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

Nelarabine的IC50在T系和B系血统中分别比ARAC高出25倍和113倍。T-ALL细胞对Nelarabine的敏感性是B系血统的八倍，但两者之间有相当程度的重叠。在T系和B系血统细胞系中，NEL的功效分别比ARAC低25倍和113倍。[1] Nelarabine通过抑制DNA合成并诱导敏感细胞凋亡发挥作用。[2] Nelarabine展现了显著的抗肿瘤活性并且具有可接受的毒性。[3]

Nelarabine的血浆AUC为2.82 mM分钟，ara-G的血浆AUC为20 mM分钟。Nelarabine在血浆中的末端半衰期为25分钟，清除率为42 mL/分钟/kg，中心分布体积为1.1 L/kg。ara-G在血浆中的末端半衰期为182分钟，中心分布体积为1.4 L/kg。在CSF中，Nelarabine的末端半衰期为77分钟，而ara-G的为232分钟。AUCcsf:AUCplasma对于Nelarabine为29%，对于ara-G为23%。由于Nelarabine和ara-G有相对较短的半衰期，因此通过每日输注不会累积。[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)