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Identification
NameCladribine
Accession NumberDB00242  (APRD00260)
TypeSmall Molecule
GroupsApproved, Investigational
Description

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

Structure
Thumb
Synonyms
SynonymLanguageCode
(2R,3S,5R)-5-(6-amino-2-Chloropurin-9-yl)-2-(hydroxymethyl)oxolan-3-olNot AvailableNot Available
2-CdANot AvailableNot Available
2-Chloro-2'-deoxy-beta-adenosineNot AvailableNot Available
2-Chloro-2'-deoxyadenosineNot AvailableNot Available
2-chloro-6-amino-9-(2-Deoxy-beta-D-erythro-pentofuranosyl)purineNot AvailableNot Available
2-chloro-DeoxyadenosineNot AvailableNot Available
2-ChlorodeoxyadenosineNot AvailableNot Available
2ClAdoNot AvailableNot Available
CladribinaNot AvailableNot Available
CladribineNot AvailableNot Available
CladribinumNot AvailableNot Available
CldAdoNot AvailableNot Available
SaltsNot Available
Brand names
NameCompany
LeustatinNot Available
LitakNot Available
MovectroNot Available
MylinaxNot Available
Brand mixturesNot Available
Categories
CAS number4291-63-8
WeightAverage: 285.687
Monoisotopic: 285.062866982
Chemical FormulaC10H12ClN5O3
InChI KeyPTOAARAWEBMLNO-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([C@H]3C[C@H](O)[C@@H](CO)O3)C2=NC(Cl)=N1
Mass SpecNot Available
Taxonomy
KingdomOrganic Compounds
SuperclassOrganooxygen Compounds
ClassCarbohydrates and Carbohydrate Conjugates
SubclassGlycosyl Compounds
Direct parentPurine 2'-deoxyribonucleosides and Analogues
Alternative parentsPentoses; Purines and Purine Derivatives; Aminopyrimidines and Derivatives; Halopyrimidines; Primary Aromatic Amines; Aryl Chlorides; N-substituted Imidazoles; Oxolanes; Tetrahydrofurans; Secondary Alcohols; Ethers; Polyamines; Primary Alcohols; Organochlorides
Substituentspentose monosaccharide; purine; imidazopyrimidine; aminopyrimidine; halopyrimidine; n-substituted imidazole; aryl halide; primary aromatic amine; monosaccharide; aryl chloride; pyrimidine; tetrahydrofuran; imidazole; oxolane; azole; secondary alcohol; ether; polyamine; primary alcohol; organohalogen; primary amine; organochloride; alcohol; organonitrogen compound; amine
Classification descriptionThis compound belongs to the purine 2'-deoxyribonucleosides and analogues. These are compounds consisting of a purine linked to a ribose which lacks an hydroxyl group at position 2.
Pharmacology
IndicationFor 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.
PharmacodynamicsCladribine 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 actionCladribine 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.
AbsorptionOral bioavailability is 34 to 48%.
Volume of distribution
  • 4.5 ± 2.8 L/kg [patients with hematologic malignancies]
  • 9 L/kg
Protein binding20%
Metabolism

