Cladribine: not just another purine analogue?
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.
Spurgeon
Stephen
S
Oregon Health Sciences University, Medicine, 4130 Sam Jackson Park Road, Portland, OR 97239, USA.
Yu
Margaret
M
Phillips
John D
JD
Epner
Elliot M
EM
D058892:Adenosine Deaminase Inhibitors; D000970:Antineoplastic Agents / Q000009:adverse effects / Q000737:chemistry / Q000494:pharmacology* / Q000627:therapeutic use; D001327:Autoimmune Diseases / Q000188:drug therapy; D017338:Cladribine / Q000009:adverse effects / Q000737:chemistry / Q000493:pharmacokinetics / Q000494:pharmacology* / Q000627:therapeutic use; D002986:Clinical Trials as Topic; D019175:DNA Methylation / Q000187:drug effects; D006801:Humans; D015394:Molecular Structure; D009369:Neoplasms / Q000188:drug therapy; D011687:Purines / Q000737:chemistry*
D058892:Adenosine Deaminase Inhibitors; D000970:Antineoplastic Agents; D011687:Purines; D017338:Cladribine; C030985:purine