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Amifostine is a prodrug that through dephosphorylation by alkaline phosphatase is converted to an active thiol, WR 1065 that has free radical scavenging, DNA protective, and hypoxia inducing activities. Because of the differential expression of alkaline phosphatase in normal versus neoplastic tissues, the cytoprotection conferred by amifostine is selective, enabling as much as 100-fold greater accumulation of WR 1065 in normal tissues than in tumor cells. Amifostine has been used to reduce toxicity in normal tissues exposed to radiation or chemotherapeutic agents. In mouse fibroblasts and various cancer cells, amifostine (IC50 = 4 mM) has been shown to activate p53 protein, to induce the expression of the cyclin-dependent kinase inhibitor p21, and to arrest cells at the G1/S transition through a p53-dependent mechanism.

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