Nelarabine (GW 506U78) is a purine nucleoside analog and DNA synthesis inhibitor with IC50 from 0.067-2.15 μM in tumor cells.

DNA synthesis (PER-255 cells):0.067-2.15 μM

The IC50 of Nelarabine is 25-fold and 113-fold higher than ARAC in T- and B-lineage, respectively. T-ALL cells are eightfold more sensitive to Nelarabine than B-lineage but there is considerable overlap. The efficacy of NEL in T-lineage and B-lineage cell lines is 25-fold and 113-fold less than ARAC, respectively. [1] Nelarabine acts by inhibiting DNA synthesis and inducing apoptosis in susceptible cells. [2]Nelarabine demonstrated significant antineoplastic activity with acceptable toxicity. [3]

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.(Only for Reference)