhibitorNon-inhibitor0.831
CYP450 inhibitory promiscuityLow CYP Inhibitory Promiscuity0.8761
Ames testNon AMES toxic0.8673
CarcinogenicityNon-carcinogens0.6795
BiodegradationNot ready biodegradable1.0
Rat acute toxicity2.2055 LD50, mol/kg Not applicable
hERG inhibition (predictor I)Weak inhibitor0.9326
hERG inhibition (predictor II)Non-inhibitor0.8344
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
LC-MS/MS Spectrum - LC-ESI-qTof , PositiveLC-MS/MSNot Available
MS/MS Spectrum - , positiveLC-MS/MSsplash10-00di-1910000000-ab013e8ee7a199f7832a
MS/MS Spectrum - , positiveLC-MS/MSsplash10-00e9-2900000000-e03a0a91db8b01dbf975

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 / N-substituted imidazoles / Imidolactams / Tetrahydrofurans / Heteroaromatic compounds / Secondary alcohols / Oxacyclic compounds
show 6 more
Substituents
Purine 2'-deoxyribonucleoside / 6-aminopurine / Imidazopyrimidine / Purine / Aminopyrimidine / 2-halopyrimidine / Halopyrimidine / N-substituted imidazole / Aryl chloride / Aryl halide
show 23 more
Molecular Framework
Aromatic heteropolycyclic compounds
External Descriptors
organochlorine compound, purine 2'-deoxyribonucleoside (CHEBI:567361)

