hyaluronic acid (HA) synthesis inhibitor
Sample solution is provided at 25 µL, 10mM.
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|Description||4-Methylumbelliferone(4-MU) is an inhibitor of hyaluronic acid (HA) synthesis with an IC50 value of 0.4 mM.|
|Cas No.||90-33-5||SDF||Download SDF|
|Solubility||≥8.8mg/mL in DMSO||Storage||Desiccate at -20°C|
|Physical Appearance||A solid||Shipping Condition||Evaluation sample solution : ship with blue ice.All other available size: ship with RT , or blue ice upon request|
|General tips||For obtaining a higher solubility , please warm the tube at 37 ℃ and shake it in the ultrasonic bath for a while.Stock solution can be stored below -20℃ for several months.|
IC50: 0.4 mM
4-Methylumbelliferone is a hyaluronic acid (HA) synthesis inhibitor. The activation of HAS2 and the over-production of HA are existed in many metastatic tumor cell lines. Increased synthesis of HA is often associated with increased metastatic potential and invasivity in tumor cells.
In vitro: 4-Methylumbelliferone (MU), an inhibitor of HA synthesis, has been studied as a potential anti-tumor drug on account of inhibiting the growth of primary tumors and distant metastasis of tumor cells. The mechanism still needs to be clarified, although several studies revealed that the anticancer effects of MU are mediated by inhibition of HA signal pathway. In a previous study the regulation of HA synthesis was demonstrated by ceramide, and now show how MU activated NSMase2 generates ceramides and mediates MU modulated inhibition of HA synthesis (cell migration and invasion, and apoptosis of tumor cells). Using a HA enriched mouse oligodendroglioma cell line G26-24, it was found that MU elevated the activity of NSMase2 and enhanced ceramide levels, which in turn potentiated phosphatase PP2A activity. Further, the activated PP2A decreased phosphorylation of Akt, reduced activities of HA synthase2 (HAS2) and calpains, and blocked both the synthesis of HA, and the migration and invasion of G26-24 tumor cells. In addition, MU mediated ceramide induced activation of p53 and caspase-3, decreased SIRT1 expression and deduced G26-24 viability. The mechanism of the MU anticancer therefore initially involves NSMase2/ceramide/PP2A/AKT/HAS2/caspase-3/p53/SIRT1 and the calpain signaling pathway, indicating that ceramides play a important role in the ability of a tumor to become aggressively metastatic and grow .
In vivo: So far, no study in vivo has been conducted.
Clinical trial: Clinical study has been conducted.
 Qin J, Kilkus J, Dawson G. The hyaluronic acid inhibitor 4-methylumbelliferone is an NSMase2 activator-role of Ceramide in MU anti-tumor activity. Biochim Biophys Acta. 2016 Feb;1861(2):78-90.