title: Methodology for the rational development of methotrexate analogs in the clinic.
abstract: This paper suggests a development plan for antifolate analogs, based upon disease classifications that the National Cancer Institute has successfully utilized for the development of anthracycline and platinum analogs. Diseases are classified according to the role of the parent compound in standard therapy: 1) those in which methotrexate is an important component of standard treatment strategies that have state-of-the-art effectiveness; 2) those in which methotrexate has antitumor activity but no clear role in standard state-of-the-art treatment strategies; and 3) those in which methotrexate has insufficient activity to warrant its use alone or in combination. Developmental plans are specified for each of these disease classes. Trimetrexate is used as a specific example for these plans, although this method of drug development is equally applicable to other methotrexate analogs.
mesh_terms: D000903:Antibiotics, Antineoplastic; D004341:Drug Evaluation; D005493:Folic Acid Antagonists; D006801:Humans; D008727:Methotrexate / Q000031:analogs & derivatives*; D009279:Naphthacenes; D009369:Neoplasms / Q000188:drug therapy*; D010984:Platinum
chemical_list: D000903:Antibiotics, Antineoplastic; D005493:Folic Acid Antagonists; D009279:Naphthacenes; D010984:Platinum; D008727:Methotrexate