Mycophenolic acid sodium is a potent uncompetitive inhibitor of inosine monophosphate dehydrogenase (IMPDH), exhibiting an EC50 of 0.24 μM. It has broad antiviral activity against RNA viruses, including influenza. Additionally, mycophenolic acid sodium possesses immunosuppressive properties and exerts antiangiogenic and antitumor effects [1][2].

Mycophenolic acid sodium demonstrates antiviral effects against a wide range of RNA viruses including influenza, dengue virus, Zika virus, rotavirus, CCHFV, and hantavirus [1]. IMPDH is the rate-limiting enzyme in the de novo synthesis of guanosine nucleotides [2]. Mycophenolic acid (0.01-1 μM; 72 hours) sodium exhibits preferential antiproliferative activity against the endothelial cells and fibroblasts. Endothelial cells are most sensitive cells to Mycophenolic acid treatment with an IC 50 <500 nM for antimitotic effects [2]. Fibroblasts are also prone to Mycophenolic acid-induced cell cycle inhibition but exhibit a higher IC 50 (<1 μM) compared with endothelial cells. The two human tumor cell lines A549 non-small cell lung cancer cells and PC3 prostate cancer cells show intermediate sensitivity with an IC 50 >1 μM. U87 glioblastoma cells are resistant against Mycophenolic acid sodium treatment up to 1 μM [2]. Mycophenolic acid (0.05-2 μM; 18 hours) sodium exhibits a dose-dependent down-regulation of HDAC2 and MYC, whereas up-regulates NDRG1 [2]. Cell Proliferation Assay [2] Cell Line: Primary isolated human dermal microvascular endothelial cells (HDMVEC), fibroblasts, U87 glioblastoma cells, PC3 prostate cancer cells, A549 non-small cell lung cancer cells. Concentration: 0.01, 0.1, 1 μM Incubation Time: 72 hours Result: Exhibited preferential antiproliferative activity against HDMVEC and fibroblasts. Whereas U87 glioblastoma cells were resistant to treatment, A549 non-small cell lung cancer and PC3 prostate cancer cells showed intermediate sensitivity. Western Blot Analysis [2] Cell Line: HDMVEC Concentration: 0, 0.05, 0.1, 0.5, 1, and 2 μM Incubation Time: 18 hours Result: Showed a dose-dependent regulation of HDAC2, MYC, and NDRG1.

Mycophenolic acid (120 mg/kg; oral gavage; b.i.d.) sodium exerts its antitumor effects via modulation of the tumor microenvironment, U87 tumor growth is markedly inhibited in vivo in BALB/c nude mice [2]. Animal Model: Athymic 8-week-old, 20 g BALB/c nu/nu mice bearing Mycophenolic acid-resistant human U87 tumor model [2] Dosage: 120 mg/kg MMF (the morpholinoethyl ester prodrug of Mycophenolic acid) Administration: Oral gavage; b.i.d. Result: MMF (the morpholinoethyl ester prodrug of Mycophenolic acid) significantly inhibited tumor growth (～70% after day 14 after tumor implantation) in MMF-treated versus control mice. Microvessel density (CD31 staining) and pericyte coverage determined by α-smooth muscle actin staining were markedly reduced in MMF-treated versus control tumors (44% and 78%, respectively).