The coumarin derivative 4-methylumbelliferone (4MU, also known as hymecromone) is clinically approved in Europe and Asia for the treatment of biliary spasm. Despite its choleretic and spasmolytic properties, the poor pharmacokinetics of 4MU (short half-life and low oral bioavailability) limit its utility outside the biliary tract. 4MU is extensively metabolized to its glucuronic acid and sulfate forms by UDP-glucuronosyltransferases and is excreted into the intestine via enterohepatic circulation. available now

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At the doses consumed as a dietary supplement in mice and humans, 4MU exhibits potent antitumor activity due to its ability to inhibit hepatic hyaluronan (HA) synthesis. HA is the precursor of chondroitin sulphate proteoglycans, which form an important part of cell structures involved in a variety of processes, including inflammatory response, cell migration, cellular adhesion and signaling. 4MU attenuates HA synthesis by inhibiting the synthesis of hepatic HA synthases and depleting the availability of its precursor, uridine diphosphate (UDP)-glucuronic acid via the UDP-glucuronosyltransferase-mediated transfer to glucuronide or N-acetyl-glucosamine.

Moreover, in a preclinical model of TMZ resistance, combining 4MU with TMZ significantly enhanced its ability to overcome TMZ-resistant tumor cells. This observation suggests that the ability of 4MU to inhibit HA synthesis may provide a promising strategy for improving cancer therapy.

Rats were fed ad libitum with chocolate-flavoured chow (placebo) or chow containing 1.2 g/kg/4MU (MUM, DbPharma France) for 10 weeks. Blood samples were collected before and after the 10 week 4MU treatment period. Proteins that exceeded physiological values were observed in both the 4MU-treated and washout groups.