HµREL® possesses great adaptability to simulate different multi-tissue interactions. As a demonstration, HµREL® was tested on tegafur, a chemotherapeutic pro-drug. Tegafur itself is inactive and requires biotransformation by CYP450 enzymes present in the liver to generate the virulently cancer cell-killing metabolite 5’-fluorouracil (5-FU).
U.S. Patent No’s. 5,612,188; 7,288,405; 8,030,061; other patents pending
Both tegafur and, separately, 5-FU were exposed in a two-compartment HµREL® device containing hepatocytes cultured in the liver compartment and colon cancer cells cultured in the “target tissue” compartment. For comparison, both compounds were also tested on colon cancer cells using a conventional, static cell-based assay with no liver cells present.
With the HµREL® system, both tegafur and 5-FU were found to be cytotoxic to colon cancer cells in a dose-dependent fashion. However, tegafur was ineffective when tested using the traditional static assay. Moreover, HµREL® demonstrated cytotoxicity much more strongly with either compound than the static assay did with 5-FU. This confirmed that recirculation of the drug-containing culture medium through HµREL®’s liver compartment biotransformed tegafur into 5-FU.
Eric Novik, PhD
Ron White, White Global Pharma Consultants,LLCClarinex®: The Hunt for the Unproducible Metabolite