Thymidylate synthase inhibitors.

摘要: Thymidylate synthase (TS) is a critical enzyme for DNA replication and cell growth because it the only de novo source of thymine nucleotide precursors synthesis. TS primary target 5-fluorouracil (5-FU), which has been used cancer treatment more than 40 years. However, dissatisfaction with overall activity 5-FU against major cancers, recognition that still remains an attractive anticancer drugs its central position in pathway synthesis, led to search new inhibitors structurally analogous 5,10-methylenetetrahydrofolate, second substrate TS. inhibitory antifolates developed date are various stages clinical evaluation ZD 1694 ZD9331 (Astra-Zeneca, London, UK), (Eli Lilly, Indianapolis, IN), LY231514 (BW1843U89 (Glaxo-Wellcome, Research Triangle Park, NC), AG337 AG331 (Agouron, La Jolla, CA). Although each these compounds as intracellular site action, they differ propensity polyglutamylation transport by reduced folate carrier. also secondary enzymes. As result, compound likely have different spectrum antitumor toxicity. This review will summarize development properties this class inhibitors.