XYZ-I-71

XYZ-I-71 is a novel 5-fluorouracil (5-FU) analog developed for the treatment of pancreatic cancer. It is synthesized by introducing a tetrahydrofuran ring onto 5-fluorocytosine (a precursor of 5-FU) and conjugating it with octanoyl chloride. This modification is designed to improve the metabolic stability and cytotoxic profile of 5-FU, which is often limited by systemic instability and drug resistance. In preclinical studies, XYZ-I-71 demonstrated significant antiproliferative activity against MiaPaCa-2, PANC-1, and BxPC-3 pancreatic cancer cell lines, showing a 2-fold increased cytotoxic effect over gemcitabine in MiaPaCa-2 cells. It also exhibits improved metabolic stability in human liver microsomes compared to 5-FU, with approximately 80% of the compound remaining intact after two hours of exposure. Mechanistically, it induces apoptosis and inhibits cell migration, associated with the modulation of PARP, BAX, and p53 expression.