Folate Antagonists

Abstract

Overview Folic acid antagonists (antifols) are cytotoxic drugs used as antineoplastic, antimicrobial, anti‐inflammatory, and immune‐suppressive agents. While several folate antagonists have been developed, methotrexate (4‐amino‐4‐deoxy‐10‐ N ‐methyl‐pteroylglutamic acid; MTX) is the antifol with the most extensive history and widest spectrum of use. MTX remains an essential drug in curative chemotherapy regimens used to treat patients with acute lymphoblastic leukemia, osteosarcoma, and choriocarcinoma and is an important agent in the therapy of patients with lymphoma, breast cancer, bladder cancer, and head and neck cancer. In addition, it is used for patients with nonmalignant diseases such as rheumatoid arthritis, psoriasis, autoimmune diseases, and graft versus host disease. This chapter will review the clinical use of and the metabolism of MTX and discuss structurally related folate antagonists that have been developed to overcome resistance or have alternate intracellular targets.