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Record Information
Version1.0
Creation Date2014-09-11 05:16:01 UTC
Update Date2016-11-09 01:09:12 UTC
Accession NumberCHEM003731
Identification
Common NameCladribine
ClassSmall Molecule
DescriptionAn antineoplastic agent used in the treatment of lymphoproliferative diseases including hairy-cell leukemia.
Contaminant Sources
  • HMDB Contaminants - Urine
  • STOFF IDENT Compounds
  • T3DB toxins
  • ToxCast & Tox21 Chemicals
Contaminant Type
  • Amine
  • Antineoplastic Agent
  • Drug
  • Ether
  • Immunosuppressive Agent
  • Metabolite
  • Organic Compound
  • Organochloride
  • Synthetic Compound
Chemical Structure
Thumb
Synonyms
ValueSource
(2R,3S,5R)-5-(6-Amino-2-chloropurin-9-yl)-2-(hydroxymethyl)oxolan-3-olChEBI
2-CdAChEBI
2-Chloro-2'-deoxy-beta-adenosineChEBI
2-Chloro-6-amino-9-(2-deoxy-beta-D-erythro-pentofuranosyl)purineChEBI
2-Chloro-deoxyadenosineChEBI
2-ChlorodeoxyadenosineChEBI
2ClAdoChEBI
CladribinaChEBI
CladribinumChEBI
CldAdoChEBI
LeustatinKegg
MavencladKegg
2-Chloro-2'-deoxy-b-adenosineGenerator
2-Chloro-2'-deoxy-β-adenosineGenerator
2-Chloro-6-amino-9-(2-deoxy-b-D-erythro-pentofuranosyl)purineGenerator
2-Chloro-6-amino-9-(2-deoxy-β-D-erythro-pentofuranosyl)purineGenerator
2-Chloro-2'-deoxyadenosineHMDB
ChlorodeoxyadenosineHMDB
2'-Deoxy-2-chloroadenosineHMDB
Chemical FormulaC10H12ClN5O3
Average Molecular Mass285.687 g/mol
Monoisotopic Mass285.063 g/mol
CAS Registry Number4291-63-8
IUPAC Name(2R,3S,5R)-5-(6-amino-2-chloro-9H-purin-9-yl)-2-(hydroxymethyl)oxolan-3-ol
Traditional Namecladribine
SMILESNC1=C2N=CN([C@H]3C[C@H](O)[C@@H](CO)O3)C2=NC(Cl)=N1
InChI IdentifierInChI=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
InChI KeyPTOAARAWEBMLNO-KVQBGUIXSA-N
Chemical Taxonomy
Description belongs to the class of organic compounds known as purine 2'-deoxyribonucleosides. Purine 2'-deoxyribonucleosides are compounds consisting of a purine linked to a ribose which lacks a hydroxyl group at position 2.
KingdomOrganic compounds
Super ClassNucleosides, nucleotides, and analogues
ClassPurine nucleosides
Sub ClassPurine 2'-deoxyribonucleosides
Direct ParentPurine 2'-deoxyribonucleosides
Alternative Parents
Substituents
  • Purine 2'-deoxyribonucleoside
  • 6-aminopurine
  • Imidazopyrimidine
  • Purine
  • Aminopyrimidine
  • 2-halopyrimidine
  • Halopyrimidine
  • N-substituted imidazole
  • Aryl chloride
  • Aryl halide
  • Pyrimidine
  • Imidolactam
  • Tetrahydrofuran
  • Heteroaromatic compound
  • Imidazole
  • Azole
  • Secondary alcohol
  • Oxacycle
  • Azacycle
  • Organoheterocyclic compound
  • Organohalogen compound
  • Primary alcohol
  • Primary amine
  • Amine
  • Alcohol
  • Organic nitrogen compound
  • Hydrocarbon derivative
  • Organopnictogen compound
  • Organic oxygen compound
  • Organochloride
  • Organonitrogen compound
  • Organooxygen compound
  • Aromatic heteropolycyclic compound
Molecular FrameworkAromatic heteropolycyclic compounds
External Descriptors
Biological Properties
StatusDetected and Not Quantified
OriginExogenous
Cellular Locations
  • Cytoplasm
  • Extracellular
  • Membrane
Biofluid LocationsNot Available
Tissue LocationsNot Available
PathwaysNot Available
ApplicationsNot Available
Biological RolesNot Available
Chemical RolesNot Available
Physical Properties
StateSolid
AppearanceWhite powder.
