Cladribine

This drug entry is a stub and has not been fully annotated. It is scheduled to be annotated soon.

Identification

Summary

Cladribine is a purine antimetabolite used for the management of relapsing forms of Multiple Sclerosis (MS), used in patients who have not responded to or who were unable to tolerate alternative MS drugs.

Brand Names
Litak, Mavenclad
Generic Name
Cladribine
DrugBank Accession Number
DB00242
Background

An antineoplastic agent used in the treatment of lymphoproliferative diseases including hairy-cell leukemia. Cladribine is also used to treat relapsing forms of multiple sclerosis.

Type
Small Molecule
Groups
Approved, Investigational
Structure
Weight
Average: 285.687
Monoisotopic: 285.062866982
Chemical Formula
C10H12ClN5O3
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-β-D-erythro-pentofuranosyl)purine
  • 2-chloro-deoxyadenosine
  • 2-Chlorodeoxyadenosine
  • 2ClAdo
  • Cladribina
  • Cladribine
  • Cladribinum
  • CldAdo
External IDs
  • RWJ 26251
  • RWJ-26251
  • RWJ26251

Pharmacology

Indication

Intravenous cladribine is indicated for the treatment of active Hairy Cell Leukemia as defined by clinically significant anemia, neutropenia, thrombocytopenia or disease-related symptoms.9

Oral cladribine is indicated for the treatment of relapsing forms of multiple sclerosis (MS), including relapsing-remitting disease and active secondary progressive disease, in adults. Because of its safety profile, the use of cladribine is generally recommended for patients who have had an inadequate response to, or are unable to tolerate, an alternate drug indicated for the treatment of MS.8

Reduce drug development failure rates
Build, train, & validate machine-learning models
with evidence-based and structured datasets.
See how
Build, train, & validate predictive machine-learning models with structured datasets.
See how
Associated Conditions
Indication TypeIndicationCombined Product DetailsApproval LevelAge GroupPatient CharacteristicsDose Form
Treatment ofChronic lymphocytic leukemia••• •••••
Treatment ofCutaneous t-cell lymphoma••• •••••
Treatment ofHairy cell leukemia••••••••••••
Treatment ofNon-hodgkin's lymphoma••• •••••
Treatment ofRelapsing multiple sclerosis (rms)•••••••••••••••••
Contraindications & Blackbox Warnings
Prevent Adverse Drug Events Today
Tap into our Clinical API for life-saving information on contraindications & blackbox warnings, population restrictions, harmful risks, & more.
Learn more
Avoid life-threatening adverse drug events with our Clinical API
Learn more
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. Cladribine also has therapeutic effects in patients with multiple sclerosis; although the mechanism of action for this therapeutic effect is not fully elucidated, it is thought to involve cytotoxic effects on B and T lymphocytes by impairing DNA synthesis which in turn results in depletion of lymphocytes.

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

Hover over products below to view reaction partners

Route of elimination

Not Available

Half-life

5.4 hours

Clearance
  • 978 +/- 422 mL/h/kg
Adverse Effects
Improve decision support & research outcomes
With structured adverse effects data, including: blackbox warnings, adverse reactions, warning & precautions, & incidence rates. View sample adverse effects data in our new Data Library!
See the data
Improve decision support & research outcomes with our structured adverse effects data.
See a data sample
Toxicity

Intraperitoneal LD50 is 150 mg/kg in mice.10

High doses of cladribine have been associated with irreversible neurologic toxicity (paraparesis/quadriparesis), acute nephrotoxicity, and severe bone marrow suppression resulting in neutropenia, anemia, and thrombocytopenia.9 Lymphopenia may also occur, which is known to be dose-dependent.8 There is no known antidote to cladribine overdosage; thus, treatment of overdosage consists of drug discontinuation, careful observation, and appropriate supportive measures.9 Although it is not known whether cladribine can be removed from the circulation by dialysis or hemofiltration, because of its rapid and extensive intracellular and tissue distribution, hemodialysis is unlikely to eliminate cladribine to a significant extent.8

Pathways
Not Available
Pharmacogenomic Effects/ADRs
Not Available

Interactions

Drug Interactions
This information should not be interpreted without the help of a healthcare provider. If you believe you are experiencing an interaction, contact a healthcare provider immediately. The absence of an interaction does not necessarily mean no interactions exist.
DrugInteraction
AbataceptThe risk or severity of adverse effects can be increased when Cladribine is combined with Abatacept.
AbciximabThe risk or severity of bleeding can be increased when Abciximab is combined with Cladribine.
AcenocoumarolThe risk or severity of bleeding can be increased when Acenocoumarol is combined with Cladribine.
AcetyldigitoxinAcetyldigitoxin may decrease the cardiotoxic activities of Cladribine.
Acetylsalicylic acidThe risk or severity of bleeding can be increased when Acetylsalicylic acid is combined with Cladribine.
Food Interactions
  • Take with or without food. When taken with oral tablets of cladribine, food decreases Cmax and prolongs Tmax, but not to a clinically significant extent.

