Drug intelligence / Profile preview

5-fluorouracil + allopurinol + dipyridamole + folinic acid

Development stage
Unknown
Lead developer
GSK
Modality
Small Interfering RNA (siRNA) → Small RNA Therapeutics → RNA Therapeutics → Nucleic Acid Therapeutics, MicroRNA (miRNA) → Small RNA Therapeutics → RNA Therapeutics → Nucleic Acid Therapeutics, Antisense Oligonucleotides (ASOs) → Long RNA Therapeutics → RNA Therapeutics → Nucleic Acid Therapeutics, Antisense DNA → DNA Therapeutics → Nucleic Acid Therapeutics, Small Molecules
Administration
Intravenous, Oral
01

Overview

This is a combination regimen consisting of four agents: - **5-fluorouracil (5-FU):** A pyrimidine analog antimetabolite that inhibits thymidylate synthase, disrupting DNA synthesis and leading to cell death. It is widely used as a chemotherapeutic agent in various solid tumors. - **Allopurinol:** A xanthine oxidase inhibitor primarily used to reduce uric acid levels but also investigated for its ability to modulate the toxicity profile of 5-FU by reducing myelosuppression and gastrointestinal side effects[2][5]. - **Dipyridamole:** An antiplatelet agent and nucleoside transport inhibitor. In this context, it has been studied for its potential to modulate the cytotoxicity of 5-FU by inhibiting cellular uptake of nucleosides, potentially enhancing or altering the effect of chemotherapy[6][8]. - **Folinic acid (leucovorin):** A reduced form of folic acid that enhances the binding of 5-FU to thymidylate synthase, thereby increasing its cytotoxic efficacy. This combination has been explored in clinical trials for advanced refractory malignancies such as colorectal cancer. The rationale is based on preclinical evidence suggesting synergistic or modulatory effects among these agents; however, clinical studies have shown mixed results regarding efficacy and toxicity. Notably, adding dipyridamole did not significantly improve outcomes over standard regimens with 5-FU/folinic acid alone[6][8]. Allopurinol may provide some protection against high-dose 5-FU toxicity but does not necessarily improve response rates[2]. This regimen remains investigational and is not an established standard therapy.

Other names
5-FU + allopurinol + dipyridamole + folinic acidfluorouracil + allopurinol + dipyridamole + leucovorin
02

Targets

DHFR (Dihydrofolate reductase)ENT1 (Solute carrier family 29 member 1)TS (Thymidylate synthase)XO (Xanthine Oxidoreductase)ENT (Equilibrative nucleoside transporter family)

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