| Autor: |
Catherine, Adam, Thomas L, Bray, Ana M, Pérez-López, Ee Hong, Tan, Belén, Rubio-Ruiz, Daniel J, Baillache, Douglas R, Houston, Mark J, Salji, Hing Y, Leung, Asier, Unciti-Broceta |
| Rok vydání: |
2022 |
| Předmět: |
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| Zdroj: |
Journal of medicinal chemistry. 65(1) |
| ISSN: |
1520-4804 |
| Popis: |
5-Fluorouracil (5-FU) is an antineoplastic antimetabolite that is widely administered to cancer patients by bolus injection, especially to those suffering from colorectal and pancreatic cancer. Because of its suboptimal route of administration and dose-limiting toxicities, diverse 5-FU prodrugs have been developed to confer oral bioavailability and increase the safety profile of 5-FU chemotherapy regimens. Our contribution to this goal is presented herein with the development of a novel palladium-activated prodrug designed to evade the metabolic machinery responsible for 5-FU anabolic activation and catabolic processing. The new prodrug is completely innocuous to cells and highly resistant to metabolization by primary hepatocytes and liver S9 fractions (the main metabolic route for 5-FU degradation), whereas it is rapidly converted into 5-FU in the presence of a palladium (Pd) source. |
| Databáze: |
OpenAIRE |
| Externí odkaz: |
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