Products

Drug product information from 10+ global regions
Our datasets provide approved product information including:
dosage, form, labeller, route of administration, and marketing period.
Access now
Access drug product information from over 10 global regions.
Access now
International/Other Brands
Litak / Movectro / Mylinax
Brand Name Prescription Products
NameDosageStrengthRouteLabellerMarketing StartMarketing EndRegionImage
Cladribine InjectionSolution1 mg / mLIntravenousFresenius Kabi2009-06-30Not applicableCanada flag
Cladribine InjectionSolution1 mg / mLIntravenousGeneric Medical Partners Inc2020-08-19Not applicableCanada flag
LeustatinInjection, solution1 mg/1mLIntravenousJanssen Products, L.P.1993-03-012013-09-30US flag
Leustatin 1mg/mlSolution1 mg / mLIntravenousJanssen Pharmaceuticals1993-12-312011-12-19Canada flag
LitakInjection, solution2 mg/mlSubcutaneousLipomed2020-12-16Not applicableEU flag
Generic Prescription Products
NameDosageStrengthRouteLabellerMarketing StartMarketing EndRegionImage
CladribineInjection, solution1 mg/1mLIntravenousHisun Pharmaceuticals Usa, Inc.2020-05-18Not applicableUS flag
CladribineInjection1 mg/1mLIntravenousMylan Institutional LLC2011-07-102022-12-31US flag
CladribineInjection1 mg/1mLIntravenousBedford Pharmaceuticals2000-02-282012-12-31US flag
CladribineInjection1 mg/1mLIntravenousPfizer Laboratories Div Pfizer Inc.2011-10-072017-12-31US flag
CladribineInjection1 mg/1mLIntravenousFresenius Kabi USA, LLC2004-12-01Not applicableUS flag

Categories

ATC Codes
L04AA40 — CladribineL01BB04 — Cladribine
Drug Categories
Chemical TaxonomyProvided by Classyfire
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
2-halopyrimidine / 6-aminopurine / Alcohol / Amine / Aminopyrimidine / Aromatic heteropolycyclic compound / Aryl chloride / Aryl halide / Azacycle / Azole
show 23 more
Molecular Framework
Aromatic heteropolycyclic compounds
External Descriptors
organochlorine compound, purine 2'-deoxyribonucleoside (CHEBI:567361)
Affected organisms
  • Humans and other mammals

Chemical Identifiers

UNII
47M74X9YT5
CAS number
4291-63-8
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([C@H]3C[C@H](O)[C@@H](CO)O3)C2=NC(Cl)=N1

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. [Article]
  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. [Article]
  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. [Article]
  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. [Article]
  5. Kantarjian HM, Jeha S, Gandhi V, Wess M, Faderl S: Clofarabine: past, present, and future. Leuk Lymphoma. 2007 Oct;48(10):1922-30. [Article]
  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. [Article]
  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. [Article]
  8. FDA Approved Drug Products: MAVENCLAD (cladribine) tablets, for oral use (December 2023) [Link]
  9. DailyMed Label: Cladribine Intravenous Injection [Link]
  10. Cayman Chemical: Cladribine MSDS [Link]
Human Metabolome Database
HMDB0014387
KEGG Drug
D01370
PubChem Compound
20279
PubChem Substance
46504588
ChemSpider
19105
BindingDB
38920
RxNav
44157
ChEBI
567361
ChEMBL
CHEMBL1619
ZINC
ZINC000003798064
Therapeutic Targets Database
DAP000565
PharmGKB
PA449027
PDBe Ligand
CL9
RxList
RxList Drug Page
Drugs.com
Drugs.com Drug Page
Wikipedia
Cladribine
PDB Entries
2zi9 / 2zia
MSDS
Download (43.7 KB)

Clinical Trials

Clinical Trials
PhaseStatusPurposeConditionsCount
4Active Not RecruitingBasic ScienceMultiple Sclerosis / Relapsing Remitting Multiple Sclerosis (RRMS)1
4Active Not RecruitingTreatmentMultiple Sclerosis1
4Active Not RecruitingTreatmentRelapsing Remitting Multiple Sclerosis (RRMS)2
4CompletedOtherMultiple Sclerosis2
4CompletedTreatmentLeukemia, Lymphocytic, Acute, Adult1