Targets

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. Sampat K, Kantarjian H, Borthakur G: Clofarabine: emerging role in leukemias. Expert Opin Investig Drugs. 2009 Oct;18(10):1559-64. doi: 10.1517/13543780903173222. [PubMed:19715446]
  2. 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]
  3. 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]
  4. Kline JP, Larson RA: Clofarabine in the treatment of acute myeloid leukaemia and acute lymphoblastic leukaemia: a review. Expert Opin Pharmacother. 2005 Dec;6(15):2711-8. [PubMed:16316309]
  5. Takahashi T, Kanazawa J, Akinaga S, Tamaoki T, Okabe M: Antitumor activity of 2-chloro-9-(2-deoxy-2-fluoro-beta-D-arabinofuranosyl) adenine, a novel deoxyadenosine analog, against human colon tumor xenografts by oral administration. Cancer Chemother Pharmacol. 1999;43(3):233-40. [PubMed:9923554]
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. Inhibits Wnt signaling.
Gene Name
RRM2
Uniprot ID
P31350
Uniprot Name
Ribonucleoside-diphosphate reductase subunit M2
Molecular Weight
44877.25 Da
References
  1. Sampat K, Kantarjian H, Borthakur G: Clofarabine: emerging role in leukemias. Expert Opin Investig Drugs. 2009 Oct;18(10):1559-64. doi: 10.1517/13543780903173222. [PubMed:19715446]
  2. 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]
  3. 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]
  4. Kline JP, Larson RA: Clofarabine in the treatment of acute myeloid leukaemia and acute lymphoblastic leukaemia: a review. Expert Opin Pharmacother. 2005 Dec;6(15):2711-8. [PubMed:16316309]
  5. Takahashi T, Kanazawa J, Akinaga S, Tamaoki T, Okabe M: Antitumor activity of 2-chloro-9-(2-deoxy-2-fluoro-beta-D-arabinofuranosyl) adenine, a novel deoxyadenosine analog, against human colon tumor xenografts by oral administration. Cancer Chemother Pharmacol. 1999;43(3):233-40. [PubMed:9923554]
Kind
Protein
Organism
Human
Pharmacological action
Yes
Actions
Inhibitor
General Function
Ribonucleoside-diphosphate reductase activity, thioredoxin disulfide as acceptor
Specific Function
Plays a pivotal role in cell survival by repairing damaged DNA in a p53/TP53-dependent manner. Supplies deoxyribonucleotides for DNA repair in cells arrested at G1 or G2. Contains an iron-tyrosyl f...
Gene Name
RRM2B
Uniprot ID
Q7LG56
Uniprot Name
Ribonucleoside-diphosphate reductase subunit M2 B
Molecular Weight
40736.11 Da
References
  1. Sampat K, Kantarjian H, Borthakur G: Clofarabine: emerging role in leukemias. Expert Opin Investig Drugs. 2009 Oct;18(10):1559-64. doi: 10.1517/13543780903173222. [PubMed:19715446]
  2. 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]
  3. 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]
  4. Kline JP, Larson RA: Clofarabine in the treatment of acute myeloid leukaemia and acute lymphoblastic leukaemia: a review. Expert Opin Pharmacother. 2005 Dec;6(15):2711-8. [PubMed:16316309]
  5. Takahashi T, Kanazawa J, Akinaga S, Tamaoki T, Okabe M: Antitumor activity of 2-chloro-9-(2-deoxy-2-fluoro-beta-D-arabinofuranosyl) adenine, a novel deoxyadenosine analog, against human colon tumor xenografts by oral administration. Cancer Chemother Pharmacol. 1999;43(3):233-40. [PubMed:9923554]
4. 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. 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. Sampat K, Kantarjian H, Borthakur G: Clofarabine: emerging role in leukemias. Expert Opin Investig Drugs. 2009 Oct;18(10):1559-64. doi: 10.1517/13543780903173222. [PubMed:19715446]
  4. 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]
  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]
  6. Kline JP, Larson RA: Clofarabine in the treatment of acute myeloid leukaemia and acute lymphoblastic leukaemia: a review. Expert Opin Pharmacother. 2005 Dec;6(15):2711-8. [PubMed:16316309]
  7. Hartman WR, Hentosh P: The antileukemia drug 2-chloro-2'-deoxyadenosine: an intrinsic transcriptional antagonist. Mol Pharmacol. 2004 Jan;65(1):227-34. [PubMed:14722255]
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. 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]
  2. Kline JP, Larson RA: Clofarabine in the treatment of acute myeloid leukaemia and acute lymphoblastic leukaemia: a review. Expert Opin Pharmacother. 2005 Dec;6(15):2711-8. [PubMed:16316309]
  3. Takahashi T, Kanazawa J, Akinaga S, Tamaoki T, Okabe M: Antitumor activity of 2-chloro-9-(2-deoxy-2-fluoro-beta-D-arabinofuranosyl) adenine, a novel deoxyadenosine analog, against human colon tumor xenografts by oral administration. Cancer Chemother Pharmacol. 1999;43(3):233-40. [PubMed:9923554]
  4. Hartman WR, Hentosh P: The antileukemia drug 2-chloro-2'-deoxyadenosine: an intrinsic transcriptional antagonist. Mol Pharmacol. 2004 Jan;65(1):227-34. [PubMed:14722255]
Kind
Protein
Organism
Human
Pharmacological action
Yes
Actions
Inhibitor
General Function
Zinc ion binding
Specific Function
Participates in DNA repair and in chromosomal DNA replication.
Gene Name
POLE
Uniprot ID
Q07864
Uniprot Name
DNA polymerase epsilon catalytic subunit A
Molecular Weight
261515.525 Da
References
  1. 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
Dna-directed dna polymerase activity
Specific Function
Participates in DNA repair and in chromosomal DNA replication.
Gene Name
POLE2
Uniprot ID
P56282
Uniprot Name
DNA polymerase epsilon subunit 2
Molecular Weight
59536.64 Da
References
  1. 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
Dna-directed dna polymerase activity
Specific Function
Forms a complex with DNA polymerase epsilon subunit CHRAC1 and binds naked DNA, which is then incorporated into chromatin, aided by the nucleosome-remodeling activity of ISWI/SNF2H and ACF1.
Gene Name
POLE3
Uniprot ID
Q9NRF9
Uniprot Name
DNA polymerase epsilon subunit 3
Molecular Weight
16859.4 Da
References
  1. 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
Dna-directed dna polymerase activity
Specific Function
May play a role in allowing polymerase epsilon to carry out its replication and/or repair function.
Gene Name
POLE4
Uniprot ID
Q9NR33
Uniprot Name
DNA polymerase epsilon subunit 4
Molecular Weight
12208.63 Da
References
  1. 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
Inducer
General Function
Purine-nucleoside phosphorylase activity
Specific Function
The purine nucleoside phosphorylases catalyze the phosphorolytic breakdown of the N-glycosidic bond in the beta-(deoxy)ribonucleoside molecules, with the formation of the corresponding free purine ...
Gene Name
PNP
Uniprot ID
P00491
Uniprot Name
Purine nucleoside phosphorylase
Molecular Weight
32117.69 Da
References
  1. Bzowska A, Kazimierczuk Z: 2-Chloro-2'-deoxyadenosine (cladribine) and its analogues are good substrates and potent selective inhibitors of Escherichia coli purine-nucleoside phosphorylase. Eur J Biochem. 1995 Nov 1;233(3):886-90. [PubMed:8521855]
  2. Dumontet C, Fabianowska-Majewska K, Mantincic D, Callet Bauchu E, Tigaud I, Gandhi V, Lepoivre M, Peters GJ, Rolland MO, Wyczechowska D, Fang X, Gazzo S, Voorn DA, Vanier-Viornery A, MacKey J: Common resistance mechanisms to deoxynucleoside analogues in variants of the human erythroleukaemic line K562. Br J Haematol. 1999 Jul;106(1):78-85. [PubMed:10444166]
  3. Dumontet C, Bauchu EC, Fabianowska K, Lepoivre M, Wyczechowska D, Bodin F, Rolland MO: Common resistance mechanisms to nucleoside analogues in variants of the human erythroleukemic line K562. Adv Exp Med Biol. 1999;457:571-7. [PubMed:10500836]
  4. Takimoto T, Kubota M, Tsuruta S, Kitoh T, Tanizawa A, Akiyama Y, Kiriyama Y, Mikawa H: Changes in sensitivity to anticancer drugs during TPA-induced cellular differentiation in a human T-lymphoblastoid cell line (MOLT-4). Leukemia. 1988 Jul;2(7):443-6. [PubMed:3260648]
  5. Carson DA, Wasson DB, Lakow E, Kamatani N: Possible metabolic basis for the different immunodeficient states associated with genetic deficiencies of adenosine deaminase and purine nucleoside phosphorylase. Proc Natl Acad Sci U S A. 1982 Jun;79(12):3848-52. [PubMed:6808516]

