Nelarabine is a novel and prodrug of ara-G (9-β-d-arabinofuranosylguanine), and it is used to treat T-cell lymphoblastic lymphoma (T-LBL) and T-cell acute lymphoblastic leukemia (T-ALL), which don’t have response after treatment with 2 chemotherapy regimens.[1]

It acts as an inhibitor by inhibiting DNA synthesis and as an inducer by inducing apoptosis in malignant cells. Nelarabine requires demethylation by adenosine deaminase (ADA) in plasma to form the active compound, ara-G. Intracellular by deoxyguanosine kinase and deoxycytidine kinase phosphorylate ara-G to its triphosphate form, ara-GTP. Inside the cell exposure to ara-GTP is much higher than the exposure to ara-G or nelarabine. The substitution of ara-GTP for GTP leads to inhibition of DNA synthesis resulting in cell death by apoptosis. This process is lethal to malignant T cells, as it is to other rapidly replicating cells.[2]

References:
[1] Cohen MH, Johnson JR, Massie T, et al. Approval summary: nelarabine for the treatment of T-cell lymphoblastic leukemia/lymphoma. Clin Cancer Res. September 2006. 18:5329–35.
[2] Yesid Alvarado, Mary Alma Welch, Ronan Swords, John Bruzzi, Ellen Schlette, Francis J. Giles. Nelarabine activity in acute biphenotypic leukemia. Leukemia Research. November 2007. 31(11): 1600-1603.