Abstract
For the last four decades, synthesis and testing of potentially active drugs (e.g., antimetabolites) have focused on structural modification of existing metabolites as precursors of DNA and RNA synthesis. In recent years, the focus has shifted to synthesis of target-specific agents. Thus, the current emphasis of drug development is directed at inhibiting specific target(s) expressed preferentially, if not exclusively, in tumor tissues, with the ultimate goal of improving the therapeutic efficacy and selectivity of these new agents. Preclinically, proof-of-principle studies were carried out in tumors with specific expression of the intended target. With the hope of translating preclinical findings to the design of implementation of clinical trials. Thymidylate synthase (TS) continues to be a critical target for 5-fluorouracil (5-FU) and its prodrugs, UFT/LV (Orzel), capecitabine (Xeloda), and S-1, primarily because this enzyme is essential for the synthesis of 2-deoxythymidine-5-monophosphate, a precursor for DNA synthesis. While fluoropyrimidine antimetabolites have other sites of action, antifolates ZD1694 (raltitrexed, Tomudex) and AG337 (Thymitag) are more specific and potent TS inhibitors. Thus, it is hoped that pronounced ...Continue Reading
Citations
Feb 26, 2013·Cancer Chemotherapy and Pharmacology·Jing-Ming ZhaiLong-Juan Zhang
Sep 15, 2005·Journal of Cancer Research and Clinical Oncology·Marina PavlakMarko Radacić
Nov 26, 2010·Molecular Biology Reports·Maria Wisniewska-JarosinskaAlina Morawiec-Sztandera
Jan 14, 2010·Annals of Nuclear Medicine·Ioannis Trigonis, Alan Jackson
May 2, 2009·Archives of Pharmacal Research·Anna B FishbeinChun-Su Yuan
Dec 13, 2007·Journal of Medicinal Chemistry·Aleem GangjeeRoy L Kisliuk
Oct 17, 2007·Journal of Biomolecular Structure & Dynamics·Abul HasnatJulie Andrews
Mar 25, 2008·DNA and Cell Biology·Tracey L H JasonJames Koropatnick
Apr 6, 2006·BMC Genomics·Yaguang XiJingfang Ju
Jul 12, 2014·BioMed Research International·Mohamed HassanNoriaki Sakuragi
Apr 29, 2010·Journal of Cancer Research and Clinical Oncology·Dimitrios J StravopodisGerassimos E Voutsinas
May 17, 2012·Brain Research Bulletin·Maha ELBeltagyPeter Wigmore
May 4, 2016·Oncoimmunology·Pierpaolo CorrealeMaria Grazia Cusi
Dec 7, 2010·Pharmacotherapy·Sachin R ShahSarah M Gressett Ussery
Nov 23, 2006·Toxicology in Vitro : an International Journal Published in Association with BIBRA·S GiudiceC Magnoni
Jan 7, 2011·Journal of Oncology·Muhammad Wasif SaifKostas Syrigos
Jun 3, 2015·Cancer Immunology, Immunotherapy : CII·Maria Grazia CusiPierpaolo Correale
Sep 11, 2007·Archives of Biochemistry and Biophysics·Per LindblomBjörn Glinghammar
Jan 19, 2016·Cell Death & Disease·S BaigT Kamarul
Jul 23, 2005·World Journal of Gastroenterology : WJG·Li FanZhao-Cai Yu
Mar 13, 2015·Oncotarget·Christoph BurdelskiStefan Steurer
Jul 13, 2017·PloS One·Pornthip ChaisawangJariya Umka Welbat
Jun 27, 2019·International Journal of Surgical Pathology·Rui GuoJun Yang
Mar 7, 2014·Clinical Cancer Research : an Official Journal of the American Association for Cancer Research·Bin LiAnnie L M Cheung
Aug 5, 2008·Clinical Cancer Research : an Official Journal of the American Association for Cancer Research·Marie-Christine Etienne-GrimaldiGérard Milano
Dec 19, 2020·Cancers·Anna KoumarianouMichalis V Karamouzis
Jun 24, 2009·Chemical Reviews·Mats Ljungman