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. Warnke C, Wiendl H, Hartung HP, Stuve O, Kieseier BC: Identification of targets and new developments in the treatment of multiple sclerosis--focus on cladribine. Drug Des Devel Ther. 2010 Jul 21;4:117-26. [PubMed:20689698]
  2. Sigal DS, Miller HJ, Schram ED, Saven A: Beyond hairy cell: the activity of cladribine in other hematologic malignancies. Blood. 2010 Oct 21;116(16):2884-96. doi: 10.1182/blood-2010-02-246140. Epub 2010 Jul 15. [PubMed:20634380]
  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]
  4. Sampat K, Kantarjian H, Borthakur G: Clofarabine: emerging role in leukemias. Expert Opin Investig Drugs. 2009 Oct;18(10):1559-64. doi: 10.1517/13543780903173222. [PubMed:19715446]
  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]
  6. 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]

Transporters

Kind
Protein
Organism
Human
Pharmacological action
Unknown
Actions
Substrate
General Function
Quaternary ammonium group transmembrane transporter activity
Specific Function
Mediates tubular uptake of organic compounds from circulation. Mediates the influx of agmatine, dopamine, noradrenaline (norepinephrine), serotonin, choline, famotidine, ranitidine, histamin, creat...
Gene Name
SLC22A2
Uniprot ID
O15244
Uniprot Name
Solute carrier family 22 member 2
Molecular Weight
62579.99 Da
References
  1. Chen R, Nelson JA: Role of organic cation transporters in the renal secretion of nucleosides. Biochem Pharmacol. 2000 Jul 15;60(2):215-9. [PubMed:10825466]
Kind
Protein
Organism
Human
Pharmacological action
Unknown
Actions
Substrate
General Function
Secondary active organic cation transmembrane transporter activity
Specific Function
Translocates a broad array of organic cations with various structures and molecular weights including the model compounds 1-methyl-4-phenylpyridinium (MPP), tetraethylammonium (TEA), N-1-methylnico...
Gene Name
SLC22A1
Uniprot ID
O15245
Uniprot Name
Solute carrier family 22 member 1
Molecular Weight
61153.345 Da
References
  1. Chen R, Nelson JA: Role of organic cation transporters in the renal secretion of nucleosides. Biochem Pharmacol. 2000 Jul 15;60(2):215-9. [PubMed:10825466]
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]
Kind
Protein
Organism
Human
Pharmacological action
Unknown
General Function
Pyrimidine- and adenine-specific:sodium symporter activity
Specific Function
Sodium-dependent, pyrimidine- and purine-selective. Involved in the homeostasis of endogenous nucleosides. Exhibits the transport characteristics of the nucleoside transport system cib or N3 subtyp...
Gene Name
SLC28A3
Uniprot ID
Q9HAS3
Uniprot Name
Solute carrier family 28 member 3
Molecular Weight
76929.61 Da
References
  1. Badagnani I, Chan W, Castro RA, Brett CM, Huang CC, Stryke D, Kawamoto M, Johns SJ, Ferrin TE, Carlson EJ, Burchard EG, Giacomini KM: Functional analysis of genetic variants in the human concentrative nucleoside transporter 3 (CNT3; SLC28A3). Pharmacogenomics J. 2005;5(3):157-65. [PubMed:15738947]

Drug created on June 13, 2005 07:24 / Updated on November 19, 2017 20:33