2'-DCF - General Information:
A potent inhibitor of adenosine deaminase. The drug is effective in the treatment of many lymphoproliferative malignancies, particularly hairy-cell leukemia. It is also synergistic with some other antineoplastic agents and has immunosuppressive activity.
Pharmacology of 2'-DCF
2'-DCF is an antineoplastic anti-metabolite used in the treatment of several forms of leukemia including acute nonlymphocytic leukemia and hairy cell leukemia. Anti-metabolites masquerade as purine or pyrimidine - which become the building blocks of DNA. They prevent these substances becoming incorporated in to DNA during the "S" phase (of the cell cycle), stopping normal development and division. It is a 6-thiopurine analogue of the naturally occurring purine bases hypoxanthine and guanine. Intracellular activation results in incorporation into DNA as a false purine base. An additional cytotoxic effect is related to its incorporation into RNA. Cytotoxicity is cell cycle phase-specific (S-phase).
2'-DCF for patients
Interactions with cylcopholsphamide, fludarabine and vidarabine
Patients with severe pre-existing infections should not receive this drug. Contraindicated in patients with severe renal impairment
Additional information about 2'-DCF
2'-DCF Indication: For the treatment of hairy cell leukaemia refractory to alpha interferon.
Mechanism Of Action: 2'-DCF is a potent transition state inhibitor of adenosine deaminase (ADA), the greatest activity of which is found in cells of the lymphoid system. T-cells have higher ADA activity than B-cells, and T-cell malignancies have higher activity than B-cell malignancies. The cytotoxicity that results from prevention of catabolism of adenosine or deoxyadenosine is thought to be due to elevated intracellular levels of dATP, which can block DNA synthesis through inhibition of ribonucleotide reductase. Intracellular activation results in incorporation into DNA as a false purine base. An additional cytotoxic effect is related to its incorporation into RNA. Cytotoxicity is cell cycle phase-specific (S-phase).
Drug Interactions: Not Available
Food Interactions: Not Available
Generic Name: Pentostatin
Synonyms: Not Available
Drug Category: Immunosuppressive Agents; Antibiotics; Antineoplastic Agents
Drug Type: Small Molecule; Approved; Investigational
Other Brand Names containing Pentostatin: 2'-DCF; 2'-Deoxycoformycin; 2'-Dexoycoformycin; Co-V; Co-Vidarabine; Covidarabine; Deaminase Inhibitor; Deoxycoformycin; Nipent; PD-ADI; Vidarbine; Vira a Deaminase Inhibitor.
Absorption: Not absorbed orally, crosses blood brain barrier.
Toxicity (Overdose): LD50=128 mg/kg (mouse), side effects include lethargy, rash, fatigue, nausea and myelosuppression.
Protein Binding: 4%
Biotransformation: Primarily hepatic, but only small amounts are metabolized.
Half Life: 5.7 hours (with a range between 2.6 and 16 hrs)
Dosage Forms of 2'-DCF: Not Available
Chemical IUPAC Name: (8R)-3-[4-hydroxy-5-(hydroxymethyl)oxolan-2-yl]-7,8-dihydro-4H-imidazo[4,5-f][1,3]diazepin-8-ol
Chemical Formula: C11H16N4O4
Pentostatin on Wikipedia: http://en.wikipedia.org/wiki/Pentostatin
Organisms Affected: Humans and other mammals