Pharmacoeconomics

Manufacturers
  • App pharmaceuticals llc
  • Bedford laboratories div ben venue laboratories inc
  • Ortho biotech products lp
Packagers
  • APP Pharmaceuticals
  • Bedford Labs
  • Ben Venue Laboratories Inc.
  • Centocor Ortho Biotech Inc.
Dosage Forms
FormRouteStrength
InjectionIntravenous1 mg/1mL
InjectionIntravenous10 MG/10ML
Injection, solutionIntravenous1 mg/1mL
SolutionIntravenous1 mg / mL
SolutionIntravenous1 mg
Injection, solutionParenteral; Subcutaneous2 MG/ML
Injection, solutionSubcutaneous2 mg/ml
SolutionIntravenous; Subcutaneous2 mg
SolutionIntravenous; Subcutaneous200000 mg
TabletOral10 mg/1
TabletOral10.000 mg
TabletOral10 mg
Injection, solution2 mg/ml
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
Patent NumberPediatric ExtensionApprovedExpires (estimated)Region
US7888328No2011-02-152024-04-11US flag
US8785415No2014-07-222024-04-11US flag
US7713947No2010-05-112026-10-16US flag
US8377903No2013-02-192026-05-31US flag
US10849919No2020-12-012038-11-23US flag

Properties

State
Solid
Experimental Properties
Not 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)2.22Chemaxon
Physiological Charge0Chemaxon
Hydrogen Acceptor Count7Chemaxon
Hydrogen Donor Count3Chemaxon
Polar Surface Area119.31 Å2Chemaxon
Rotatable Bond Count2Chemaxon
Refractivity67.18 m3·mol-1Chemaxon
Polarizability26.85 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-MSsplash10-0006-9140000000-2241274903b14d6388f8
LC-MS/MS Spectrum - LC-ESI-qTof , PositiveLC-MS/MSsplash10-00di-1910000000-ab013e8ee7a199f7832a
LC-MS/MS Spectrum - LC-ESI-qTof , PositiveLC-MS/MSsplash10-00e9-2900000000-e03a0a91db8b01dbf975
MS/MS Spectrum - , positiveLC-MS/MSsplash10-00di-1910000000-ab013e8ee7a199f7832a
MS/MS Spectrum - , positiveLC-MS/MSsplash10-00e9-2900000000-e03a0a91db8b01dbf975
Predicted MS/MS Spectrum - 10V, Positive (Annotated)Predicted LC-MS/MSsplash10-000i-0090000000-5dcb49a75653dff90a36
Predicted MS/MS Spectrum - 10V, Negative (Annotated)Predicted LC-MS/MSsplash10-001i-0190000000-cb5800439f2ec50d81d6
Predicted MS/MS Spectrum - 20V, Positive (Annotated)Predicted LC-MS/MSsplash10-00di-0910000000-979a7b3c656c93339796
Predicted MS/MS Spectrum - 20V, Negative (Annotated)Predicted LC-MS/MSsplash10-0159-0980000000-18bedd39052ac89a7db7
Predicted MS/MS Spectrum - 40V, Positive (Annotated)Predicted LC-MS/MSsplash10-00di-0900000000-4d09b6b8448defb6a5d9
Predicted MS/MS Spectrum - 40V, Negative (Annotated)Predicted LC-MS/MSsplash10-001i-2900000000-a162cc34a1e925609c68
Predicted 1H NMR Spectrum1D NMRNot Applicable
Predicted 13C NMR Spectrum1D NMRNot Applicable
Chromatographic Properties
Collision Cross Sections (CCS)
AdductCCS Value (Å2)Source typeSource
[M-H]-166.1812149
predicted
DarkChem Lite v0.1.0
[M-H]-161.9079659
predicted
DarkChem Lite v0.1.0
[M-H]-160.90352
predicted
DeepCCS 1.0 (2019)
[M+H]+166.7559149
predicted
DarkChem Lite v0.1.0
[M+H]+160.7847969
predicted
DarkChem Lite v0.1.0
[M+H]+163.26152
predicted
DeepCCS 1.0 (2019)
[M+Na]+166.1916149
predicted
DarkChem Lite v0.1.0
[M+Na]+166.41
predicted
DarkChem Lite v0.1.0
[M+Na]+169.98991
predicted
DeepCCS 1.0 (2019)

