Projects per year
and dose limiting toxicities, a diversity of 5-FU prodrugs has 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-activatable 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 (main metabolic route for 5-FU degradation), whereas it is rapidly converted into 5-FU in the presence of a Palladium (Pd) source. In vivo PK analysis shows the prodrug is rapidly and completely absorbed after oral administration and exhibits longer half-life than 5-FU. In vivo efficacy studies in a xenograft colon cancer model served to prove, for the first time, that orally-administered prodrugs can be locally-converted into active drugs by intratumorally-inserted Pd-implants.
FingerprintDive into the research topics of 'A 5-FU precursor designed to evade anabolic and catabolic drug pathways and activated by Pd chemistry in vitro and in vivo'. Together they form a unique fingerprint.
- 2 Finished
1/07/18 → 31/08/19
Locally-Controlled Activation of Chemotherapeutics by Palladium Catalysis as a Novel Anticancer Technology
1/04/16 → 30/09/21