Mycophenolate mofetil

2 years -80 in solvent

Administered via i.v.

ConA-stimulated T cells and LPS-stimulated B cells

0 to 10 uM

Mycophenolate mofetil is dissolved in 0.5% methylcellulose water.

Mycophenolate mofetil is an ester prodrug of the active immunosuppressant mycophenolic acid (MPA). The latter shows a, noncompetitive, selective and reversible inhibition activity against, inosine monophosphate dehydrogenase type I/II with IC50 of 39 nM and 27 nM, respectively. Moreover, MPA also produces the concentration-dependent inhibition of proliferation of ConA-stimulated T cells, LPS-stimulated B cells and alloantigen-specific T cells with IC50 of 100 nM, 120 nM, and 51 nM, respectively. [1], Mycophenolate mofetil with high concentration of 10 ug/mL induces a strong apoptosis in microglial cell cultures and increases the number of activated caspase-3 immunoreactive apoptotic cells. In addition, , Mycophenolate mofetil (1 ug/mL) strongly inhibits proliferation of both microglial cells and astrocytes. [2], A recent study shows that Mycophenolate mofetil significantly attenuates the extent of neuronal cell death of organotypic hippocampal slice cultures after neuronal injury in a time-dependent manner. [4]

48 hours

The spleens of male Lewis rats aged 8 weeks are aseptically removed and teased into single-cell suspensions, and the resulting splenocytes are suspended in RPMI1640 medium containing 10% fetal calf serum, 100 U/mL penicillin, and 100 ug/mL streptomycin. Assays are performed in flat-bottomed microtiter plates, with each well containing 150000 splenocytes in a total volume of 100 uL. Splenocytes are incubated in medium containing either 1 ug/mL Concanavalin A (ConA) or lipopolysaccharide (LPS) as T or B cell mitogen, respectively, along with various concentrations of MPA at 37 C for 48 hours in a humidified atmosphere of 5% CO2–95% air. During the final 6 hours of incubation, cells are pulsed with 1 uCi of 3H-thymidine/well, and harvested onto pressed fiberglass in a cell harvester. The uptake of 3H-thymidine by proliferating cells is measured using a liquid scintillation counter. The in vitro immune response of alloantigen-specific T cells is evaluated as a proliferation response using one-way mixed lymphoce reaction assay. Mesenteric lymph nodes cells from male Lewis rats aged 8 weeks and splenocytes from male ACI rats aged 8 weeks are used as responder and stimulator cells, respectively. Single-cell suspensions are prepared, and the responder cells are cultured with irradiated (20 Gy) stimulator cells in RPMI1640 supplemented with 10% fetal calf serum, 100 U/mL penicillin and 100 ug/mL streptomycin, in 96-well plates (U-bottom) and in the presence of various concentrations of, MPA (total volume: 200 uL, 37 C, 5% CO2 humidified atmosphere, 72 hours). As a negative control, responder cells are cultured with irradiated splenocytes of Lewis rats. The cell proliferation is quantified by the uptake of 3H-thymidine.

Mycophenolate mofetil is a non-competitive, selective and reversible inhibitor of inosine monophosphate dehydrogenase I/II with IC50 of 39 nM and 27 nM, respectively. Mycophenolate Mofetil induces caspase-dependent apoptosis and cell cycle inhibition in multiple myeloma cells.