page_title: Fluorodeoxyuridylate
section_title: 5-FU and floxuridine, precursors of FdUMP
hierarchical_section_title: Fluorodeoxyuridylate / Function / 5-FU and floxuridine, precursors of FdUMP
caption_attribution_description: English: FdUMP chemical structure
context_page_description: Fluorodeoxyuridylate, also known as FdUMP, 5-Fluoro-2'-deoxyuridylate, or 5-Fluoro-2'-deoxyuridine 5'-monophosphate sodium salt, is a molecule formed in vivo from 5-fluorouracil or 5-fluorodeoxyuridin.
  FdUMP acts as a suicide inhibitor of thymidylate synthase. By inhibiting the deoxynucleotide biosynthesis, FdUMP stops the rapidly proliferation of fast-growing death cancer tumors, and it is therefore widely used as a cancer treatment.
  The Fluorouracil molecule, performs as a substrate during part of the catalytic cycle, and it is only during the synthesis of thymine from uridine, when it is combined with other molecules to form 5-FdUMP to produce an irreversible inhibition of the thymidylate synthase functions. This inhibition leads to an imbalance of the nucleotide grouping, stopping the DNA synthesis.
context_section_description: The prodrug 5-fluorouracil (5-FU) was the first antimetabolite used as a TS inhibitor. It penetrates the cell through the same facilitated transport mechanism as the uracil, due to the analogy between the two molecules (similar shape and size). The transporter recognizes 5-FU as an endogenous molecule. Subsequently, the uracil and 5-FU compete to enter the cellular interior and it is the molecule with the highest concentration that will enter in greater abundance.
  For 5-FU to inhibit TS by its mechanism of action, it must first be bioactivated through a series of reactions:
  5-FU ends up becoming 5-FdUMP (the active form of the drug), that is, the one that is really going to be recognized by the TS and thus be able to inhibit it.
  In addition, the bioactivation pathway followed by 5-FU is the same as that followed by the endogenous substrate (uracil), using the same enzymes to bioactivate itself.
  On the other hand, floxuridine (5-FUdR) is another prodrug that also inhibits TS; although its bioactivation process is much simpler than 5-FU, as it only has to be phosphorylated to become 5-FdUMP.
caption: FdUMP Chemical structure
exif: {}