Nelarabine

Healthy adult male rhesus monkeys

Nelarabine plus Doxorubicin, Cyclophosphamide, Cytarabine, Dexamethasone, Methotrexate or Vincristine has entered in a phase II clinical trial in the treatment of leukemia, acute lymphoblastic leukemia, and lymphoblastic lymphoma.

Nelarabine (Arranon, 506U78) is a purine nucleoside analog and DNA synthesis inhibitor for HSB2 cell lines and ALL-SIL cell lines with IC50 of 0.13 ug/mL and 0.37 ug/mL, respectively.

Nelarabine is rapidly converted into ara-G through demethoxylation by adenosine deaminase.

0.13 ug/mL, 0.13 ug/mL, 0.13 ug/mL, 0.13 ug/mL, 0.13 ug/mL, 0.13 ug/mL

The Nelarabine plasma AUC is 2.82 mM minutes and the ara-G plasma AUC is 20 mM minutes. The terminal half-life of Nelarabine in plasma is 25 min, clearance is 42 mL/minutes/kg, and central volume of distribution is 1.1 L/kg. The terminal half-life of ara-G in plasma is 182 minutes and the central volume of distribution is 1.4 L/kg. In CSF the terminal half-life of Nelarabine is 77 minutes and of ara-G is 232 minutes. The AUCcsf:AUCplasma is 29 % for Nelarabine and 23 % for ara-G. Nelarabine and ara-G do not accumulate with daily infusions because of their relatively short half-lives. [4]

HSB2, ALL-SIL, JURKAT and PER-255 cell lines are tested for drug resistance using the MTT assay. Nelarabine are incubated over 4 days, with concentration tested in triplicate. The IC50 (drug concentration that inhibits cell growth by 50%) is used as the measure of drug resistance. Data represent the average of 2–6 experiments performed on separate occasions. In cases where 50% cytotoxicity is not achieved by even the highest dose in a particular experiment, the IC50 is recorded as double the highest concentration tested.

Nelarabine (Arranon) Chemical Structure

2 years -20CPowder, 2 weeks4Cin DMSO, 2 months-80Cin DMSO