O O Cys

FIGURE 2.36 Covalent inactivation of phosphoribosylformylglycinamidine synthase by azaserine and DON.

response of choriocarcinoma to DON, although in general these compounds are too toxic.

6.4. Inhibitors of 5-aminoimidazole-4-carboxamide ribonucleotide formyltransferase

Some antifolate drugs (e.g., MTX, permetrexed) inhibit this enzyme, although it is not their primary target.

6.5. Thiopurines and related compounds

Among nonnatural purine derivatives assayed as antitumor agents, 6-mercapto-purine (MP) and 6-thioguanine (TG) are the most active. These compounds are among the oldest cancer chemotherapeutic drugs in clinical use; MP is used for lymphoblastic and myeloblastic leukemias, and the more toxic TG is employed for the treatment of acute non-lymphocytic leukemia.

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