Mycophenolic acid

Mycophenolic acid is a potent uncompetitive inosine monophosphate dehydrogenase (IMPDH) inhibitor with an EC₅₀ of 0.24 µM. Mycophenolic acid demonstrates antiviral effects against a wide range of RNA viruses including influenza. Mycophenolic acid is an immunosuppressive agent. Antiangiogenic and antitumor effects^[1][2]. IC50 & Target: Mycophenolic acid (MPA) is an immunosuppressant drug used to prevent rejection in organ transplantation. It inhibits an enzyme needed for the growth of T cells and B cells. Mycophenolic acid (MPA) did not block the initial phase of viral translation but did interfere with viral protein synthesis in the amplification phase. Quantitative RT-PCR demonstrated that MPA prevented the accumulation of viral positive- and negative-strand RNA as the infection proceeded. Mycophenolic acid (MPA) inhibits flavivirus infection by preventing synthesis and accumulation of viral RNA^[1]. The effects of Mycophenolic acid (MPA) on DEN replication in monkey kidney (LLC-MK2) cells were examined. MPA (IC₅₀=0.4+/-0.3 microM) inhibited DEN2 replication. Quantitative real-time RT-PCR of viral RNA and plaque assays of virions from DEN2-infected and Mycophenolic acid (MPA) (10 microM) -treated cells showed a fivefold increase in defective viral RNA production by cells treated with each drug. suggesting that one mode of antiviral action of MPA is by inhibition of inosine monophosphate dehydrogenase and thereby depletion of the intracellular GTP pool^[2]. In Vitro: Mycophenolic acid 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) exhibits preferential antiproliferative activity against the endothelial cells and fibroblasts. Endothelial cells are most sensitive cells to Mycophenolic acid treatment with an IC₅₀ <500 nM for antimitotic effects^[2].
Fibroblasts are also prone to Mycophenolic acid-induced cell cycle inhibition but exhibit a higher IC₅₀ (<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 IC₅₀ >1 μM. U87 glioblastoma cells are resistant against MPA treatment up to 1 μM^[2].
Mycophenolic acid (0.05-2 μM; 18 hours) exhibits a dose-dependent down-regulation of HDAC2 and MYC, whereas up-regulates NDRG1^[2]. In Vivo: Mycophenolic acid exerts its antitumor effects via modulation of the tumor microenvironment, U87 tumor growth is markedly inhibited in vivo in BALB/c nude mice^[2].