Experimental Properties
PropertyValue
Melting Point215°C
Boiling PointNot Available
Solubility6.35e+00 g/L
Predicted Properties
PropertyValueSource
Water Solubility6.35 g/LALOGPS
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 ŲChemAxon
Rotatable Bond Count2ChemAxon
Refractivity67.18 m³·mol⁻¹ChemAxon
Polarizability25.93 ųChemAxon
Number of Rings3ChemAxon
Bioavailability1ChemAxon
Rule of FiveYesChemAxon
Ghose FilterYesChemAxon
Veber's RuleYesChemAxon
MDDR-like RuleYesChemAxon
Spectra
Spectra
Spectrum TypeDescriptionSplash Key
Predicted GC-MSPredicted GC-MS Spectrum - GC-MSsplash10-0006-9140000000-2241274903b14d6388f8View in MoNA
Predicted GC-MSPredicted GC-MS Spectrum - GC-MS (2 TMS)splash10-006x-9003100000-a89891be7a06bbd5506cView in MoNA
LC-MS/MSLC-MS/MS Spectrum - LC-ESI-qTof , Positivesplash10-00di-1910000000-ab013e8ee7a199f7832aView in MoNA
LC-MS/MSLC-MS/MS Spectrum - LC-ESI-qTof , Positivesplash10-00e9-2900000000-e03a0a91db8b01dbf975View in MoNA
LC-MS/MSLC-MS/MS Spectrum - , positivesplash10-00di-1910000000-ab013e8ee7a199f7832aView in MoNA
LC-MS/MSLC-MS/MS Spectrum - , positivesplash10-00e9-2900000000-e03a0a91db8b01dbf975View in MoNA
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 10V, Positivesplash10-00di-0920000000-8e9ebddc65823aa84924View in MoNA
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 20V, Positivesplash10-00di-0900000000-0b29ceb8b9b509f8d741View in MoNA
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 40V, Positivesplash10-00di-0900000000-f0f21af02a8d1d299e4aView in MoNA
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 10V, Negativesplash10-00e9-0290000000-7a1cc2a1753c44b0a43dView in MoNA
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 20V, Negativesplash10-014i-0910000000-7d61665b0d4c6756760fView in MoNA
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 40V, Negativesplash10-00lr-1900000000-345fc7c0125888e844c5View in MoNA
Toxicity Profile
Route of ExposureOral bioavailability is 34 to 48%.
Mechanism of ToxicityCladribine 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-2ду_-deoxyadenosine 5ду_-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.
MetabolismMetabolized in all cells with deoxycytidine kinase activity to 2-chloro-2'-deoxyadenosine-5'-triphosphate Half Life: 5.4 hours
Toxicity ValuesNot Available
Lethal DoseNot Available
Carcinogenicity (IARC Classification)No indication of carcinogenicity to humans (not listed by IARC).
Uses/SourcesFor 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.
Minimum Risk LevelNot Available
Health EffectsNot Available
SymptomsSymptoms of overdose include irreversible neurologic toxicity (paraparesis/quadriparesis), acute nephrotoxicity, and severe bone marrow suppression resulting in neutropenia, anemia and thrombocytopenia.
TreatmentNot Available
Concentrations
Not Available
DrugBank IDDB00242
HMDB IDHMDB0014387
FooDB IDNot Available
Phenol Explorer IDNot Available
KNApSAcK IDNot Available
BiGG IDNot Available
BioCyc IDNot Available
METLIN IDNot Available
PDB IDCL9
Wikipedia LinkCladribine
Chemspider ID19105
ChEBI ID567361
PubChem Compound ID20279
Kegg Compound IDNot Available
YMDB IDNot Available
ECMDB IDNot 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.

MSDSLink
General References
1. 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.
2. Kantarjian HM, Jeha S, Gandhi V, Wess M, Faderl S: Clofarabine: past, present, and future. Leuk Lymphoma. 2007 Oct;48(10):1922-30.
3. 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.
4. 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.
5. 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.
6. 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.
7. 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.
8. Dimopoulos MA, Weber DM, Kantarjian H, Keating M, Alexanian R: 2Chlorodeoxyadenosine therapy of patients with Waldenstrom macroglobulinemia previously treated with fludarabine. Ann Oncol. 1994 Mar;5(3):288-9.
9. https://www.ncbi.nlm.nih.gov/pubmed/?term=17526755
10. https://www.ncbi.nlm.nih.gov/pubmed/?term=18570408
11. https://www.ncbi.nlm.nih.gov/pubmed/?term=26024233