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

SubstrateEnzymesProduct
Cladribine
Not Available
2-chloro-2'-deoxyadenosine-5'-triphosphateDetails
Route of eliminationNot Available
Half life5.4 hours
Clearance
  • 978 +/- 422 mL/h/kg
ToxicitySymptoms 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
PathwaysNot Available
SNP Mediated EffectsNot Available
SNP Mediated Adverse Drug ReactionsNot Available
ADMET
Predicted ADMET features
Property Value Probability
Human Intestinal Absorption + 1.0
Blood Brain Barrier + 0.9386
Caco-2 permeable - 0.7394
P-glycoprotein substrate Non-substrate 0.6469
P-glycoprotein inhibitor I Non-inhibitor 0.9139
P-glycoprotein inhibitor II Non-inhibitor 0.8526
Renal organic cation transporter Non-inhibitor 0.8722
CYP450 2C9 substrate Non-substrate 0.8948
CYP450 2D6 substrate Non-substrate 0.8145
CYP450 3A4 substrate Non-substrate 0.5
CYP450 1A2 substrate Non-inhibitor 0.7226
CYP450 2C9 substrate Non-inhibitor 0.8803
CYP450 2D6 substrate Non-inhibitor 0.9007
CYP450 2C19 substrate Non-inhibitor 0.8856
CYP450 3A4 substrate Non-inhibitor 0.831
CYP450 inhibitory promiscuity Low CYP Inhibitory Promiscuity 0.8761
Ames test Non AMES toxic 0.8673
Carcinogenicity Non-carcinogens 0.6795
Biodegradation Not ready biodegradable 1.0
Rat acute toxicity 2.2055 LD50, mol/kg Not applicable
hERG inhibition (predictor I) Weak inhibitor 0.9326
hERG inhibition (predictor II) Non-inhibitor 0.8344
Pharmacoeconomics
Manufacturers
  • App pharmaceuticals llc
  • Bedford laboratories div ben venue laboratories inc
  • Ortho biotech products lp
Packagers
Dosage forms
FormRouteStrength
SolutionIntravenous
Prices
Unit descriptionCostUnit
Leustatin 10 mg/10 ml vial102.78USDml
Cladribine 10 mg/10 ml vial34.2USDml
DrugBank does not sell nor buy drugs. Pricing information is supplied for informational purposes only.
PatentsNot Available
Properties
Statesolid
Experimental Properties
PropertyValueSource
melting point215 °CNot Available
logP-0.1Not Available
Predicted Properties
PropertyValueSource
Water Solubility6.35ALOGPS
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
Spectra
SpectraNot Available
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 Reference
  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
  2. Sigal DS, Miller HJ, Schram ED, Saven A: Beyond hairy cell: the activity of cladribine in other hematologic malignancies. Blood. 2010 Jul 15. Pubmed
  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
  4. Sampat K, Kantarjian H, Borthakur G: Clofarabine: emerging role in leukemias. Expert Opin Investig Drugs. 2009 Oct;18(10):1559-64. Pubmed
  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
  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. Epub 2009 Jul 1. Pubmed
  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. Pubmed
External Links
ResourceLink
KEGG DrugD01370
PubChem Compound20279
PubChem Substance46504588
ChemSpider19105
ChEBI567361
ChEMBLCHEMBL1619
Therapeutic Targets DatabaseDAP000565
PharmGKBPA449027
Drug Product Database2022117
RxListhttp://www.rxlist.com/cgi/generic3/cladribine.htm
Drugs.comhttp://www.drugs.com/cdi/cladribine.html
WikipediaCladribine
ATC CodesL01BB04
AHFS Codes
  • 10:00.00
PDB Entries
FDA labelNot Available
MSDSshow(43.7 KB)
Interactions
Drug Interactions
Drug
LeflunomideImmunosuppressants such as cladribine may enhance the adverse/toxic effect of leflunomide. Specifically, the risk for hematologic toxicity such as pancytopenia, agranulocytosis, and/or thrombocytopenia may be increased. Consider eliminating the use of a leflunomide loading dose in patients who are receiving other immunosuppressants in order to reduce the risk for serious adverse events such as hematologic toxicity. Also, patients receiving both leflunomide and another immunosuppressive medication should be monitored for bone marrow suppression at least monthly throughout the duration of concurrent therapy.
NatalizumabImmunosuppressants such as cladribine may enhance the adverse/toxic effect of natalizumab. Specifically, the risk of concurrent infection may be increased. Patients receiving natalizumab should not use concurrent immunosuppressants, and patients receiving chronic corticosteroids prior to natalizumab should be tapered off of steroids prior to starting natalizumab.
PimecrolimusPimecrolimus may enhance the adverse/toxic effect of immunosuppressants such as cladribine. Avoid use of pimecrolimus cream in patients receiving immunosuppressants.
RoflumilastRoflumilast may enhance the immunosuppressive effect of immunosuppressants such as cladribine. The Canadian roflumilast product monograph recommends avoiding concurrent use of roflumilast with any immunosuppressant medications due to the antiinflammatory/immune altering effects of roflumilast and the lack of relevant clinical experience with such use. Of note, this recommendation to avoid concurrent use does not apply to either inhaled corticosteroids (which have much more limited systemic immune-suppressing actions) or short-term systemic corticosteroid use. U.S. prescribing information does not contain this warning; but it appears prudent to avoid this combination when possible.
TacrolimusTacrolimus (Topical) may enhance the adverse/toxic effect of immunosuppressants such as tacrolimus. Avoid use of tacrolimus ointment in patients receiving immunosuppressants.
TrastuzumabTrastuzumab may increase the risk of neutropenia and anemia. Monitor closely for signs and symptoms of adverse events.
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.

Targets

1. Ribonucleoside-diphosphate reductase large subunit

Kind: protein

Organism: Human

Pharmacological action: yes

Actions: inhibitor

Components

Name UniProt ID Details
Ribonucleoside-diphosphate reductase large subunit P23921 Details

References:

  1. Sampat K, Kantarjian H, Borthakur G: Clofarabine: emerging role in leukemias. Expert Opin Investig Drugs. 2009 Oct;18(10):1559-64. Pubmed
  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
  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. Epub 2009 Jul 1. Pubmed
  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
  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

2. Ribonucleoside-diphosphate reductase subunit M2

Kind: protein

Organism: Human

Pharmacological action: yes

Actions: inhibitor

Components

Name UniProt ID Details
Ribonucleoside-diphosphate reductase subunit M2 P31350 Details

