Cladribine: Not just another purine analogue?

Stephen Spurgeon, Margaret Yu, John D. Phillips, Elliot M. Epner

Research output: Contribution to journalArticle

40 Citations (Scopus)

Abstract

Cladribine was synthesized as a purine analogue drug that inhibited adenosine deaminase. It received FDA approval in the 1980s for treatment of hairy cell leukemia. Given its toxicity towards lymphocytes and its corresponding immunosuppressive effects, it has been studied and found efficacious in a variety of hematologic malignancies and autoimmune conditions, most recently multiple sclerosis. This review highlights pharmacological, toxicological and clinical data for the use of cladribine. It also discusses existing and new mechanisms that may contribute to its unique clinical activity. Emerging data show that in addition to its known purine nucleoside analogue activity, cladribine possesses epigenetic properties, inhibiting S-adenosylhomocysteine hydrolase and DNA methylation. This may contribute to its efficacy and highlights the importance of studying combination therapy with other epigenetic or targeted agents. Clinical trials are underway in a variety of malignant and nonmalignant conditions.

Original languageEnglish (US)
Pages (from-to)1169-1181
Number of pages13
JournalExpert Opinion on Investigational Drugs
Volume18
Issue number8
DOIs
StatePublished - Aug 2009

Fingerprint

Cladribine
Epigenomics
Adenosylhomocysteinase
Purine Nucleosides
Hairy Cell Leukemia
Adenosine Deaminase
Hematologic Neoplasms
DNA Methylation
Immunosuppressive Agents
Toxicology
Multiple Sclerosis
Clinical Trials
Pharmacology
Lymphocytes
Pharmaceutical Preparations
purine
Therapeutics

Keywords

  • B-cell malignancies
  • Cladribine
  • Epigenetics
  • Hypomethylation
  • Multiple sclerosis
  • SAH hydrolase

ASJC Scopus subject areas

  • Pharmacology
  • Pharmacology (medical)

Cite this

Cladribine : Not just another purine analogue? / Spurgeon, Stephen; Yu, Margaret; Phillips, John D.; Epner, Elliot M.

In: Expert Opinion on Investigational Drugs, Vol. 18, No. 8, 08.2009, p. 1169-1181.

Research output: Contribution to journalArticle

Spurgeon, Stephen ; Yu, Margaret ; Phillips, John D. ; Epner, Elliot M. / Cladribine : Not just another purine analogue?. In: Expert Opinion on Investigational Drugs. 2009 ; Vol. 18, No. 8. pp. 1169-1181.
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