Targets

Build, predict & validate machine-learning models
Use our structured and evidence-based datasets to unlock new
insights and accelerate drug research.
Learn more
Use our structured and evidence-based datasets to unlock new insights and accelerate drug research.
Learn more
Kind
Protein
Organism
Humans
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. [Article]
  2. Kantarjian HM, Jeha S, Gandhi V, Wess M, Faderl S: Clofarabine: past, present, and future. Leuk Lymphoma. 2007 Oct;48(10):1922-30. [Article]
  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. [Article]
  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. [Article]
  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. [Article]
Kind
Protein
Organism
Humans
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. [Article]
  2. Kantarjian HM, Jeha S, Gandhi V, Wess M, Faderl S: Clofarabine: past, present, and future. Leuk Lymphoma. 2007 Oct;48(10):1922-30. [Article]
  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. [Article]
  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. [Article]
  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. [Article]
Kind
Protein
Organism
Humans
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. [Article]
  2. Kantarjian HM, Jeha S, Gandhi V, Wess M, Faderl S: Clofarabine: past, present, and future. Leuk Lymphoma. 2007 Oct;48(10):1922-30. [Article]
  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. [Article]
  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. [Article]
  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. [Article]
Kind
Nucleotide
Organism
Humans
Pharmacological action
Yes
Actions
Other/unknown
DNA is the molecule of heredity, as it is responsible for the genetic propagation of most inherited traits. It is a polynucleic acid that carries genetic information on cell growth, division, and function. DNA consists of two long strands of nucleotides twisted into a double helix and held together by hydrogen bonds. The sequence of nucleotides determines hereditary characteristics. Each strand serves as the template for subsequent DNA replication and as a template for mRNA production, leading to protein synthesis via ribosomes.
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. [Article]
  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. [Article]
  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. [Article]
  4. Kantarjian HM, Jeha S, Gandhi V, Wess M, Faderl S: Clofarabine: past, present, and future. Leuk Lymphoma. 2007 Oct;48(10):1922-30. [Article]
  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. [Article]
  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. [Article]
  7. Hartman WR, Hentosh P: The antileukemia drug 2-chloro-2'-deoxyadenosine: an intrinsic transcriptional antagonist. Mol Pharmacol. 2004 Jan;65(1):227-34. [Article]
Kind
Protein
Organism
Humans
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. [Article]
  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. [Article]
  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. [Article]
  4. Hartman WR, Hentosh P: The antileukemia drug 2-chloro-2'-deoxyadenosine: an intrinsic transcriptional antagonist. Mol Pharmacol. 2004 Jan;65(1):227-34. [Article]
Kind
Protein
Organism
Humans
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. [Article]
Kind
Protein
Organism
Humans
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. [Article]
Kind
Protein
Organism
Humans
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. [Article]
Kind
Protein
Organism
Humans
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. [Article]
Kind
Protein
Organism
Humans
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. [Article]
  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. [Article]
  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. [Article]
  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. [Article]
  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. [Article]

Enzymes

Kind
Protein
Organism
Humans
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. [Article]
  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. [Article]
  3. Kantarjian HM, Jeha S, Gandhi V, Wess M, Faderl S: Clofarabine: past, present, and future. Leuk Lymphoma. 2007 Oct;48(10):1922-30. [Article]
  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. [Article]
  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. [Article]
  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. [Article]

Transporters

Kind
Protein
Organism
Humans
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. [Article]
  2. FDA Approved Drug Products: MAVENCLAD (cladribine) tablets, for oral use (December 2023) [Link]
Kind
Protein
Organism
Humans
Pharmacological action
Unknown
Actions
Substrate
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. [Article]
  2. FDA Approved Drug Products: MAVENCLAD (cladribine) tablets, for oral use (December 2023) [Link]
Kind
Protein
Organism
Humans
Pharmacological action
Unknown
Actions
Substrate
General Function
Xenobiotic-transporting atpase activity
Specific Function
Energy-dependent efflux pump responsible for decreased drug accumulation in multidrug-resistant cells.
Gene Name
ABCB1
Uniprot ID
P08183
Uniprot Name
Multidrug resistance protein 1
Molecular Weight
141477.255 Da
References
  1. FDA Approved Drug Products: MAVENCLAD (cladribine) tablets, for oral use (December 2023) [Link]
Kind
Protein
Organism
Humans
Pharmacological action
Unknown
General Function
Nucleoside transmembrane transporter activity
Specific Function
Mediates both influx and efflux of nucleosides across the membrane (equilibrative transporter). It is sensitive (ES) to low concentrations of the inhibitor nitrobenzylmercaptopurine riboside (NBMPR...
Gene Name
SLC29A1
Uniprot ID
Q99808
Uniprot Name
Equilibrative nucleoside transporter 1
Molecular Weight
50218.805 Da
References
  1. FDA Approved Drug Products: MAVENCLAD (cladribine) tablets, for oral use (December 2023) [Link]

Drug created at June 13, 2005 13:24 / Updated at May 19, 2024 10:11