References:

  1. Sampat K, Kantarjian H, Borthakur G: Clofarabine: emerging role in leukemias. Expert Opin Investig Drugs. 2009 Oct;18(10):1559-64. Pubmed
  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
  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. Epub 2009 Jul 1. Pubmed
  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
  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

3. Ribonucleoside-diphosphate reductase subunit M2 B

Kind: protein

Organism: Human

Pharmacological action: yes

Actions: inhibitor

Components

Name UniProt ID Details
Ribonucleoside-diphosphate reductase subunit M2 B Q7LG56 Details

References:

  1. Sampat K, Kantarjian H, Borthakur G: Clofarabine: emerging role in leukemias. Expert Opin Investig Drugs. 2009 Oct;18(10):1559-64. Pubmed
  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
  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. Epub 2009 Jul 1. Pubmed
  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
  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

4. DNA

Kind: nucleotide

Organism: Human

Pharmacological action: yes

Actions: other/unknown

Components

Name UniProt ID Details

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
  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
  3. Sampat K, Kantarjian H, Borthakur G: Clofarabine: emerging role in leukemias. Expert Opin Investig Drugs. 2009 Oct;18(10):1559-64. Pubmed
  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
  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. Epub 2009 Jul 1. Pubmed
  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
  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

5. DNA polymerase alpha catalytic subunit

Kind: protein

Organism: Human

Pharmacological action: yes

Actions: inhibitor

Components

Name UniProt ID Details
DNA polymerase alpha catalytic subunit P09884 Details

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. Epub 2009 Jul 1. Pubmed
  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
  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
  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

6. DNA polymerase epsilon catalytic subunit A

Kind: protein

Organism: Human

Pharmacological action: yes

Actions: inhibitor

Components

Name UniProt ID Details
DNA polymerase epsilon catalytic subunit A Q07864 Details

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. Epub 2009 Jul 1. Pubmed

7. DNA polymerase epsilon subunit 2

Kind: protein

Organism: Human

Pharmacological action: yes

Actions: inhibitor

Components

Name UniProt ID Details
DNA polymerase epsilon subunit 2 P56282 Details

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. Epub 2009 Jul 1. Pubmed

8. DNA polymerase epsilon subunit 3

Kind: protein

Organism: Human

Pharmacological action: yes

Actions: inhibitor

Components

Name UniProt ID Details
DNA polymerase epsilon subunit 3 Q9NRF9 Details

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. Epub 2009 Jul 1. Pubmed

9. DNA polymerase epsilon subunit 4

Kind: protein

Organism: Human

Pharmacological action: yes

Actions: inhibitor

Components

Name UniProt ID Details
DNA polymerase epsilon subunit 4 Q9NR33 Details

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. Epub 2009 Jul 1. Pubmed

10. Purine nucleoside phosphorylase

Kind: protein

Organism: Human

Pharmacological action: yes

Actions: inducer

Components

Name UniProt ID Details
Purine nucleoside phosphorylase P00491 Details

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
  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
  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
  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
  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

Enzymes

1. Deoxycytidine kinase

Kind: protein

Organism: Human

Pharmacological action: unknown

Actions: substrate

Components

Name UniProt ID Details
Deoxycytidine kinase P27707 Details

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
  2. Sigal DS, Miller HJ, Schram ED, Saven A: Beyond hairy cell: the activity of cladribine in other hematologic malignancies. Blood. 2010 Jul 15. Pubmed
  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
  4. Sampat K, Kantarjian H, Borthakur G: Clofarabine: emerging role in leukemias. Expert Opin Investig Drugs. 2009 Oct;18(10):1559-64. Pubmed
  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. Epub 2009 Jul 1. Pubmed
  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. Pubmed

Transporters

1. Solute carrier family 22 member 2

Kind: protein

Organism: Human

Pharmacological action: unknown

Actions: substrate

Components

Name UniProt ID Details
Solute carrier family 22 member 2 O15244 Details

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

2. Solute carrier family 22 member 1

Kind: protein

Organism: Human

Pharmacological action: unknown

Actions: substrate

Components

Name UniProt ID Details
Solute carrier family 22 member 1 O15245 Details

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

3. ATP-binding cassette sub-family G member 2

Kind: protein

Organism: Human

Pharmacological action: unknown

Actions: substrate

Components

Name UniProt ID Details
ATP-binding cassette sub-family G member 2 Q9UNQ0 Details

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. Epub 2008 Sep 2. Pubmed

4. Solute carrier family 28 member 3

Kind: protein

Organism: Human

Pharmacological action: unknown

Components

Name UniProt ID Details
Solute carrier family 28 member 3 Q9HAS3 Details

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

Comments
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Drug created on June 13, 2005 07:24 / Updated on September 16, 2013 17:08