Thymidylate synthase inhibitor

From Wikipedia, the free encyclopedia

Thymidylate synthase inhibitors are chemical agents which inhibit the enzyme thymidylate synthase and have potential as an anticancer chemotherapy.[1] This inhibition prevents the methylation of C5 of deoxyuridine monophosphate (dUMP) thereby inhibiting the synthesis of deoxythymidine monophosphate (dTMP). The downstream effect is promotion of cell death because cells would not be able to properly undergo DNA synthesis if they are lacking dTMP, a necessary precursor to dTTP.[2] Five agents were in clinical trials in 2002: raltitrexed, pemetrexed, nolatrexed, ZD9331, and GS7904L.[3]

Examples include


  1. ^ Jackman AL, Calvert AH (November 1995). "Folate-based thymidylate synthase inhibitors as anticancer drugs". Annals of Oncology. 6 (9): 871–81. doi:10.1093/oxfordjournals.annonc.a059353. PMID 8624289.
  2. ^ Ackland SP, Clarke SJ, Beale P, Peters GJ (December 2006). "Thymidylate synthase inhibitors". Update on Cancer Therapeutics. 1 (4): 403–427. doi:10.1016/j.uct.2006.09.001.
  3. ^ "Thymidylate synthase inhibitors as anticancer agents: from bench to bedside". Retrieved 2009-01-28.
  4. ^ Liu Y, Wu W, Hong W, Sun X, Wu J, Huang Q (April 2014). "Raltitrexed-based chemotherapy for advanced colorectal cancer". Clinics and Research in Hepatology and Gastroenterology. 38 (2): 219–25. doi:10.1016/j.clinre.2013.11.006. PMID 24388340.
  5. ^ Papamichael D (1999). "The use of thymidylate synthase inhibitors in the treatment of advanced colorectal cancer: current status". The Oncologist. 4 (6): 478–87. doi:10.1634/theoncologist.4-6-478. PMID 10631692.
  6. ^ Gibbs DD, Theti DS, Wood N, Green M, Raynaud F, Valenti M, Forster MD, Mitchell F, Bavetsias V, Henderson E, Jackman AL (December 2005). "BGC 945, a novel tumor-selective thymidylate synthase inhibitor targeted to alpha-folate receptor-overexpressing tumors". Cancer Research. 65 (24): 11721–8. doi:10.1158/0008-5472.CAN-05-2034. PMID 16357184.
  7. ^ Ricart AD, Berlin JD, Papadopoulos KP, Syed S, Drolet DW, Quaratino-Baker C, Horan J, Chick J, Vermeulen W, Tolcher AW, Rowinsky EK, Rothenberg ML (December 2008). "Phase I, pharmacokinetic and biological correlative study of OSI-7904L, a novel liposomal thymidylate synthase inhibitor, and cisplatin in patients with solid tumors". Clinical Cancer Research. 14 (23): 7947–55. doi:10.1158/1078-0432.CCR-08-0864. PMID 19047127.